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Testing the Addition of Anti-cancer Drug, ZEN003694, to the Usual Chemotherapy Treatment, Cetuximab Plus Encorafenib, for Colorectal Cancer
ctrrecruit@vcu.edu
NCT06102902
Inclusion Criteria:
* Patients must have histologically confirmed and radiographically measurable metastatic colorectal adenocarcinoma with known BRAF V600E mutation, confirmed in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory with at least one tumor measurable as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and for which standard curative or palliative measures do not exist or are no longer effective
* Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of ZEN003694 in combination with cetuximab and encorafenib in patients \< 18 years of age, children are excluded from this study
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
* Absolute neutrophil count ≥ 1,500/mcL
* Platelets ≥ 100,000/mcL
* Hemoglobin (Hb) ≥ 9 mg/dl
* Total bilirubin ≤ 1.5 mg/dl (excluding Gilbert's disease)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) ≤ 3 x institutional upper limit of normal (ULN)
* Creatinine clearance (CrCL) glomerular filtration rate (GFR) ≥ 50 mL/min/1.73 m\^2
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. Patients should be New York Heart Association Functional Classification of class II or better
* Patients must have progressed after at least 1 prior systemic treatment for incurable advanced or metastatic disease
* Patients must have received prior treatment with the combination of encorafenib and cetuximab. They must have tolerated the combination at doses planned for the study
* For the dose expansion phase, patients must have discontinued encorafenib at least 2 weeks prior to starting study treatment
* The effects of ZEN003694 on the developing human fetus are unknown. For this reason and because BRD and BET inhibitor agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for at least 4 months following the last dose of study drug. Women must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 72 hours prior to the start of investigational product. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants
Exclusion Criteria:
* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia
* Patients who are receiving any other investigational agents
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to ZEN003694 or other agents used in study
* Patients with uncontrolled intercurrent illness including, but not limited to, active bleeding diatheses, poorly controlled infection/disorders, or nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy
* Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 or substrates of CYP1A2 with narrow therapeutic windows are ineligible. Strong inhibitors or inducers of CYP3A4 must be discontinued at least 7 days prior to the first dose of ZEN003694. As proton pump inhibitors (PPIs), H2 receptor antagonists, and antacids may alter the pharmacokinetics of ZEN003694 by reducing ZEN003694 exposure, patients receiving proton pump inhibitors are ineligible. If H2 blockers or other acid reducing agents are used concomitantly with ZEN003694, a staggered dosing schedule should be used, either dose ZEN003694 2 hours before the H2 blocker or 10-12 hours after an H2 blocker. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
* Pregnant women are excluded from this study because ZEN003694 is BRD and BET inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ZEN003694, breastfeeding should be discontinued if the mother is treated with ZEN003694. These potential risks may also apply to other agents used in this study DRUG: BET Bromodomain Inhibitor ZEN-3694, PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, BIOLOGICAL: Cetuximab, PROCEDURE: Computed Tomography, PROCEDURE: Echocardiography Test, DRUG: Encorafenib, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Multigated Acquisition Scan
Metastatic Colorectal Adenocarcinoma, Recurrent Colorectal Adenocarcinoma, Refractory Colorectal Adenocarcinoma, Stage IV Colorectal Cancer AJCC v8
A Study of Sacituzumab Tirumotecan (MK-2870) as a Single Agent and in Combination With Pembrolizumab (MK-3475) Versus Treatment of Physician's Choice in Participants With HR+/HER2- Unresectable Locally Advanced or Metastatic Breast Cancer (MK-2870-010)
Toll Free Number - Trialsites@msd.com
NCT06312176
Inclusion Criteria:
* Has unresectable locally advanced or metastatic centrally-confirmed hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer
* Has radiographic disease progression on one or more lines of endocrine therapy for unresectable locally advanced/metastatic HR+/HER2- breast cancer, with one in combination with a CDK4/6 inhibitor
* Is a chemotherapy candidate
* Has an eastern cooperative oncology group (ECOG) performance status of 0 to 1 assessed within 7 days before randomization
* Has adequate organ function
* Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy
* Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received HBV antiviral therapy for at least 4 weeks, and have undetectable HBV viral load
* Participants with a history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable
Exclusion Criteria:
* Has breast cancer amenable to treatment with curative intent
* Has experienced an early recurrence (\<6 months after completing adjuvant/neoadjuvant chemotherapy) and therefore is eligible to receive second-line (2L) treatment
* Has symptomatic advanced/metastatic visceral spread at risk of rapidly evolving into life-threatening complications
* Has received prior chemotherapy for unresectable locally advanced or metastatic breast cancer
* Active autoimmune disease that has required systemic treatment in the past 2 years
* History of (noninfectious) pneumonitis/interstitial lung disease that requires steroids, or has current pneumonitis/interstitial lung disease
* Has an active infection requiring systemic therapy DRUG: Sacituzumab tirumotecan, BIOLOGICAL: Pembrolizumab, DRUG: Paclitaxel, DRUG: Nab-paclitaxel, DRUG: Capecitabine, DRUG: Liposomal doxorubicin
Breast Neoplasms
Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
Testing the Addition of an Anti-cancer Drug, Lenalidomide, to the Usual Combination Chemotherapy Treatment ("EPOCH") for Adult T-Cell Leukemia-Lymphoma (ATLL)
ctrrecruit@vcu.edu
NCT04301076
Inclusion Criteria:
* Patients must have histologically or cytologically confirmed CD2+, CD3+, or CD4+ acute, lymphoma or poor-risk chronic subtypes of ATLL including previously untreated or previously treated individuals who have received no more than 1 previous cycle of EPOCH, cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP), or cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide (CHOPE)
* Patients previously treated with azidothymidine (AZT), interferon (IFN), bexarotene, or mogamulizumab are eligible. Patients with stable disease at high risk of relapse from prior non-combination chemotherapy containing treatment are eligible to participate
* Documentation of HTLV infection by enzyme-linked immunosorbent assay (ELISA) in individuals with confirmation of HTLV-1 infection (by immunoblot or polymerase chain reaction \[PCR\]) or a consistent clinical picture (including two of three of: 1) CD4+ leukemia or lymphoma, 2) hypercalcemia, and/or 3) Japanese, Caribbean, or South American birthplace) is required for enrollment. Confirmation of HTLV-1 infection is required to continue the subject on protocol after the first cycle of therapy. Patients will be enrolled based on reports from local or referral labs (e.g., Mayo Clinic or LabCorp). Confirmation will be performed by Ratner Lab at Washington University, retrospectively, but this is not a Clinical Laboratory Improvement Amendments (CLIA) assay and is not reimbursed by insurance
* Age ≥ 18 years
* Because no dosing or adverse event (AE) data are currently available on the use of lenalidomide in combination with EPOCH in patients \< 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
* Absolute neutrophil count \>= 1,000/mm\^3 unless decreased due to bone marrow (BM) involvement with lymphoma
* Platelets \>= 100,000/mm\^3 unless decreased due to BM involvement with lymphoma
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN), if potentially due to lymphoma, in the dose-expansion cohort, the first cycle may be given without lenalidomide and if transaminitis and bilirubinemia improves to meet parameters, participant may be enrolled
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2 x institutional ULN, if potentially due to lymphoma, in the dose-expansion cohort, the first cycle may be given without lenalidomide and if transaminitis and bilirubinemia improve to meet parameters, participant may be enrolled
* Creatinine =\< institutional ULN OR glomerular filtration rate (GFR) \>= 60 mL/min/1.73 m\^2 for participants with creatinine levels above institutional normal
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
* Patients must have a life expectancy \> 12 weeks
* Patients must have no serious active infection requiring therapy at the time of study entry
* Patients must not require the concurrent use of chemotherapy, interferon, zidovudine, arsenic, radiation therapy, or other specific anti-tumor therapy, during the course of this study
* The effects of lenalidomide on the developing human fetus are unknown. Immunodulatory derivative (immunomodulatory imide drug \[IMiD\]) agents as well as other therapeutic agents used in this trial are known to be teratogenic. Females of child-bearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days prior to, and again within 24 hours of starting lenalidomide, and must either commit to continued abstinence from heterosexual intercourse or begin two acceptable methods of birth control, one highly effective method and one additional effective method at the same time, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. All patients must be counselled at a minimum of every 28 days about pregnancy precautions and risk of fetal exposure. Should a woman become pregnant or suspect she is pregnant while she or her partner are participating in this study, she should inform her treating physician immediately. FCBP must use adequate contraception for at least 28 days after discontinuation from study. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for at least 28 days after discontinuation from study
* Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally-authorized representative (LAR) and/or family member available will also be eligible
Exclusion Criteria:
* Patients that have received prior IMiDs for treatment of ATLL
* Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
* Patients who have not recovered to grade 1 or better from AEs due to prior anti-cancer therapy (not including cycle 1 of EPOCH, CHOP, or CHOPE if received off protocol) within 14 days prior to enrollment, with the exception of alopecia
* Patients who are receiving any other investigational agents or have received them within 14 days prior to enrollment
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to lenalidomide or other agents used in study. Anaphylactic reactions including death have been reported with cyclophosphamide. Possible cross-sensitivity with other alkylating agents can occur
* Patients unable to take aspirin or prophylactic doses of low molecular weight heparin or direct oral anticoagulants
* Patients with urinary outflow obstruction (contraindication for cyclophosphamide)
* Patients with any form of demyelinating disease should not be given vincristine sulfate injection
* Patients with uncontrolled intercurrent illness
* Patients with psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant women are excluded from this study because lenalidomide is an IMiD agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with lenalidomide, breastfeeding should be discontinued if the mother is treated with lenalidomide. These potential risks may also apply to other agents used in this study PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Biopsy, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, DRUG: Doxorubicin Hydrochloride, PROCEDURE: Echocardiography Test, DRUG: Etoposide, DRUG: Lenalidomide, PROCEDURE: Multigated Acquisition Scan, PROCEDURE: Positron Emission Tomography, DRUG: Prednisone, DRUG: Vincristine Sulfate
Acute Adult T-Cell Leukemia/Lymphoma, Adult T-Cell Leukemia/Lymphoma, Chronic Adult T-Cell Leukemia/Lymphoma, HTLV-1 Infection
Testing Olaparib for One or Two Years, With or Without Bevacizumab, to Treat Ovarian Cancer
ctrrecruit@vcu.edu
NCT06580314
Inclusion Criteria:
* Patients with newly diagnosed, pathologically confirmed, Federation of Gynecology and Obstetrics (FIGO) stage III or IV ovarian cancer of the following types:
* High grade serous
* High grade endometrioid (excluding tumors that are known mismatch repair deficient/microsatellite instability high (MMR-D/MSI-H) or POLE ultramutated)
* Carcinosarcoma (excluding tumors that are known mismatch repair deficient/microsatellite instability high (MMR-D/MSI-H) or POLE ultramutated), and/or
* Other epithelial ovarian cancer with BRCA1/2 deleterious alteration (germline or somatic), (excluding tumors that are known mismatch repair deficient/microsatellite instability high (MMR-D/MSI-H) or POLE ultramutated)
* Submission of pathology report is required
* Ovarian cancer = ovarian, fallopian, or primary peritoneal cancer
* Patients must have:
* Documented variant (tumor or germline) in BRCA1 or BRCA2 that is predicted to be pathogenic or suspected pathogenic (deleterious alteration)
* Submission of testing report is required. OR
* BRCA 1/2 wildtype AND known HRD deficient tumor determined by any commercial or academic, Clinical Laboratory Improvement Act (CLIA)-certified laboratory (e.g., Myriad MyChoice©)
* Submission of testing report is required
* Patient must have undergone cytoreductive surgery (primary or interval)
* Patients must have completed first line platinum-based therapy prior to registration:
* Platinum based chemotherapy course must have consisted of a minimum of 4 treatment cycles and a maximum of 9, although it is strongly recommended that patients receive at least 6 cycles unless medically contraindicated
* For those receiving less than 6 cycles of platinum-based therapy, the reason for this must be documented and could include hematologic toxicity or non-hematologic toxicities directly related to therapy
* Intravenous, intraperitoneal, or neoadjuvant platinum-based chemotherapy is allowed; for weekly therapy, three weeks are considered one cycle
* Patients must not have received an investigational agent during their first line course of chemotherapy
* Patients must have, in the opinion of the investigator, no clinical evidence of disease progression following completion of this chemotherapy course (partial or complete response to platinum-based chemotherapy)
* Patients with treated brain metastases are eligible if follow up brain imaging after central nervous system (CNS) directed therapy shows no evidence of progression and patients are neurologically stable off steroid therapy
* Patients must be randomized at least 3 weeks and no more than 12 weeks after their last dose of chemotherapy (last dose is the day of the last infusion of platinum agent)
* No previous treatment with a PARP inhibitor, including olaparib, niraparib, and rucaparib
* Age ≥ 18
* Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
* Not pregnant and not nursing
* Absolute neutrophil count (ANC) ≥ 1,500 cells/mm\^3
* Platelets ≥ 100,000 cells/mm\^3
* Hemoglobin ≥ 9 g/dl
* Creatinine clearance (CrCL) of \> 30 mL/min by the Cockcroft-Gault formula
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level ≤ 3 x institutional ULN may be enrolled)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x institutional ULN
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
* No active infection requiring parental antibiotic(s)
* No current evidence of intra-abdominal abscess, abdominal/pelvic fistula (not diverted), gastrointestinal perforation, gastrointestinal (GI) obstruction, and/or need for drainage nasogastric or gastrostomy tube
* No current inability to swallow orally administered medication
* No history of myelodysplastic syndrome and/or acute myeloid leukemia
* No history of allogeneic bone marrow transplant
* No concomitant use of strong or moderate CYP3A inducers
* No known hypersensitivity to olaparib or any of the excipients of the product BIOLOGICAL: Bevacizumab, PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, PROCEDURE: Magnetic Resonance Imaging, DRUG: Olaparib
Fallopian Tube Endometrioid Adenocarcinoma, Fallopian Tube High Grade Serous Adenocarcinoma, Fallopian Tube Malignant Mixed Mesodermal (Mullerian) Tumor, FIGO Stage III Ovarian Cancer 2014, FIGO Stage IV Ovarian Cancer 2014, Ovarian Carcinoma, Ovarian Carcinosarcoma, Ovarian High Grade Endometrioid Adenocarcinoma, Ovarian High Grade Serous Adenocarcinoma, Primary Peritoneal Carcinosarcoma, Primary Peritoneal Endometrioid Adenocarcinoma, Primary Peritoneal High Grade Serous Adenocarcinoma
A Study of First-Line Olomorasib (LY3537982) and Pembrolizumab With or Without Chemotherapy in Patients With Advanced KRAS G12C-Mutant Non-small Cell Lung Cancer (SUNRAY-01)
Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or - LillyTrials@Lilly.com
NCT06119581
Inclusion Criteria:
* Histologically or cytologically confirmed NSCLC with Stage IIIB-IIIC or Stage IV disease, not suitable for curative intent radical surgery or radiation therapy.
* Part B and Safety Lead-In Part B: the histology of the tumor must be predominantly non-squamous (in line with pemetrexed label).
* Must have disease with evidence of KRAS G12C mutation.
* Must have known programmed death-ligand 1 (PD-L1) expression
* Part A: Greater than or equal to (≥)50 percent (%).
* Part B: 0% to 100%.
* Part C: \<50%.
* Must have measurable disease per RECIST v1.1.
* Must have an ECOG performance status of 0 or 1.
* Estimated life expectancy ≥12 weeks.
* Ability to swallow capsules.
* Must have adequate laboratory parameters.
* Contraceptive use should be consistent with local regulations for those participating in clinical studies.
* Women of childbearing potential must
* Have a negative pregnancy test.
* Not be breastfeeding during treatment
Exclusion Criteria:
* Have a documented additional validated targetable oncogenic driver mutation or alteration in genes such as epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), BRAF (V600E), human epidermal growth factor receptor 2 (HER2), MET (exon 14), ROS1, rearranged during transfection (RET), or neurotrophic tyrosine receptor kinase (NTRK)1/2/3.
* Have had any of the following prior to randomization:
\-- Prior systemic therapy (chemotherapy, immunotherapy, targeted therapy, or biological therapy) for advanced or metastatic NSCLC.
\--- 1 cycle of standard-of-care treatment prior to study enrollment will be allowed for cases where immediate treatment is clinically indicated:
* Have known active central nervous system metastases and/or carcinomatous meningitis.
Exclusion Criteria for Participants receiving Pemetrexed and Platinum (Part B and Safety Lead-In Part B)
* Have predominantly squamous cell histology for NSCLC
* Only for participants with mild to moderate renal insufficiency: Unable to avoid aspirin, ibuprofen, or other nonsteroidal anti-inflammatory drugs (NSAIDs) two days before (5 days for long acting NSAIDs), day of, and two days after administration of pemetrexed
* Is unable or unwilling to take folic acid or vitamin B12 supplementation. DRUG: LY3537982, DRUG: Pembrolizumab, DRUG: Placebo, DRUG: Cisplatin, DRUG: Carboplatin, DRUG: Pemetrexed
Carcinoma, Non-Small-Cell Lung, Neoplasm Metastasis
Advanced Non-Small Cell Lung Cancer, KRAS G12 Lung Cancer, Advanced Lung Cancer, Metastatic Lung Cancer, KRAS G12C inhibitor, KRAS G12C Positive, KRAS Mutation, KRAS G12 Mutation, Lung Cancer Mutation, Olomorasib, Lung Diseases, Neoplastic Processes, Pathologic Processes, Neoplasm Metastasis, Non-Small Cell Lung Cancer, Non-Small Cell Lung Cancer (NSCLC), Antineoplastic Agents, Respiratory Tract Neoplasms, Thoracic Neoplasms, Neoplasms by Site, Neoplasms, Respiratory Tract Diseases, Carcinoma, Bronchogenic, Bronchial Neoplasms, Lung Neoplasms
Reaching Rural Cancer Survivors Who Smoke Using Text-Based Program
Devon Noonan, PhD, MPH, FNP-BC - devon.noonan@duke.edu
NCT05008848
Inclusion Criteria:
* Have a cancer diagnosis within the past 10 years
\* Note: Patients with ductal carcinoma in situ (DCIS) are eligible and patients currently receiving curative treatment are eligible
* Not currently on hospice
* Currently smokes \>= 5 cigarettes daily
\* Note: Participants who smoke cigarettes and vape are eligible. Those who only vape are ineligible
* Lives in a nonmetro/rural county (defined as having a Rural Urban Continuum Code \[RUCC\] code of 4-9) and/or a Rural-Urban Commuting area code of 4-10 and/or as defined by the Office of Management and Budget as a non-rural county large area metro census tracts of at least 400 square miles in an area with population density of 35 or less per square mile with rural-urban commuting area (RUCA) codes 2-3; and outlying metro counties without a UA. The RUCC code and RUCA (4-10) codes can be checked at: https://www.ruralhealthinfo.org/am-i-rural. Those with RUCA codes of 2-3 can be checked at https://data.hrsa.gov/tools/rural-health for eligibility
* Patient interested in participating in a smoking cessation program, and not currently participating in a smoking cessation clinical trial
* Not currently using any smoking cessation pharmacotherapy (e.g. nicotine replacement therapy, bupropion or varenicline for smoking purposes only), or currently participating in any cessation program at the time of enrollment
* Patient has a cell phone or smart phone device with texting ability
* In order to complete the mandatory patient-completed measures, participants must be able to speak and read English or Spanish
* Age \>= 18 years
* Participant must be willing to provide a urine sample.
* Patients with impaired decision-making capacity are not eligible for this study consent BEHAVIORAL: Smoking Cessation Intervention, OTHER: Health Promotion and Education, OTHER: Informational Intervention, OTHER: Questionnaire Administration
Cigarette Smoking-Related Carcinoma
Safety and Tolerability Study of ST-503 for Refractory Pain Due to Peripheral Neuropathy (Small Fiber Predominant, SFN)
Patient Advocacy - clinicaltrials@sangamo.com
NCT06980948
Inclusion Criteria
• Diagnostic characterization of Small Fiber Neuropathy (SFN) according to the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities and Networks (ACTTION) criteria.
• Medical record documentation that pain is refractory to 2 of 3 categories of first line medical therapy for at ≥ 6 months prior to screening.
• Serum sample negative for pre-existing anti-AAV9 antibodies determined by assay detection limit Exclusion Criteria
• Drug- and alcohol-related:
• Persons using opioid analgesics for under 3 months or persons who are not on a stable dose of opioids; if on a stable dose, the dose may decrease over the course of the study but should not be increased.
• History of known alcohol abuse, opioid analgesic abuse, or illicit drug abuse within 2 years of Screening.
• Positive urine test for drugs of abuse (including opiates, benzodiazepines, amphetamines, cocaine, barbiturates, and phencyclidine) without prescription and investigator approval, at Screening and Day -1.
• Use of cannabinoids is not permitted.
• Persons with Fabry's disease, with erythromelalgia, with peripheral neuropathies due to alcohol or drug toxicity, or with diagnosed channelopathies
• Procedure-related:
• Contraindications to LP, general anesthesia or sedation
• Any medical disorders that, in the opinion of the Investigator, could interfere with LP including but not limited to evidence for a pressure gradient between supratentorial and infratentorial compartments, Arnold-Chiari malformation, bleeding diathesis, clinically significant coagulopathy, thrombocytopenia, increased intracranial pressure, or spine disease or past surgical procedures involving the spine
• Infectious disease-related:
• Active viral infection or bacterial
• A severe infection (e.g., pneumonia, septicemia, central nervous system infections \[e.g., meningitis, encephalitis\]) within 12 weeks prior to Screening
• Hepatic disease- and hepatotoxic medication-related:
• Presence of clinically relevant liver disease
• Hepatic dysfunction as indicated by one or more of the following: i. Albumin ≤ 3.5 g/dL ii. Total bilirubin \> 1.5 x ULN and direct bilirubin ≥0.5 mg/dL iii. Alkaline phosphatase (ALP) \> 2 x ULN iv. Alanine transaminase (ALT) or aspartate transaminase (AST) \> 1.5 x ULN
• Hepatotoxic medications should be avoided during the study period including acetaminophen exceeding 4 gm/day unless essential to patient's treatment, approved by investigator, and hepatic dysfunction is not identified
• Hepatotoxic supplement use during the study period
• Cancer-related: a. History of cancer, including B-cell cancers, within 5 years of Screening i. Exceptions to this exclusion are fully excised non-melanoma skin cancers, non-metastatic prostate cancer, and fully treated ductal carcinoma in situ of the breast, provided subject has been stable for at least 6 months b. Previous autologous or allogeneic bone marrow transplant, peripheral stem cell transplant or solid organ transplantation
• Previously received gene or cellular therapy
• Diagnostic characterization of Small Fiber Neuropathy (SFN) according to the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities and Networks (ACTTION) criteria.
• Medical record documentation that pain is refractory to 2 of 3 categories of first line medical therapy for at ≥ 6 months prior to screening.
• Serum sample negative for pre-existing anti-AAV9 antibodies determined by assay detection limit Exclusion Criteria
• Drug- and alcohol-related:
• Persons using opioid analgesics for under 3 months or persons who are not on a stable dose of opioids; if on a stable dose, the dose may decrease over the course of the study but should not be increased.
• History of known alcohol abuse, opioid analgesic abuse, or illicit drug abuse within 2 years of Screening.
• Positive urine test for drugs of abuse (including opiates, benzodiazepines, amphetamines, cocaine, barbiturates, and phencyclidine) without prescription and investigator approval, at Screening and Day -1.
• Use of cannabinoids is not permitted.
• Persons with Fabry's disease, with erythromelalgia, with peripheral neuropathies due to alcohol or drug toxicity, or with diagnosed channelopathies
• Procedure-related:
• Contraindications to LP, general anesthesia or sedation
• Any medical disorders that, in the opinion of the Investigator, could interfere with LP including but not limited to evidence for a pressure gradient between supratentorial and infratentorial compartments, Arnold-Chiari malformation, bleeding diathesis, clinically significant coagulopathy, thrombocytopenia, increased intracranial pressure, or spine disease or past surgical procedures involving the spine
• Infectious disease-related:
• Active viral infection or bacterial
• A severe infection (e.g., pneumonia, septicemia, central nervous system infections \[e.g., meningitis, encephalitis\]) within 12 weeks prior to Screening
• Hepatic disease- and hepatotoxic medication-related:
• Presence of clinically relevant liver disease
• Hepatic dysfunction as indicated by one or more of the following: i. Albumin ≤ 3.5 g/dL ii. Total bilirubin \> 1.5 x ULN and direct bilirubin ≥0.5 mg/dL iii. Alkaline phosphatase (ALP) \> 2 x ULN iv. Alanine transaminase (ALT) or aspartate transaminase (AST) \> 1.5 x ULN
• Hepatotoxic medications should be avoided during the study period including acetaminophen exceeding 4 gm/day unless essential to patient's treatment, approved by investigator, and hepatic dysfunction is not identified
• Hepatotoxic supplement use during the study period
• Cancer-related: a. History of cancer, including B-cell cancers, within 5 years of Screening i. Exceptions to this exclusion are fully excised non-melanoma skin cancers, non-metastatic prostate cancer, and fully treated ductal carcinoma in situ of the breast, provided subject has been stable for at least 6 months b. Previous autologous or allogeneic bone marrow transplant, peripheral stem cell transplant or solid organ transplantation
• Previously received gene or cellular therapy
GENETIC: ST-503, PROCEDURE: Sham (No Treatment)
Chronic Neuropathic Pain
Small Fiber Neuropathy
Tailoring Therapy in Post-surgical Patients With Low-risk Endometrial Cancer
ctrrecruit@vcu.edu
NCT06388018
Inclusion Criteria:
* Patients must have had surgery consisting of hysterectomy (total abdominal, laparoscopic or robotic-assisted) and bilateral salpingo-oophorectomy. Lymph node dissection can be performed as per institutional standards (sentinel or full lymphadenectomy). There must be no macroscopic residual disease after surgery
* Patients must have histologically confirmed stage I to III endometrial carcinoma which can be endometrioid, serous, clear cell, un/dedifferentiated, carcinosarcoma or mixed
* Patients' Eastern Cooperative Group (ECOG) performance status must be 0, 1, or 2
* Patients' age must be \>= 18 years
* Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate. A similar process must be followed for sites outside of Canada as per their respective cooperative group's procedures
* Patient is able (i.e. sufficiently fluent) and willing to complete the patient reported outcomes (PRO) questionnaires in either English, French or a validated language. The baseline assessment must be completed within required timelines, prior to enrollment. Inability (lack of comprehension in English or French, or other equivalent reason such as cognitive issues or lack of competency) to complete the questionnaires will not make the patient ineligible for the study. However, ability but unwillingness to complete the questionnaires will make the patient ineligible
* Patients must be accessible for treatment and follow-up. Patients enrolled on this trial must be treated and followed at the participating centre. This implies there must be reasonable geographical limits placed on patients being considered for this trial. The patient's city of residence may be required to verify their geographical proximity. (Call the CCTG office (613-533-6430) if questions arise regarding the interpretation of this criterion.) Investigators must assure themselves the patients enrolled on this trial will be available for complete documentation of the treatment, adverse events, and follow-up
* Patients must agree to return to their primary care facility for any adverse events which may occur through the course of the trial
* Protocol treatment is to begin within 10 weeks of hysterectomy/bilateral salpingo-oophorectomy
* SUB-STUDY A: Patients with endometrial carcinoma (endometrioid, serous, clear cell, un-/dedifferentiated, carcinosarcoma, mixed), must have one of the following combinations of International Federation of Gynecology and Obstetrics (FIGO) stage, grade, and lymphovascular invasion (LVI):
* Cohort A1:
* Stage IA (not confined to polyp), grade 3, pN0, with or without LVI (Pelvic lymph node surgical assessment (sentinel or full lymphadenectomy) is required for grade 3 or stage II. Para-aortic lymphadenectomy is not mandated.)
* Stage IB, grade 1 or 2, pNx/N0, with or without LVI
* Stage IB, grade 3, pN0, without substantial LVI (Pelvic lymph node surgical assessment (sentinel or full lymphadenectomy) is required for grade 3 or stage II. Para-aortic lymphadenectomy is not mandated.)
* Stage II (microscopic), grade 1 or 2, pN0, without substantial LVI (Pelvic lymph node surgical assessment (sentinel or full lymphadenectomy) is required for grade 3 or stage II. Para-aortic lymphadenectomy is not mandated.) (Substantial LVI is defined as \>= 3 foci per College of American Pathologists' reporting guideline)
* Cohort A2:
* Stage IA (not confined to polyp), grade 3, pNx, with or without LVI
* Stage IB, grade 3, pNx, with or without LVI
* Stage IB, grade 3, pN0, with substantial LVI (Substantial LVI is defined as \>= 3 foci per College of American Pathologists' reporting guideline)
* Stage II (microscopic), grade 1 or 2, pNx, with or without LVI
* Stage II (microscopic), grade 1 or 2, pN0, with substantial LVIƒõ
* Stage II (microscopic), grade 3, pNx/N0, with or without LVI
* Stage II non-microscopic, any grade, pNx/N0, with or without LVI
* Stage III, any grade, pNx/N0-2, with or without LVI
* Substantial LVI is defined as .3 foci per College of American Pathologists¡¦ reporting guideline
* SUB-STUDY A: Patients must have a molecular classification of POLE mutation.
* Note: patients in Cohort A2 should have a known POLE pathogenic mutation prior to consenting
* SUB-STUDY B: Patients with endometrial carcinoma (endometrioid only), must have one of the following combinations of FIGO stage, grade, and lymphovascular invasion (LVI):
* Stage IA (not confined to polyp), grade 3, pN0, with or without LVI (Pelvic lymph node surgical assessment \[sentinel or full lymphadenectomy\] is required for grade 3 or stage II. Para-aortic lymphadenectomy is not mandated) (Substantial LVI is defined as \>= 3 foci per College of American Pathologists' reporting guideline)
* Stage IB, grade 1 or 2, pNx/N0, with or without LVI
* Stage IB, grade 3, pN0, without substantial LVI (Pelvic lymph node surgical assessment \[sentinel or full lymphadenectomy\] is required for grade 3 or stage II. Para-aortic lymphadenectomy is not mandated) (Substantial LVI is defined as \>= 3 foci per College of American Pathologists' reporting guideline)
* Stage II (microscopic), grade 1 or 2, pN0\*, without substantial LVI (Pelvic lymph node surgical assessment \[sentinel or full lymphadenectomy\] is required for grade 3 or stage II. Para-aortic lymphadenectomy is not mandated) (Substantial LVI is defined as \>= 3 foci per College of American Pathologists' reporting guideline)
* SUB-STUDY B: Patients must have molecular classification of p53wt/NSMP (based on normal p53 IHC, and absence of pathogenic POLE mutation or MMR deficiency)
* SUB-STUDY B: Estrogen receptor positive (\> 10% of the tumour with positive nuclear staining) on IHC
Exclusion Criteria:
* Prior neoadjuvant chemotherapy for current endometrial cancer diagnosis
* Prior pelvic radiation
* Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for \>= 5 years
* Clinical evidence of distant metastasis as determined by pre-surgical or post-surgical imaging (CT scan of chest, abdomen and pelvis or whole-body PET-CT scan)
* SUB-STUDY A: Isolated tumour cell(s) identified in lymph node(s) for patients in Cohort A1
* SUB-STUDY B: Abnormal p53 and/or mismatch repair deficiency on immunohistochemistry without pathogenic POLE mutation.
* Abnormal p53 can also be determined by TP53 mutations found on DNA testing.
* SUB-STUDY B: p53wt/NSMP endometrial carcinoma with a MELF (microcystic, elongated and fragmented) pattern of myoinvasion and/or substantial lymphovascular invasion
* SUB-STUDY B: Stage IA (not confined to polyp), grade 3, pN0, with substantial LVI. Stage IB, grade 1 or 2, pNx/N0, with substantial LVI
* SUB-STUDY B: Isolated tumour cell(s) identified in lymph node(s) OTHER: Clinical Observation, PROCEDURE: Computed Tomography, RADIATION: External Beam Radiation Therapy, PROCEDURE: High-Dose-Rate Vaginal Brachytherapy, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Positron Emission Tomography, OTHER: Questionnaire Administration, PROCEDURE: X-Ray Imaging
Stage I Uterine Corpus Endometrial Stromal Sarcoma AJCC v8, Stage II Uterine Corpus Endometrial Stromal Sarcoma AJCC v8, Stage III Uterine Corpus Endometrial Stromal Sarcoma AJCC v8
MYELOMATCH: A Screening Study to Assign People With Myeloid Cancer to a Treatment Study or Standard of Care Treatment Within myeloMATCH (MyeloMATCH Screening Trial)
ctrrecruit@vcu.edu
NCT05564390
Inclusion Criteria:
* Participants must be suspected to have previously untreated acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Participants with AML cannot have a history of previously treated myeloproliferative neoplasms (MPN) or MDS.
* Participants must be \>= 18 years of age.
* Participants must not have received prior anti-cancer therapy for AML or MDS.
* Note: Hydroxyurea to control the white blood cell count (WBC) is allowed.
* Note: Prior erythroid stimulating agent (ESA) is not considered prior therapy for the purposes of eligibility. Participants must not be currently receiving any cytarabine-containing therapy other than up to 1 g/m\^2 of cytarabine, which is allowed for urgent cytoreduction.
* Participants are allowed prior use of hydroxyurea, all-trans retinoic acid (ATRA), BCR-ABL directed tyrosine kinase inhibitor, erythropoiesis-stimulating agent, thrombopoietin receptor agonist and lenalidomide, with a maximum limit of 1 month of exposure.
* Note: Participants receiving hydroxyurea prior to treatment substudy or TAP assignment must agree to discontinue hydroxyurea within 24 hours before beginning substudy or TAP treatment.
* Participants must not have a prior or concurrent malignancy that requires concurrent anti-cancer therapy
* Note: active hormonal therapy is allowed
* Participants must have a Zubrod Performance Status evaluation within 28 days prior to registration.
* Participants must agree to have translational medicine specimens submitted.
* Participants must be offered the opportunity to participate in specimen banking.
* Note: Specimens must be collected and submitted following the initial paper-based process and subsequently via the Precision Medicine Specimen Tracking Forms in Medidata Rave instance for the MyeloMATCH MSRP.
* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines.
* Note: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.
* The master screening and reassessment protocol (MSRP) should only be used in sites where the relevant AML treatment substudies are open or if the site is willing to follow the MSRP Tier Advancement Pathway (TAP) for patients in the event that the site does not have the relevant study open and transfer to another site that does have the study open. For example, if a site does not have a myeloMATCH Tier 1 study for older AML open for enrollment, such older AML patients should only be consented for the MSRP if the site is willing to treat the patient with standard of care on TAP or is willing to transfer the patient to a center with a study open that the patient would otherwise match to. PROCEDURE: Allogeneic Hematopoietic Stem Cell Transplantation, DRUG: Azacitidine, DRUG: Azacitidine, OTHER: Best Practice, PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Bone Marrow Biopsy, DRUG: Busulfan, PROCEDURE: Chest Radiography, PROCEDURE: Computed Tomography, DRUG: Cytarabine, DRUG: Daunorubicin, DRUG: Daunorubicin Hydrochloride, DRUG: Decitabine and Cedazuridine, PROCEDURE: Echocardiography Test, BIOLOGICAL: Emavusertib, DRUG: Enasidenib, BIOLOGICAL: Epoetin Alfa, DRUG: Fludarabine, DRUG: Gemtuzumab Ozogamicin, DRUG: Gilteritinib, DRUG: Liposome-encapsulated Daunorubicin-Cytarabine, BIOLOGICAL: Luspatercept, DRUG: Melphalan, PROCEDURE: Multigated Acquisition Scan, PROCEDURE: Mutation Carrier Screening, DRUG: Olutasidenib, DRUG: Placebo Administration, PROCEDURE: Positron Emission Tomography, DRUG: Quizartinib, RADIATION: Total-Body Irradiation, DRUG: Venetoclax
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm, Acute Myeloid Leukemia Post Cytotoxic Therapy, Acute Myeloid Leukemia, Myelodysplasia-Related, Myelodysplastic Syndrome
Adding Nivolumab to Usual Treatment for People With Advanced Stomach or Esophageal Cancer, PARAMUNE Trial
ctrrecruit@vcu.edu
NCT06203600
Inclusion Criteria:
* Participants must have advanced or locally unresectable gastric, gastroesophageal junction or esophageal adenocarcinoma
* Participants must have PD-L1 CPS (Combined Positive Score) ≥ 1. This test would have been performed as part of standard of care (SOC) pathology testing, using tissue obtained within two years prior to registration and collected prior to or after a frontline regimen
* Participants must have a histologically confirmed diagnosis of microsatellite stable (MSS) and HER2 negative gastric, gastroesophageal junction, or esophageal adenocarcinoma
* Participants must have documented unresectable and/or metastatic disease on CT or MRI imaging completed prior to registration. Imaging must have been completed within 28 days prior to registration for participants with measurable disease. CT scans or MRIs used to assess non-measurable disease must have been completed within 42 days prior to registration. All disease must be assessed and documented on the Baseline Tumor Assessment Form
* Participants with treated brain metastases must have no evidence of progression on the follow-up brain imaging after central nervous system (CNS)-directed therapy. All treatment for brain metastases must have been completed at least 28 days prior to registration
* Participants must have disease progression or intolerance to frontline standard of care (SOC) chemotherapy plus either nivolumab, pembrolizumab or any other PD-1 or PD-L1 inhibitor. Peri-operative chemotherapy plus nivolumab, pembrolizumab or any other PD-1 or PD-L1 inhibitor will count as one line if disease progression occurs while on the therapy or within 6 months of completing the chemotherapy plus nivolumab or pembrolizumab or other PD-1/PD-L1 inhibitor cycle
* Participants must not have received more than one prior line of systemic therapy defined as chemotherapy plus either nivolumab, pembrolizumab, or any other PD-1 or PD-L1 inhibitor, in the stage IV or unresectable setting. Peri-operative or adjuvant nivoluamb or other PD-1/PD-L1 inhibitors would count as one prior line of systemic therapy if patients progressed while on nivolumab (or other PD-1/PD-L1 inhibitors) or within 6 months of stopping it
* Note: Radiation or any other regional therapy options done to address local residual disease or metastatic disease would not count as a line of therapy. Maintenance therapy with a different form of fluoropyrimidine (i.e. switching from capecitabine to fluorouracil \[5FU\]) would not count as another line of therapy
* Participants must not have a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of registration. Inhaled or topical steroids and adrenal replacement doses \< 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Participants are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if \< 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted, as long as there has been a washout period for corticosteroids of ≥ 7 days prior to registration
* Participants must not have prior significant immunotherapy related adverse events requiring permanent discontinuation of the immunotherapy agent including events like pneumonitis, myocarditis, renal failure, Guillain barre syndrome, or myasthenia gravis. Participants with endocrinopathy events leading or not to replacement steroids, thyroid hormone, insulin, or cortisol are eligible
* Participants must not have received a live attenuated vaccination within 28 days prior to registration
* Participants must not have had a major surgery within 28 days or subcutaneous venous access device placement within 7 days prior registration
* Participants must have fully recovered from the effects of prior surgery in the opinion of the treating investigator. Any participants with postoperative bleeding complications or wound complications from a surgical procedure performed in the last eight weeks should be excluded
* Participants must not have plans to undergo elective or planned major surgery during the clinical trial
* Participants must not have active bleeding or prior history of gastrointestinal (GI) perforation, fistula or significant GI bleeding (requiring transfusion, endoscopic or surgical intervention) within 84 days prior to registration
* Participants must not be planning to receive any concurrent chemotherapy, immunotherapy, investigational agents, biologic or hormonal therapy for cancer treatment while receiving treatment on this study
* Participants must not have a history of a grade 3 or 4 allergic reaction attributed to humanized or human monoclonal antibody therapy
* Participants must not have a history of grade 3 or 4 immunotherapy related toxicities with the exception of hormonal abnormalities like thyroiditis or thyroid derangements
* Participants must be ≥ 18 years old
* Participants must have Zubrod Performance Status of 0-2
* Participants must have a complete medical history and physical exam within 28 days prior to registration
* Leukocytes ≥ 2 x 10\^3/uL (within 28 days prior to registration)
* Absolute neutrophil count ≥ 1.2 x 10\^3/uL (within 28 days prior to registration)
* Hemoglobin ≥ 9.0 g/dL (within 28 days prior to registration)
* Platelets ≥ 100 x 10\^3/uL (within 28 days prior to registration)
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (within 28 days prior to registration) unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin ≤ 5 x institutional ULN
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 × institutional ULN (within 28 days prior to registration) (unless liver metastases are present, in which case they must be ≤ 5 x ULN)
* Participants must have a calculated creatinine clearance ≥ 40 mL/min using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to registration
* Participants' urinary protein must be ≤ 1+ on dipstick or routine urinalysis (UA) within 28 days of registration. Random analysis of urine protein with a normal value is sufficient. If urine dipstick or routine analysis indicated proteinuria ≥ 2+, then a 24-hour urine is to be collected and demonstrate \< 1000 mg of protein in 24 hours to allow participation in the study
* Participants must have adequate cardiac function. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2 or better
* Participants must have recovered to baseline or \< grade 2 CTCAE version (v) 5.0 from toxicities related to any prior treatments, unless AE(s) are clinically stable on supportive therapy
* Participants must not have experienced arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to registration
* Participants must not have uncontrolled blood pressure within 28 days prior to registration as determined by the treating investigator
* Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at registration and have undetectable viral load on the most recent test results obtained within 6 months prior to registration
* Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load while on suppressive therapy on the most recent test results obtained within 6 months prior to registration, if indicated
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load on the most recent test results obtained within 6 months prior to registration, if indicated
* Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen
* Participants must not be pregnant or nursing (nursing includes breast milk fed to an infant by any means, including from the breast, milk expressed by hand, or pumped). Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
* Participants must not have a history of inflammatory bowel disease, (including ulcerative colitis and Crohn's disease), symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune vasculitis \[e.g., Wegener's Granulomatosis\]); CNS or motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre Syndrome and myasthenia gravis, multiple sclerosis). Note: Participants with Graves' disease will be allowed
* Participants must not have a history of pneumonitis that has required oral or IV steroids within the last 12 months prior to registration
* Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System
* Participants who can complete patient reported outcomes (FACT-Ga and PRO-CTCAE) questionnaires in English or Spanish must participate in the quality of life studies
* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines. For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, PROCEDURE: Magnetic Resonance Imaging, BIOLOGICAL: Nivolumab, DRUG: Paclitaxel, OTHER: Questionnaire Administration, BIOLOGICAL: Ramucirumab
Advanced Esophageal Adenocarcinoma, Advanced Gastric Adenocarcinoma, Advanced Gastroesophageal Junction Adenocarcinoma, Clinical Stage II Esophageal Adenocarcinoma AJCC v8, Clinical Stage III Esophageal Adenocarcinoma AJCC v8, Clinical Stage III Gastric Cancer AJCC v8, Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8, Clinical Stage IV Esophageal Adenocarcinoma AJCC v8, Clinical Stage IV Gastric Cancer AJCC v8, Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8, Metastatic Esophageal Adenocarcinoma, Metastatic Gastric Adenocarcinoma, Metastatic Gastroesophageal Junction Adenocarcinoma, Unresectable Esophageal Adenocarcinoma, Unresectable Gastric Adenocarcinoma, Unresectable Gastroesophageal Junction Adenocarcinoma
Streamlined Treatment of Pulmonary Exacerbations in Pediatrics (STOP PEDS RCT)
Erika Enright - eenright@uw.edu
NCT06654752
Inclusion Criteria:
• Age
• For main cohort and non-HEMT cohort: age 6 to \<19 years
• For preschool cohort: age 3 to \<6 years
• Documentation of a CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and one or more of the following criteria:
• sweat chloride ≥ 60 mEq/liter
• two disease-causing variants in the cystic fibrosis transmembrane conductive regulator (CFTR) gene
• Written informed consent (and assent when applicable) obtained from participant or participant's legal representative and ability of participant to comply with the requirements of the study
• Highly Effective Modulator Therapy
• For main cohort and preschool cohort: Taking HEMT for at least 3 months at enrollment
• For non-HEMT cohort: not eligible for HEMT based on CFTR genotype or eligible but not taking for at least 3 months and no plans to start HEMT in the next year, and also not taking tezacaftor-ivacaftor or lumacaftor-ivacaftor for at least 3 months
• For main cohort and non-HEMT cohort: able to perform acceptable and reproducible spirometry
• For main cohort and non-HEMT cohort: ppFEV1 ≥ 50% predicted at enrollment based on the Global lung Initiative (GLI) reference equations
• Ability to receive text messages and access the internet
Exclusion Criteria:
• Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the individual or the quality of the data
• Receiving an acute course of oral or IV antibiotics at the time of enrollment or within the 14 days prior to enrollment. Individuals may be re-screened ≥21 days after completion of antibiotics if they are at their baseline state of health, per self-report
• Treatment with systemic corticosteroids at enrollment or within the 14 days prior to enrollment. Individuals may be re- screened ≥21 days after completion of systemic corticosteroids if they are at their clinical baseline, per self-report
• History of solid organ transplant
• History of positive culture for Mycobacterium abscessus in the 12 months prior to enrollment
• Treatment with antibiotics for any non-tuberculous mycobacteria (NTM) at enrollment
• Three or more IV antibiotic-treated PEx in the 12 months prior to enrollment
• Treatment with chronic oral antibiotics other than azithromycin at enrollment
• Treatment with systemic corticosteroids for allergic bronchopulmonary aspergillosis (ABPA) in the 12 months prior to enrollment
OTHER: Immediate Oral Antibiotics, OTHER: Tailored Treatment: Oral Antibiotics only if Additional Treatment needed
Cystic Fibrosis
cystic fibrosis, oral antibiotics, pulmonary exacerbation, pediatric
Parkinson's Foundation PD GENEration Genetic Registry
Kamalini Ghosh, MS - kghosh@parkinson.org
NCT04994015
Inclusion Criteria:
* Study Population 1: PWP (open for recruitment)
• Meet Movement Disorder Society (MDS) Clinical Diagnostic Criteria for Parkinson's Disease: probable diagnosis.
• Willingness to undergo genetic testing, and choose to be informed of genetic testing results for GBA, LRRK2 and 5 additional PD related genes (SNCA, VPS35, PRKN, PINK-1, PARK7).
• Capacity to give full informed consent in writing or electronically, and have read and signed the informed consent forms (ICFs) based on site clinician's determination.
• Able to perform study activities (including completion of either online, in-person or paper surveys). Study Population 2: People at risk of developing PD (not open for recruitment) 1\. Family members of Study Population 1 may be invited to participate in the study if confirmatory genetic testing is deemed necessary by the genetic testing laboratory.
Exclusion Criteria:
• Diagnosis of an atypical parkinsonian disorder (i.e., multiple system atrophy, progressive supranuclear palsy, dementia with Lewy bodies, corticobasal syndrome), including that due to medications, metabolic disorders, encephalitis, cerebrovascular disease, or normal pressure hydrocephalus.
• Individuals who have received a blood transfusion within the past 3 months.
• Individuals who have active hematologic malignancies such as lymphoma or leukemia.
• Individuals who have had a bone marrow transplant within the past 5 years.
• Under the age of 18
DEVICE: Lab Assay for seven genetic variants for Parkinson's Disease
Parkinson's Disease
Genetics, Genetic Counseling, Whole Genome Sequencing
A Study of Emapalumab for Pediatric Aplastic Anemia
Andromachi Scaradavou, MD - ScaradaA@mskcc.org
NCT06430788
Inclusion Criteria:
* Patients undergoing workup for suspected newly diagnosed sAA:
* Patients with severe cytopenias and a hypocellular marrow concerning for sAA
* Patients that meet the definition for suspected sAA (Camitta Criteria) as follows:
Marrow Cellularity: \<25%, or 25-50% with \<30% residual hematopoietic cells Peripheral cytopenias (at least 2 of 3) Absolute neutrophil count (ANC): \<500 x 10\^9/L Platelets: \<20 x 10\^9/L Absolute Reticulocyte Count: \<60 x 10\^9/L
* Patients that do not have evidence of leukemia or MDS
* Patients \< 25 years of age at time of diagnosis
* Able to tolerate emapalumab and IST (with standard institutional organ function criteria)
Exclusion Criteria:
* Uncontrolled infection at presentation.
* Patients who have undergone previous treatment for sAA.
* Patients with known inherited bone marrow failure
* Patient who has completed a full workup for sAA including having results back from telomere testing, DEB and genetics (when applicable), as well as having an appropriate willing and available donor and would otherwise be admitted for HSCT within 2 weeks of enrolling on the trial
* Patients with leukemia or MDS
* Patient or parent or guardian unable to give informed consent or unable to comply with the treatment protocol including research tests. BIOLOGICAL: Emapalumab
Aplastic Anemia, Cytopenia, Hypocellular Marrow
pediatric aplastic anemia, aplastic anemia, cytopenia, hypocellular marrow, Emapalumab, Memorial Sloan Kettering Cancer Center, 23-278
Study of Rondecabtagene Autoleucel in Aggressive Large B-Cell Lymphoma
Stephen Simko, MD - clinicaltrials@lyell.com
NCT05826535
Inclusion Criteria:
• Age 18 years or older
• Willing and able to provide written informed consent
• Histologically confirmed LBCL, including the following types defined by the World Health Organization (WHO 2022) or International Consensus Classification (2022)
• Received at least two prior lines of therapy for Cohorts 1, 2, and 4 and one prior line of therapy for Cohort 3
• Relapsed or refractory disease.
• At least 1 measurable lesion (per Lugano classification)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 or ECOG 0 to 2 (Cohort 5)
• Absolute neutrophil count (ANC) ≥ 1000/µL
• Platelet count ≥ 50,000/µL
• Absolute lymphocyte count (ALC) ≥ 200/µL Other protocol-defined criteria apply.
Exclusion Criteria:
• History of malignancy other than non-melanoma skin cancer or carcinoma in situ unless disease-free for at least 3 years
• Active central nervous system involvement
• History of cardiac lymphoma involvement or Epstein-Barr virus (EBV)+ lymphoma
• Ongoing or impending oncologic emergency
• Recent systemic anti-cancer therapy or radiation
• Ongoing non-hematologic toxicities due to prior therapy
• History of allogeneic stem cell or solid organ transplantation
• Autologous stem cell transplantation within 6 weeks
• History of prior genetically modified cell therapy (Cohorts 1, 3, 4, 5) or no other than a product targeting CD19 with an FMC63-based CAR (e.g., axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), or lisocabtagene maraleucel (liso-cel) (Cohort 2).
• Primary immunodeficiency
• History of autoimmune disease resulting in end organ injury or requiring recent therapy Other protocol-defined criteria apply.
DRUG: Rondecabtagene autoleucel (ronde-cel), DRUG: Fludarabine, DRUG: Cyclophosphamide
Relapsed Non-Hodgkin Lymphoma, Refractory Non-Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Large B-cell Lymphoma
CAR T-cell, Non-Hodgkin Lymphoma, CD19/20, CD19, CD20, NHL, Diffuse Large B-cell lymphoma, DLBCL, Transformed follicular lymphoma, TFL, Primary mediastinal B-cell lymphoma, PMBCL, Follicular lymphoma Grade 3B, Large cell follicular lymphoma, Aggressive B-cell NHL, Refractory Aggressive B-Cell Lymphoma, Refractory B-Cell Non-Hodgkin Lymphoma, Lymphoma, Non-Hodgkin, Lymphoma, Lymphoma, Large B-Cell, Diffuse, Cyclophosphamide, Fludarabine, Lymphoma, Follicular, Lymphoma, B-cell, Immunosuppressive Agents, Immunologic Factors, Disease Attributes, Immune System Diseases, Recurrence, PiNACLE
Comparing the Effectiveness of the Immunotherapy Agents Rituximab or Mosunetuzumab in Patients With Nodular Lymphocyte-Predominant Hodgkin Lymphoma, NORM Trial
ctrrecruit@vcu.edu
NCT05886036
Inclusion Criteria:
* Histopathologically confirmed diagnosis of NLPHL as confirmed by local pathologist's expert review.
* Untreated NLPHL: stage IB to IV according to Cotswolds. The proportion of patients with stages I or II treated with consolidative radiotherapy will be capped at 40%.
* Previously treated NLPHL, any stage.
* According to the treating physician, the patient should not be observed and needs therapy, notably because of B-symptoms (unexplained fever \[temperature \> 38 degrees Celsius (\> 100.4 degrees Fahrenheit)\], weight loss \[unexplained loss of \> 10 percent of body weight over the past six months\], or drenching night sweats), symptomatic nodal or extranodal disease, or patient preferences.
* Patients must have measurable disease according to the Lugano/Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) classification.
* Age \>= 18 years. Because no dosing or adverse event (AE) data are currently available on the use of mosunetuzumab in patients \< 18 years of age, children are excluded from this study.
* Eastern Cooperative Oncology Group performance status =\< 2 (Karnofsky \>= 60%).
* Absolute neutrophil count \>= 1,000/mcL.
* Platelets \>= 100,000/mcL.
* Total bilirubin =\< 1.5 institutional upper limit of normal (ULN), except in patients with Gilbert's syndrome as defined by \> 80% unconjugated bilirubin.
* Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine transaminase (ALT)(serum glutamic-pyruvic transaminase \[SGPT\]) =\< 3 x institutional ULN.
* Glomerular filtration rate (GFR) \>= 40mL /min= GFR (mL/Min/1.73 m\^2) \* body surface area (BSA)/1.73.
* Human immunodeficiency virus-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
* The effects of mosunetuzumab on the developing human fetus are unknown. For this reason and because other therapeutic agents used in this trial are known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal and/or barrier method of birth control; abstinence) (both hormonal and barrier method of birth control are required for participants in Canada) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men and women treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after completion of mosunetuzumab administration and 12 months after completion of rituximab administration.
* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.
Exclusion Criteria:
* Classical Hodgkin lymphoma (cHL) or composite lymphoma.
* Active transformed NLPHL, concerns of the treating physician of an active occult transformation or concerns of the treating physician that the patient needs cytotoxic therapy. Participants with a history of transformed NLPHL in complete remission for at least 2 years since completion of cytotoxic therapy are eligible
* NLPHL relapse less than 6 months after rituximab or rituximab-containing therapy.
* Patients who have not recovered from AEs due to prior anticancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia.
* Patients who are receiving any other investigational agents.
* Patients with central nervous system (CNS) involvement as a result of lymphoma.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to mosunetuzumab or rituximab.
* Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous.
* Pregnant women are excluded from this study because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with mosunetuzumab; breastfeeding should be discontinued if the mother is treated with mosunetuzumab or rituximab. These potential risks may also apply to other agents used in this study.
* Prior allogeneic stem cell or solid organ transplantation.
* Participants who have received a live, attenuated vaccine within 4 weeks before first dose of study treatment or anticipation that such a live, attenuated vaccine will be required during the study. Participants must not receive live, attenuated vaccines (e.g., FluMist \[registered trademark\]) while receiving study treatment and after the last dose until B-cell recovery to the normal ranges. Killed vaccines or toxoids should be given at least 4 weeks prior to the first dose of study treatment to allow development of sufficient immunity.
* Any other anti-cancer therapy, whether investigational or approved, including but not limited to chemotherapy, within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to initiation of study treatment.
* Evidence of any significant, concomitant disease that could affect compliance with the protocol or interpretation of results as judged by the investigator, including, but not limited to:
* Significant cardiovascular disease (e.g., New York Heart Association class III or IV cardiac disease, myocardial infarction within the previous 6 months, unstable arrhythmia, or unstable angina).
* Significant pulmonary disease (such as obstructive pulmonary disease or history of bronchospasm).
* Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease.
* Participants with a history of stroke who have not experienced a stroke or transient ischemic attack in the past 1 year and have no residual neurologic deficits as judged by the investigator are allowed.
* Participants with a history of epilepsy who have had no seizures in the past 2 years with or without anti-epileptic medications can be eligible only for the expansion cohort.
* History of confirmed progressive multifocal leukoencephalopathy (PML).
* Participants with infections requiring IV treatment with antibiotics or hospitalization (grade 3 or 4) within the last 4 weeks prior to enrollment or known active bacterial, viral (including SARS-CoV-2), fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment.
* Systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 2 weeks prior to first dose of study treatment.
* Known or suspected chronic active Epstein-Barr virus (EBV) or cytomegalovirus (CMV) infection.
* Known or suspected history of hemophagocytic lymphohistiocytosis (HLH). PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Biopsy, PROCEDURE: Computed Tomography, OTHER: Fludeoxyglucose F-18, BIOLOGICAL: Mosunetuzumab, PROCEDURE: Positron Emission Tomography, BIOLOGICAL: Rituximab, BIOLOGICAL: Rituximab and Hyaluronidase Human
Nodular Lymphocyte Predominant B-Cell Lymphoma, Recurrent Nodular Lymphocyte Predominant B-Cell Lymphoma, Refractory Nodular Lymphocyte Predominant B-Cell Lymphoma
Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) and Compensated Cirrhosis (AFFIRM)
Gilead Clinical Study Information Center - GileadClinicalTrials@gilead.com
NCT06051617
Inclusion Criteria:
Individuals must meet the following criteria to be eligible for study participation:
• Must be at least 18 years old.
• Must have a confirmed prior diagnosis of primary biliary cholangitis (PBC)
• Evidence of cirrhosis
• CP Score A or B
• Females of reproductive potential must use at least 1 barrier contraceptive and a second effective birth control method during the study and for at least 90 days after the last dose. Male individuals who are sexually active with female partners of reproductive potential must use barrier contraception, and their female partners must use a second effective birth control method during the study and for at least 90 days after the last dose
• Individuals must be able to comply with the instructions for study drug administration and be able to complete the study schedule of assessments (SOA)
Exclusion Criteria:
Individuals must not meet any of the following criteria to be eligible for study participation:
• Prior exposure to seladelpar
• A medical condition other than PBC that, in the Investigator's opinion, would preclude full participation in the study
• History of liver transplantation or actively listed for cadaveric or planned living donor transplant.
• Decompensated cirrhosis
• Evidence of portal vein thrombosis based on imaging at time of Screening by Doppler ultrasound or prior evidence by CT or MRI
• Hospitalization for liver-related complication within 12 weeks of Screening
• Laboratory parameters at Screening:
• Alkaline phosphatase (ALP) \< 1.5× Upper limit of normal (ULN) or ≥ 10×ULN
• Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) ≥5×ULN
• Total bilirubin (TB) ≤ 0.6 × ULN or ≥ 5 × ULN
• Platelet count ≤50×10\^3/µL
• Albumin ≤2.8 g/dL
• Estimated glomerular filtration rate (eGFR) \<45 mL/min/1.73 m\^2
• MELD score \>12. For individuals on anticoagulation medication, baseline International normalized ratio (INR) determination for MELD score calculation should take anticoagulant use into account, in consultation with the Medical Monitor.
• Serum alpha-fetoprotein (AFP) \>20 ng/mL
• INR \>1.7
• CP-C cirrhosis
• History or presence of other concomitant liver diseases
DRUG: Seladelpar, DRUG: Placebo
Primary Biliary Cholangitis
Primary Biliary Cholangitis (PBC), PBC
A Study to Evaluate Preventive Treatments for GPRC5D-related Oral Events (Talisman)
Study Contact - Participate-In-This-Study1@its.jnj.com
NCT06500884
Inclusion Criteria:
* Multiple myeloma (MM) according to IMWG diagnostic criteria
* Were triple-class exposed (received prior treatment with a PI, an IMiD, and anti CD38 mAb)
* Documented evidence of progressive disease based on investigator's determination of response by IMWG criteria on or after their last regimen
* Have an Eastern Cooperative Oncology Group-performance status (ECOG-PS) of 0 or 1 at screening. Participants with ECOG-PS 2 or 3 are eligible for the study if the ECOG-PS score is related to stable physical limitations (e.g., wheelchair-bound due to prior spinal cord injury) and not related to multiple myeloma or associated therapy
* Be willing and able to adhere to the lifestyle restrictions specified in the protocol
Exclusion Criteria:
* Contraindications or life-threatening known allergies, hypersensitivity, or intolerance to any study drug or its excipients
* Stroke, transient ischemic attack, or seizure within 6 months prior to screening
* Any of the following within 6 months prior to the first dose of study treatment: severe or unstable angina, myocardial infarction; major thromboembolytic event (e.g., pulmonary embolism, cerebrovascular accident), clinically significant ventricular arrythmia or heart failure New York Heart Association functional classification Class III or IV. Uncomplicated deep vein thrombosis is not considered exclusionary
* Major surgery or had significant traumatic injury within 2 weeks prior to the start of administration of study treatment, or will not have fully recovered from surgery, or has major surgery planned during the time the participant is expected to be treated in the study or within 2 weeks after administration of the last dose of study treatment
* A WETT score indicating severe dysgeusia at screening and confirmed prior to randomization. Also unresolved/severe dysgeusia referred by the participant or a finding in the physical examination/oral cavity inspection. Some examples include leukoplakia, prior mouth cancers, extensive dental caries, severe periodontitis, active oral infections, candidiasis, parotic gland removal, or radiotherapy with resultant xerostomia DRUG: Talquetamab, DRUG: Prophylaxis A, DRUG: Prophylaxis B, DRUG: Prophylaxis C, DRUG: Prophylaxis D, DRUG: Ramantamig
Multiple Myeloma
Liver Cirrhosis Network Rosuvastatin Efficacy and Safety for Cirrhosis in the United States (LCN RESCU)
Crystal Santillanes, MS - lcn@northwestern.edu
NCT05832229
Inclusion Criteria
• Age 18-75 years
• Cirrhosis due to NAFLD, ALD, or chronic viral hepatitis (treated HBV or HCV)
• Clinical diagnosis of cirrhosis as defined by investigator confirmation and the following: a. At least one liver biopsy within 5 years prior to consent showing either: Metavir stage 4 fibrosis; Ishak Stage 5-6 fibrosis, OR b. At least 2 of the following: i. Evidence on imaging: Nodular liver with either splenomegaly or recanalized umbilical vein within the past 48 weeks ii. Liver stiffness: VCTE within 48 weeks prior to consent or during Screening ≥15.0 kPa or MRE within 48 weeks prior to consent or during Screening ≥5 kPa iii. Evidence of varices demonstrated on imaging or endoscopy within 3 years prior to consent or during Screening iv. Either: FIB-4\>2.67 or platelets \<150/mL within 6 months prior to consent or during Screening
• Two measures of VCTE: one at screening and one at the open-label dispense study visit, meeting the following criteria:
• The first measure must be ≥ 15.0 kPa.
• The two measures must be at least 2 hours apart and no more than 60 days apart from one another.
• The mean of two measurements must be ≥ 15.0 kPa.
• Additionally, both screening and open-label dispense liver stiffness measures must be ≤50 kPa
• Compensated defined by:
• Absence of ascites/hydrothorax, hepatic encephalopathy or variceal bleeding currently or in the last 48 weeks, as determined clinically by investigator.
• If prior history of decompensation, must be without current symptoms of decompensation and no longer requiring treatment of complications for the last 48 weeks, including the use of diuretics for the treatment of ascites, and/or rifaximin or lactulose for the treatment of hepatic encephalopathy. Use of non-selective beta blockers will be allowed.
• Child-Pugh score \<8
• Provision of written informed consent. Exclusion Criteria
• Currently on a statin or any statin exposure within 24 weeks prior to consent.
• Known indication for statin therapy, defined as:
• Prior peripheral vascular, cardiovascular or cerebrovascular event for which statins are indicated for secondary prevention, OR
• Documented familial hypercholesterolemia, heterozygous familial hypercholesterolemia, OR
• Fasting LDL-C ≥ 190 mg/dL
• Myocardial infarction, Unstable angina, transient ischemic events, or stroke within 24 weeks of screening.
• Alcohol Use Disorder Identification Test (AUDIT) total score of ≥8 at screening.
• Patients with limitations in attending study visits.
• Prisoners.
• Known prior or current hepatocellular carcinoma (HCC) or cholangiocarcinoma.
• Known transjugular intrahepatic portosystemic shunt (TIPS), balloon retrograde transvenous obliteration (BRTO) or porto-systemic shunt surgery regardless of time of occurrence.
• Current (in past 24 weeks prior to consenting) use of medications known to cause hepatic fibrogenesis or confound endpoint assessment, defined as:
• amiodarone
• methotrexate
• warfarin
• Current (in past 24 weeks prior to consenting) use of medications which may increase risk for rosuvastatin-related myositis or DILI, defined as:
• fenofibrate
• erythromycin
• gemfibrozil
• niacin (500 mg or more)
• HIV protease inhibitors (darunivar, indinavir, nelfinavir, amprenavir)
• colchicine
• cyclosporin
• Additional medications that will be excluded: atazanavir/ritonavir capmatinib darolutamide dasabuvir/ombitasvir/paritaprevir/ritonavir ledipasvir/sofosbuvir elbasvir/grazoprevir erythromycin lopinavir/ritonavir regorafenib ritonavir, in any combination simeprevir sofbuvir/velpatasvir/voxilaprevir sofosbuvir/velpatasvir tafamidis tamoxifen teriflunomide \*If exposure was for 7 or less days for one of these medications can consider enrollment after 28 days from final dose.
• Presence of portal or hepatic vein thrombosis
• Diagnosis of untreated hypothyroidism or on unstable treatment regimen for hypothyroidism
• Receiving an elemental diet or parenteral nutrition
• Chronic pancreatitis or pancreatic insufficiency
• Etiology of cirrhosis other than ALD, NAFLD, or viral hepatitis (excluded diagnoses include cryptogenic immune-mediated such as AIH, PSC and PBC, cardiac cirrhosis or Fontan-associated liver disease, A1AT, Wilson's disease, etc.)
• Conditions which may confound study outcome: a. Unstable or active inflammatory bowel disease b. Active infection c. Any malignant disease (other than squamous or basal cell carcinoma of the skin) within previous 3 years d. Prior solid organ or hematopoietic cell transplant e. Bariatric surgery in the last 24 weeks prior to consent or planned bariatric surgery within the next 96 weeks f. Current liver-unrelated end-stage organ failures such as end-stage renal disease on dialysis, stage 3-4 congestive heart failure (CHF), current chronic obstructive pulmonary disease (COPD) on home oxygen.
• Known current medical or psychiatric conditions which, in the opinion of the investigator, would make the participant unsuitable for the study for safety reasons or interfere with or prevent adherence to the protocol.
• The following laboratory abnormalities within 90 days of screening: a. Hemoglobin \<10 g/dL b. Albumin \<3.0 g/dL c. Prolonged international normalized ratio (INR) \>1.5 d. Total bilirubin ≥ 2.0 mg/dl (unless due to Gilbert's syndrome or hemolysis as denoted by normal direct bilirubin fraction) e. Direct bilirubin ≥ 0.9 f. Uncontrolled diabetes (HbA1c ≥ 9.5%) within past 90 days.
• Kidney function abnormalities including:
• Dialysis
• Baseline eGFR \< 30 cc/min with CKD-Epi equation
• Known nephrotic proteinuria, defined as 3g or greater of protein in 24-hour urine collection
• Recent (within 48 weeks) or present hepatic decompensation with ascites/hydrothorax, hepatic encephalopathy or variceal bleeding
• Untreated chronic hepatitis B or C infection
• HCV eligible for enrollment if HCV RNA negative at baseline or documentation of prior SVR12
• HBV eligible if an HBV DNA \<100 IU/mL within the last 48 weeks and on treatment
• Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 200 U/L within the past 24 weeks or alkaline phosphatase (ALP) ≥ 300.
• Documented history of intolerance to statins
• Serious comorbid medical disease which in the investigator's opinion renders a life-expectancy less than 96 weeks
• Active illicit substance use (other than THC), including inhaled or injected drugs, in the 24 weeks prior to screening
• Pregnancy, planned pregnancy or breastfeeding
• Current participation in active medication treatment trials (within 24 weeks prior to randomization) or planned participation in active medication treatment trials simultaneous to participation in present trial.
• Significant existing muscle pain or tenderness or prior history of myasthenia gravis as determined by a site physician.
• Failure or inability to provide informed consent.
• East Asian Descent within one degree of relatedness (e.g., if the participant's parents are of East Asian descent)
• Age 18-75 years
• Cirrhosis due to NAFLD, ALD, or chronic viral hepatitis (treated HBV or HCV)
• Clinical diagnosis of cirrhosis as defined by investigator confirmation and the following: a. At least one liver biopsy within 5 years prior to consent showing either: Metavir stage 4 fibrosis; Ishak Stage 5-6 fibrosis, OR b. At least 2 of the following: i. Evidence on imaging: Nodular liver with either splenomegaly or recanalized umbilical vein within the past 48 weeks ii. Liver stiffness: VCTE within 48 weeks prior to consent or during Screening ≥15.0 kPa or MRE within 48 weeks prior to consent or during Screening ≥5 kPa iii. Evidence of varices demonstrated on imaging or endoscopy within 3 years prior to consent or during Screening iv. Either: FIB-4\>2.67 or platelets \<150/mL within 6 months prior to consent or during Screening
• Two measures of VCTE: one at screening and one at the open-label dispense study visit, meeting the following criteria:
• The first measure must be ≥ 15.0 kPa.
• The two measures must be at least 2 hours apart and no more than 60 days apart from one another.
• The mean of two measurements must be ≥ 15.0 kPa.
• Additionally, both screening and open-label dispense liver stiffness measures must be ≤50 kPa
• Compensated defined by:
• Absence of ascites/hydrothorax, hepatic encephalopathy or variceal bleeding currently or in the last 48 weeks, as determined clinically by investigator.
• If prior history of decompensation, must be without current symptoms of decompensation and no longer requiring treatment of complications for the last 48 weeks, including the use of diuretics for the treatment of ascites, and/or rifaximin or lactulose for the treatment of hepatic encephalopathy. Use of non-selective beta blockers will be allowed.
• Child-Pugh score \<8
• Provision of written informed consent. Exclusion Criteria
• Currently on a statin or any statin exposure within 24 weeks prior to consent.
• Known indication for statin therapy, defined as:
• Prior peripheral vascular, cardiovascular or cerebrovascular event for which statins are indicated for secondary prevention, OR
• Documented familial hypercholesterolemia, heterozygous familial hypercholesterolemia, OR
• Fasting LDL-C ≥ 190 mg/dL
• Myocardial infarction, Unstable angina, transient ischemic events, or stroke within 24 weeks of screening.
• Alcohol Use Disorder Identification Test (AUDIT) total score of ≥8 at screening.
• Patients with limitations in attending study visits.
• Prisoners.
• Known prior or current hepatocellular carcinoma (HCC) or cholangiocarcinoma.
• Known transjugular intrahepatic portosystemic shunt (TIPS), balloon retrograde transvenous obliteration (BRTO) or porto-systemic shunt surgery regardless of time of occurrence.
• Current (in past 24 weeks prior to consenting) use of medications known to cause hepatic fibrogenesis or confound endpoint assessment, defined as:
• amiodarone
• methotrexate
• warfarin
• Current (in past 24 weeks prior to consenting) use of medications which may increase risk for rosuvastatin-related myositis or DILI, defined as:
• fenofibrate
• erythromycin
• gemfibrozil
• niacin (500 mg or more)
• HIV protease inhibitors (darunivar, indinavir, nelfinavir, amprenavir)
• colchicine
• cyclosporin
• Additional medications that will be excluded: atazanavir/ritonavir capmatinib darolutamide dasabuvir/ombitasvir/paritaprevir/ritonavir ledipasvir/sofosbuvir elbasvir/grazoprevir erythromycin lopinavir/ritonavir regorafenib ritonavir, in any combination simeprevir sofbuvir/velpatasvir/voxilaprevir sofosbuvir/velpatasvir tafamidis tamoxifen teriflunomide \*If exposure was for 7 or less days for one of these medications can consider enrollment after 28 days from final dose.
• Presence of portal or hepatic vein thrombosis
• Diagnosis of untreated hypothyroidism or on unstable treatment regimen for hypothyroidism
• Receiving an elemental diet or parenteral nutrition
• Chronic pancreatitis or pancreatic insufficiency
• Etiology of cirrhosis other than ALD, NAFLD, or viral hepatitis (excluded diagnoses include cryptogenic immune-mediated such as AIH, PSC and PBC, cardiac cirrhosis or Fontan-associated liver disease, A1AT, Wilson's disease, etc.)
• Conditions which may confound study outcome: a. Unstable or active inflammatory bowel disease b. Active infection c. Any malignant disease (other than squamous or basal cell carcinoma of the skin) within previous 3 years d. Prior solid organ or hematopoietic cell transplant e. Bariatric surgery in the last 24 weeks prior to consent or planned bariatric surgery within the next 96 weeks f. Current liver-unrelated end-stage organ failures such as end-stage renal disease on dialysis, stage 3-4 congestive heart failure (CHF), current chronic obstructive pulmonary disease (COPD) on home oxygen.
• Known current medical or psychiatric conditions which, in the opinion of the investigator, would make the participant unsuitable for the study for safety reasons or interfere with or prevent adherence to the protocol.
• The following laboratory abnormalities within 90 days of screening: a. Hemoglobin \<10 g/dL b. Albumin \<3.0 g/dL c. Prolonged international normalized ratio (INR) \>1.5 d. Total bilirubin ≥ 2.0 mg/dl (unless due to Gilbert's syndrome or hemolysis as denoted by normal direct bilirubin fraction) e. Direct bilirubin ≥ 0.9 f. Uncontrolled diabetes (HbA1c ≥ 9.5%) within past 90 days.
• Kidney function abnormalities including:
• Dialysis
• Baseline eGFR \< 30 cc/min with CKD-Epi equation
• Known nephrotic proteinuria, defined as 3g or greater of protein in 24-hour urine collection
• Recent (within 48 weeks) or present hepatic decompensation with ascites/hydrothorax, hepatic encephalopathy or variceal bleeding
• Untreated chronic hepatitis B or C infection
• HCV eligible for enrollment if HCV RNA negative at baseline or documentation of prior SVR12
• HBV eligible if an HBV DNA \<100 IU/mL within the last 48 weeks and on treatment
• Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 200 U/L within the past 24 weeks or alkaline phosphatase (ALP) ≥ 300.
• Documented history of intolerance to statins
• Serious comorbid medical disease which in the investigator's opinion renders a life-expectancy less than 96 weeks
• Active illicit substance use (other than THC), including inhaled or injected drugs, in the 24 weeks prior to screening
• Pregnancy, planned pregnancy or breastfeeding
• Current participation in active medication treatment trials (within 24 weeks prior to randomization) or planned participation in active medication treatment trials simultaneous to participation in present trial.
• Significant existing muscle pain or tenderness or prior history of myasthenia gravis as determined by a site physician.
• Failure or inability to provide informed consent.
• East Asian Descent within one degree of relatedness (e.g., if the participant's parents are of East Asian descent)
DRUG: Rosuvastatin
Cirrhosis, Cirrhosis, Liver, Cirrhosis Early, Cirrhosis Due to Hepatitis B, Cirrhosis Advanced, Cirrhosis Infectious, Cirrhosis Alcoholic, Cirrhosis Due to Hepatitis C
Cirrhosis, Liver, Nonalcoholic Fatty Liver Disease
FearLess in NeuroOncology
Mary Bridgman - LiveNOW@vcu.edu
NCT06989086
Inclusion Criteria:
Patients:
* Self-report a diagnosis of a primary malignant brain tumor (grade II-IV)
* \>2 weeks post-cranial resection or biopsy
* Elevated Fear of Recurrence Distress Rating
* Primarily English speaking
* \>/= 18 years of age at the time of enrollment
Caregivers:
* nonprofessional caregiver to a patient with a primary malignant brain tumor (grade II-IV)
* Elevated Fear of Recurrence Distress Rating
* Primarily English speaking
* \>/= 18 years of age at the time of enrollment
Exclusion Criteria:
Patient / Caregiver Exclusion:
* Cognitive impairment that might prohibit active intervention engagement
* Inability to understand and provide informed consent
* Inability to attend virtual sessions due to unstable or no internet connection BEHAVIORAL: Fearless in Neuro-Oncology
Primary Malignant Brain Tumor, Glioblastoma (GBM), Astrocytoma, Oligodendroglioma, Caregiver
brain tumor
A Study of CREXONT (Carbidopa and Levodopa) Extended-Release Capsules in Participants With Parkinson's Disease
ctrrecruit@vcu.edu
NCT06765668
Inclusion Criteria:
• Participants with PD consistent with the United Kingdom Parkinson's Disease Society Brain Bank Diagnostic Criteria and who are being treated with stable regimens of oral CD-LD.
• Participants with a score of at least 20 units at Screening on the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III total score in the "Off" state.
• Participants with predictable "Off" periods at Screening defined by a score of 1 or 2 (Complexity of Motor Fluctuations) of the MDS-UPDRS Part IV B (Motor Fluctuations).
• By history, for the 4 weeks (28 days) prior to Screening, the participant experiences.
• Daily predictable "wearing-off" episodes with periods of worsening motor symptoms.
• An average of at least 2.5 cumulative hours per day of "Off" time, during the hours the participant awake.
• At Screening, the participant is able to differentiate "On" state from "Off" state as determined by at least 75 percentage (%) concordance with a trained rater (that is, investigator or qualified and certified site staff) in "On/Off" ratings for 8 ratings over a 4-hour training period. The concordance must include at least one "On" and one "Off" rating in this 4-hour training period.
• If the concordance is less than 75%, or if it does not include at least one "On" and one "Off" rating within the first 4-hour training period, a second 4-hour training period should be conducted with the participant before being considered for inclusion in the study.
• If during the second 4-hour training-period a concordance of at least 75% is also not achieved, or if it does not include at least one "On" and one "Off" rating, the participant cannot be included in the study.
• At baseline (Visit 1), review of the 3-day PD diaries confirms the following:
• The participant is able to properly complete the PD diaries with valid entries. Inability to properly complete the diaries is indicated when more than 1 day of a diary is not returned or if more than 1 day of the diary is not valid (that is, more than 2 hours \[4 half-hour periods\] of the 24-hour diary day are missing); and
• The participant has an average of at least 2.5 hours per day of "Off" time, during the hours the participant is awake, over the 3 PD diary days; and
• The participant has at least 1.5 hours of cumulative "Off" time, during the hours the participant is awake, on each of the 3 PD diary days.
• Participant is responsive to CD-LD therapy and currently being treated on a stable regimen of oral CD-LD for at least 4 weeks (greater than equal to \[\>=\] 28 days) prior to baseline (Visit 1) and meets the following criteria: a. Daily Dose Requirements: i. All participants should be taking at least 100 mg of immediate-release (IR) CD-LD or 195 mg of Rytary for the first morning dose. ii. For participants taking IR CD-LD (with or without a bedtime dose of CR CD-LD): * Require a total daily dose of at least 300 mg of LD and a maximum total daily dose of less than equal to \[\<=\]1200 mg LD (from IR CD-LD alone or from IR CD-LD in combination with a single daily bedtime dose of CR CD-LD). * The maximum individual dose allowed is 250 mg of LD. * The minimum individual dose should be at least 100 mg of LD. iii. For participants using a catechol-O-methyltransferase (COMT) inhibitor: * Require a total daily dose of at least 300 mg of LD and a maximum total daily dose of less than \[\<\]1000 mg LD. * The maximum individual dose is 200 mg of LD. iv. For participants using Rytary: * Require a total daily dose of at least 585 mg of LD and a maximum total daily dose of \<2100 mg LD. * The maximum individual dose is 685 mg of LD. b. Dose Frequency Requirement: i. If a participant is using IR/CR CD-LD alone or in combination with a COMT inhibitor, then the dosing frequency must be 3 to 6 times daily. ii. If a participant is using Rytary, then the dosing frequency must be 3 to 4 times daily.
• Participant is able and willing to provide written informed consent prior to the conduct of any study-specific procedures.
• Participant is able and willing to comply with the protocol, including completion of PD diaries, questionnaires, and available for all study visits and telephone calls.
• Participants who have participated in prior CREXONT clinical studies are allowed to be enrolled in this Phase 4 study.
Exclusion Criteria:
• Participant who, in the opinion of the clinical investigator, should not participate in the study based on the CREXONT Prescribing Information.
• Participant had a prior neurosurgical treatment for PD (example, deep brain stimulation \[DBS\] surgery or neurosurgical ablation treatment procedures) or if such procedure is planned or anticipated prior to Visit 4 (Day 42) of the study.
• Participant received the following within 4 weeks (\<=28 days) prior to baseline (Visit 1)
• Any doses of a CR CD-LD apart from a single daily bedtime dose.
• Duopa.
• Nonselective monoamine oxidase inhibitor (MAOI).
• Rescue medication used to treat "off" episodes for example: apomorphine or inhaled LD (Inbrija®).
• Received any investigational drugs within 30 days or 5 times the half-life, whichever is longer, prior to baseline (Visit 1).
• Participant who, in the opinion of the clinical investigator, should not participate in the study (example, based on clinical assessment, participant does not adequately comprehend the terminology needed to complete the PD diary and participant -reported outcomes, or any other reason).
• Employees or family members of the investigator, or study site staff, or Sponsor.
DRUG: CREXONT ER
Parkinson Disease
Study to Check the Safety of Fazirsiran and Learn if Fazirsiran Can Help People With Liver Disease and Scarring (Fibrosis) Due to an Abnormal Version of Alpha-1 Antitrypsin Protein
Takeda Contact - medinfoUS@takeda.com
NCT05677971
Inclusion criteria:
* The participant must have a diagnosis of the Z allele homozygotes (PiZZ) genotype AATD. PiZZ diagnosis from source verifiable medical records is permitted. Otherwise, participants must undergo PiZZ confirmatory testing (genotyping for PiS and PiZ alleles) at screening. PiMZ or PiSZ genotypes are not permitted.
* The participant, of any sex, is aged 18 to 75 years, inclusive.
* The participant's liver biopsy core sample collected should meet the requirements of the protocol.
* The participant has evidence of METAVIR stage F2, F3, or F4 liver fibrosis, evaluated by a centrally read baseline liver biopsy during the screening period; or confirmed as meeting all the entry criteria by central reading of a previous biopsy conducted within 6 months before the estimated enrollment date using an adequate liver biopsy and slides as defined in the study laboratory manual.
* The participant has a pulmonary status meeting the protocol's requirements.
* It must be confirmed that the participant does not have HCC. Participants will be screened for HCC with alpha-fetoprotein (AFP) and abdominal ultrasound. If the participant has any of the following, they will be required to have contrast-enhanced CT or MRI imaging to exclude HCC before randomization.
* An adult participant must have a body mass index (BMI) greater than or equal to (\>=) 18.0 kilograms per meter square (kg\^m2).
* The participant is a nonsmoker for at least 6 months before screening.
Exclusion Criteria
* The participant has a history of liver decompensating events (overt hepatic encephalopathy \[West Haven Grade \>=2\] documented by a physician or healthcare professional, clinically significant ascites, spontaneous bacterial peritonitis, GI bleeding from varices, hepatopulmonary syndrome, hepatorenal syndrome, portal pulmonary hypertension, or bleeding portal hypertensive gastropathy).
* The participant has a history of the presence of medium or large varices or varices with red wale signs based on a previous esophagogastroduodenoscopy (EGD) within 6 months before the estimated enrollment date. For certain participants, an EGD will be required at screening if there is no EGD available within 6 months before the estimated enrollment date. Presence of small varices with no red wale signs on EGD and no history of bleeding will be acceptable for study eligibility.
* The participant has evidence of chronic liver disease attributable to other diseases, including viral hepatitis B or C, primary biliary cholangitis, primary sclerosing cholangitis, Wilson disease, alcoholic hepatitis, hemochromatosis, liver cancer, history of biliary diversion, or autoimmune hepatitis.
* The participant has alanine transaminase (ALT) or aspartate transaminase (AST) levels \>250 units per liter (U/L).
* The participant has a platelet count \<60,000 per cubic millimeter (mm\^3) (\<60 × 10\^9 per liter \[10\^9/L\]).
* The participant has albumin \<=2.8 gram per deciliter (g/dL) (28 grams per liter \[g/L\]).
* The participant has international normalized ratio (INR) \>=1.7.
* The participant is expected to have severe and unavoidable high-level exposure to inhaled pulmonary toxins during the study such as may occur with occupational exposure to mineral dusts or metals.
* The participant has a history of drug abuse (such as cocaine, phencyclidine) within 1 year before the screening visit or has a positive urine drug screen at screening.
* The participant has previously been treated with fazirsiran or any other RNAi for AATD-LD.
* The participant has portal vein thrombosis.
* The participant has a prior transjugular portosystemic shunt procedure.
* The participant has a history of malignancy within the last 5 years, except for adequately treated basal cell carcinoma, squamous cell skin cancer, superficial bladder tumors, or in situ cervical cancer. Participants with other curatively treated malignancies who have no evidence of metastatic disease and a greater than 1-year disease-free interval may be entered after approval by the medical monitor.
DRUG: Fazirsiran Injection, OTHER: Placebo
Alpha1-Antitrypsin Deficiency
A Study of Treatment for Medulloblastoma Using Sodium Thiosulfate to Reduce Hearing Loss
ctrrecruit@vcu.edu
NCT05382338
Inclusion Criteria:
* PRE-ENROLLMENT: Patients must be ≥ 4 years and ≤ 21 years of age at the time of enrollment
* PRE-ENROLLMENT: Patient is suspected to have newly-diagnosed medulloblastoma by institutional diagnosis
* Please note: Patients with a pending result of CSF cytology tests are eligible for NCI-2014-02057 (APEC14B1-Central Nervous System \[CNS\]) and CNS/Medulloblastoma Pre Enrollment Eligibility Screening
* PRE-ENROLLMENT: The patient and/or their parents or legal guardians must have signed informed consent for APEC14B1 Part A - Eligibility Screening and consent for the Molecular Characterization Initiative (MCI)
* PRE-ENROLLMENT: The required specimens are projected to be submitted under APEC14B1-CNS as soon as possible, preferably within 5 days of definitive surgery
* PRE-ENROLLMENT: All patients must have rapid central pathology review under APEC14B1-CNS prior to study enrollment on ACNS2031 step 1 in order to avoid discordant diagnoses and to verify diagnosis criterion for treatment on ACNS2031.
* Note: Patients with a pending result of CSF cytology tests are eligible for the rapid central pathology screening review. Confirmation of CSF negativity is needed for enrollment on the ACNS2031 protocol
* PRE-ENROLLMENT: All patients must have rapid central molecular screening review under APEC14B1-CNS prior to study enrollment on ACNS2031 step 1, in order to avoid discordant diagnoses and to verify diagnosis criterion for treatment on ACNS2031
* PRE-ENROLLMENT: All patients who have histopathology confirmed must have rapid central imaging screening review under APEC14B1 prior to study enrollment on ACNS2031 step 1
* Note: Patients must not have metastatic disease on cranial or spinal MRI. Patients with \> 1.5 cm\^2 residual tumor after initial surgical resection may undergo a second surgical resection prior to subsequent therapy to render them eligible for this study. The day of the second resection to remove residual tumor will be regarded as the day of definitive surgery (Day 0) and must be within a month (31 days) of the initial resection
* PRE-ENROLLMENT: All patients who have histopathology confirmed must have rapid central audiology review under APEC14B1-CNS prior to study enrollment on ACNS2031 step 1
* Patients must be \>= 4 years and =\< 21 years of age at the time of enrollment
* Patients must be newly diagnosed and have eligibility confirmed by rapid central pathology and molecular screening reviews performed on APEC14B1 and via the Molecular Characterization Initiative
* Average-risk cohort
* Clinico-pathologic criteria:
* M0 disease
* No diffuse anaplastic histology AND
* Molecular criteria:
* SHH, p53wt, GLI2 normal, MYCN normal, no chromosome 14q loss
* Group 3, MYC normal, no isochromosome 17q
* Group 4, no chromosome 11 loss
* Low-risk features cohort
* Clinico-pathologic criteria:
* M0 disease
* No diffuse anaplastic histology AND
* Molecular criteria:
* Group 4, chromosome 11 loss
* Patients must have negative lumbar CSF cytology
* Note: CSF cytology for staging should be performed no sooner than 14 days post operatively to avoid false positive CSF. Ideally, CSF should be obtained between day 14 and day 21 to allow for final staging status before enrollment onto the study. Patients with positive CSF cytology obtained 0 to 14 days after surgery should have cytology repeated to determine eligibility and final CSF status. Patients with negative CSF cytology from lumbar puncture obtained 0 to 14 days after surgery do not need cytology repeated. Patients with negative CSF cytology from lumbar puncture obtained prior to surgery do not need cytology repeated post-operatively
* Patients must have eligibility confirmed by Rapid Central Imaging Review performed on APEC14B1. Patients must have =\< 1.5 cm\^2 cross-sectional area of residual tumor. Whole brain MRI with and without gadolinium and spine MRI with gadolinium must be performed
* Patients must weigh \> 10 kg
* Patients must be enrolled, and protocol therapy must be projected to begin, no later than 31 days after definitive diagnostic surgery (day 0)
* Peripheral absolute neutrophil count (ANC) \>= 1000/uL (within 7 days prior to enrollment)
* Platelet count \>= 100,000/uL (transfusion independent) (within 7 days prior to enrollment)
* Hemoglobin \>= 8.0 g/dL (may receive red blood cell count \[RBC\] transfusions) (within 7 days prior to enrollment)
* A serum creatinine (within 7 days prior to enrollment) based on age/sex as follows:
* 4 to \< 6 years (age); 0.8 mg/dL (male) 0.8 mg/dL (female)
* 6 to \< 10 years (age); 1 mg/dL (male) 1 mg/dL (female)
* 10 to \< 13 years (age); 1.2 mg/dL (male) 1.2 mg/dL (female)
* 13 to \< 16 years (age); 1.5 mg/dL (male) 1.4 mg/dL (female)
* \>= 16 years (age); 1.7 mg/dL (male) 1.4 mg/dL (female) OR a 24 hour urine Creatinine clearance \>= 70 mL/min/1.73 m\^2 (within 7 days prior to enrollment) OR a glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 (within 7 days prior to enrollment). GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
* Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
* Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L (within 7 days prior to enrollment)
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
* Central nervous system function defined as:
* Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
* Patients must not be in status epilepticus, a coma or assisted ventilation at the time of study enrollment
* Auditory function defined as:
* Patients must have normal hearing (defined as International Society of Pediatric Oncology \[SIOP\] grade 0) in at least one ear confirmed by rapid central audiology review performed on APEC14B1 prior to enrollment
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
* Patients with metastatic disease by either MRI evaluation or lumbar CSF cytology are not eligible. Patients who are unable to undergo a lumbar puncture for assessment of CSF cytology are ineligible
* Patients must not have received any prior radiation therapy or chemotherapy (tumor-directed therapy) other than surgical intervention and/or corticosteroids
* Patients must not have any known hypersensitivity to STS, sulfates/sulfites, or other thiol agents (e.g., amifostine, n-acetylcysteine, MESNA, and captopril)
* Pregnancy and Breastfeeding:
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation PROCEDURE: Audiometric Test, PROCEDURE: Auditory Brainstem Response, PROCEDURE: Biospecimen Collection, DRUG: Cisplatin, DRUG: Cyclophosphamide, DRUG: Lomustine, PROCEDURE: Magnetic Resonance Imaging, OTHER: Quality-of-Life Assessment, RADIATION: Radiation Therapy, DRUG: Sodium Thiosulfate, OTHER: Survey Administration, DRUG: Vincristine
Childhood Medulloblastoma
A Long-Term Study of Elafibranor in Adult Participants With Primary Biliary Cholangitis (ELFIDENCE)
Ipsen Clinical Study Enquiries - clinical.trials@ipsen.com
NCT06016842
Inclusion Criteria :
* Male or female participants must be ≥18 years of age at the time of signing the informed consent.
* Participants with a definite or probable diagnosis of primary biliary cholangitis (PBC)
* Participants with cirrhosis at SV1. • Participants must be Child Pugh A or Child Pugh B.
* Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
* Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Exclusion Criteria :
* History or presence of other concomitant liver disease including but not limited to:
* i) Primary sclerosing cholangitis (PSC).
* ii) Autoimmune hepatitis (AIH) by simplified Diagnostic Criteria of the International Autoimmune Hepatitis Group (IAIHG) ≥6, or if treated for an overlap of PBC with AIH, or if there is clinical suspicion and evidence of overlap AIH features, that cannot be explained alone by insufficient response to UDCA.
* iii) Positive hepatitis B surface antigen (HBsAg). Participants with negative HBsAg and positive hepatitis B core antibody (HBcAb) may be eligible if hepatitis B virus deoxyribonucleic acid (HBV DNA) is negative.
* iv) Hepatitis C virus (HCV) infection defined by positive anti-HCV antibody and positive HCV ribonucleic acid (RNA) (Note: Participants with positive anti-HCV antibody due to previously treated HCV infection, may be enrolled if a confirmatory HCV RNA is undetectable and sustained viral response has been documented).
* v) Alcohol-associated liver disease (ALD).
* vi) Nonalcoholic steatohepatitis (NASH).
* vii) Other chronic liver diseases, such as alpha-1 antitrypsin deficiency.
* History or presence of clinically significant hepatic decompensation, including:
* i) History of liver transplantation, current placement on a liver transplant list, current model for end-stage liver disease including (MELD) 3.0 score \>12 due to hepatic impairment.
* ii) Evidence of complications of cirrhosis, including hepatic decompensation or evidence of significant portal hypertension complications including presence of uncontrolled ascites; history of variceal bleeding or related interventions (e.g. variceal banding, or transjugular intrahepatic portosystemic shunt placement); presence of hepatic encephalopathy Grade 2 or higher per West-Haven criteria; history or presence of spontaneous bacterial peritonitis. Note: participants with low-risk varices (Grade I) without history of bleeding or other treatment may be eligible to enrol.
* iii) Hepatorenal syndrome (HRS) (type I or II ). • vi) Hospitalisation for liver-related complication within 12 weeks prior to SV1.
* Known history of human immunodeficiency virus (HIV) infection or having a positive confirmatory test for HIV type 1 or 2.
* Medical conditions that may cause non-hepatic increases in ALP (e.g. Paget's disease).
* Evidence of any other unstable or untreated clinically significant immunological, endocrine, hematologic, gastrointestinal, neurological, or psychiatric disease as evaluated by the investigator; other clinically significant conditions that are not well controlled.
* Non-hepatic medical conditions that may diminish life expectancy to \<2 years, including known cancers.
* History of hepatocellular carcinoma.
* Alpha-fetoprotein (AFP) \>20 ng/mL with 4-phase liver computerised tomography (CT) or magnetic resonance imaging (MRI) imaging suggesting presence of hepatocellular carcinoma.
* Known malignancy or history of malignancy within the last 5 years. Participants with non-melanoma skin cancer, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
* Administration of the following medications is prohibited during the study, and prior to the study as per the timelines specified below: • i) 3 months prior to baseline: fibrates, seladelpar, glitazones, obeticholic acid, azathioprine, cyclosporine, methotrexate, mycophenolate, pentoxifylline, budesonide and other systemic corticosteroids (parenteral and oral chronic administration only); potentially hepatotoxic drugs (including α-methyl-dopa, sodium valproic acid, isoniazid or nitrofurantoin).
* Participants who are currently participating in, plan to participate in, or have participated in an investigational drug study or medical device study containing active substance within 30 days or 5 half-lives, whichever is longer, prior to the screening period.
i) If the previous study was for an experimental therapy being studied for potential benefit in PBC, and the potential therapeutic agent was proven to have no beneficial effect in PBC and there are no safety concerns, the participant may enrol after 30 days or 5 half-lives from the last dose of the therapeutic agent, whichever is longer.ii) For therapeutic agents being studied for potential benefit in PBC for which it is still unclear if there may be a potential benefit, participants may enrol after 6 months from the last dose of the therapeutic agent.
* Electrocardiogram (ECG) with QT interval corrected by Fridericia's formula (QTcF) \>450 msec in males or QTcF \>470 msec in females for participants without bundle branch block. For participants with bundle branch block or other intraventricular conduction delay, a longer QTcF \>480 msec would be exclusionary.
* Total bilirubin (TB) \>5x ULN
* Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \>5x ULN at SV1
* Creatinine phosphokinase (CPK) \>2x ULN.
* Platelet count \<50,000/μL
* International normalised ratio (INR) \>1.8 in the absence of anticoagulant therapy.
* Estimated glomerular filtration rate (eGFR) \<45 mL/min/1.73m2 per the Modification of Diet in Renal Disease (MDRD)-6 Study formula at SV1.
* Significant renal disease, including nephritic syndrome, chronic kidney disease (CKD) (defined as participants with evidence of significantly impaired kidney function or underlying kidney injury).
* For female participants: known current pregnancy, or has a positive serum pregnancy test, or is breastfeeding.
* Participants unwilling or unable to be abstinent from alcohol during the study.
* History of alcohol abuse, or other substance abuse within 1 year prior to SV1.
* Known hypersensitivity to elafibranor or to any of the excipients of the investigational product(s).
* Mental instability or incompetence, such that the validity of informed consent or ability to be compliant with the study is uncertain.
* Any other condition that, in the opinion of the investigator, would interfere with study participation or completion, or would put the participant at risk, including a potential participant assessed as being at high risk of noncompliance with the study.
* Alkaline phosphatase (ALP) ≥10x ULN.
* Albumin \<2.8 g/dL due to impaired hepatic function.
DRUG: Elafibranor, OTHER: Matched 80 mg placebo
Primary Biliary Cholangitis (PBC)
Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
ctrrecruit@vcu.edu
NCT05432804
Inclusion Criteria:
* Patients must have histologically confirmed glioblastoma (IDH wild-type, MGMT promoter methylated) that has undergone resection or biopsy upon first recurrence. Recurrence at site of prior involvement is defined by histopathological evidence of viable neoplastic cells associated with any of the following: mitotic activity, increased proliferation rate, micro-endothelial proliferation, or pseudo-palisading necrosis
* Prior to resection or biopsy, patients must have measurable disease, defined as at least one bi-dimensional contrast-enhancing lesion with clearly defined margins, with 2 perpendicular diameters of at least 10 mm, visible on \>= 2 axial slices
* Patients must have received first-line treatment of temozolomide plus radiotherapy
* Patients must not have received any prior therapy aside from resection or biopsy for their recurrent disease
* Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of selinexor (KPT-330) in combination with temozolomide in patients \< 18 years of age, children are excluded from this study
* Karnofsky performance status \>= 60% (Eastern Cooperative Oncology Group \[ECOG\] =\< 2)
* Absolute neutrophil count \>= 1,500/mcL
* Platelets \>= 100,000/mcL
* Hemoglobin \>= 10 g/dL
* Total bilirubin =\< 2 x institutional upper limit of normal (ULN)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine transaminase (ALT) (serum glutamic-pyruvic transaminase \[SGPT\]) =\< 3 x institutional ULN
* Glomerular filtration rate (GFR) \>= 30 mL/min/1.73 m\^2
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
* The effects of selinexor (KPT-330) and temozolomide on the developing human fetus are unknown. For this reason and because selective nuclear export inhibitors as well as deoxyribonucleic acid (DNA) alkylating agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, and for 180 days after the last dose of temozolomide. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 90 days after completion of study treatment administration
* Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity who have a legally-authorized representative (LAR) and/or family member available will also be eligible
Exclusion Criteria:
* Patients who have had chemotherapy must have full recovery of organ and marrow function following the nadir of the last chemotherapy cycle
* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia
* Patients who are receiving any other investigational agents
* Patients who have previously received bevacizumab
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to selinexor (KPT-330) or temozolomide
* History of hypersensitivity to dacarbazine (DTIC), since both dacarbazine and temozolomide are metabolized to 5-(3-methyltriazen-1-yl)-imidazole-4-carboxamide (MTIC)
* Patients with uncontrolled intercurrent illness
* Pregnant women are excluded from this study because selinexor (KPT-330) is a selective inhibitor of nuclear export with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with selinexor (KPT-330), breastfeeding is not allowed for mothers during treatment with selinexor (KPT-330) and for 7 days after the last dose. These potential risks may also apply to other agents used in this study
* Hospitalized patients with severe coronavirus disease of 2019 (COVID-19) who are \>= 75 years old, or with a high-risk COVID-GRAM score, or with lactate dehydrogenase (LDH) \> 370 (U/L) AND D-Dimer \> 600 mcg/L FEU should not receive low-dose selinexor (KPT-330) pending additional results PROCEDURE: Biospecimen Collection, PROCEDURE: Magnetic Resonance Imaging, DRUG: Placebo Administration, DRUG: Selinexor, DRUG: Temozolomide
Recurrent Glioblastoma, IDH-Wildtype, Recurrent MGMT-Methylated Glioblastoma
A Study to Evaluate Vimseltinib in Adults With Active Chronic Graft-Versus-Host Disease (cGVHD)
Clinical Team - clinicaltrials@deciphera.com
NCT06619561
Inclusion Criteria:
• Must be allogeneic hematopoietic stem cell transplant (HSCT) recipients with moderate to severe cGVHD requiring systemic immune suppression. a. May have persistent active acute GVHD (aGVHD) and chronic GVHD (cGVHD) manifestations (overlap syndrome).
• Participants with active cGVHD who have received and failed at least 2 prior lines of systemic therapy.
• Stable dose of systemic corticosteroids is permitted but not required. If being taken, participants should be on a stable dose of corticosteroids for at least 2 weeks prior to starting study drug treatment.
• Adequate organ and bone marrow functions.
• Participants of reproductive potential agree to follow the contraception requirements.
• Karnofsky Performance Scale (KPS) of ≥60.
Exclusion Criteria:
• Has aGVHD without manifestations of cGVHD.
• Prior use of colony-stimulating factor 1 receptor (CSF1R) inhibitor for cGVHD.
• History or other evidence of severe illness, uncontrolled infection, or any other conditions that would make the participant unsuitable for the study. All wounds must be healed and free of infection or dehiscence.
• History of malignancy except for:
• Underlying malignancy for which the transplant was performed
• Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years prior to enrollment and felt to be at low risk for recurrence.
• Malabsorption syndrome or other illness that could affect oral absorption.
DRUG: Vimseltinib
Chronic Graft-Versus-Host Disease (cGVHD)
Allogeneic hematopoietic stem cell transplant (HSCT), Graft-Versus-Host Disease, GVHD, cGVHD, Graft versus host disease, Immune System Diseases, Organizing Pneumonia, Bronchiolitis Obliterans, Bronchiolitis, Bronchial Diseases, Respiratory Tract Diseases, Lung Diseases, Obstructive, Lung Diseases, Bronchiolitis Obliterans Syndrome, Graft vs Host Disease, Sclerosis, Fibrosis, Hematopoietic stem cell transplantation, Liver diseases
Zanubrutinib in Patients With DLBCL and MYD88 or NOTCH1 Mutation or CD5+
Massey IIT Research Operations - masseyepd@vcu.edu
NCT06846463
Inclusion Criteria:
* Patients must have a documented pathologic diagnosis of DLBCL at any stage.
* Must have documented MYD88 L265P, CD79B, or NOTCH1 truncation mutation or be CD5+ by IHC.
* Age ≥18 years on the day of signing the informed consent form.
* Patients must have measurable disease on Positron Emission Tomography-Computed Tomography scan (CT/PET) imaging.
* Patient must have received no more than one cycle of R-CHOP prior to enrollment. Length of time between first R-CHOP treatment and planned 2nd R-CHOP treatment should vary by no more than 21 days ± 3 days.
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.
* Adequate bone marrow function as defined by:
* Absolute neutrophil count (ANC) ≥1000/mm3, except for patients with bone marrow involvement in which ANC must be ≥500/mm3.
* Platelet ≥75,000/mm3, except for patients with bone marrow involvement in which the platelet count must be ≥30,000/mm3.
* Hemoglobin ≥7 g/dL, after transfusion if necessary
* Adequate organ function defined as:
* Creatinine clearance ≥30 mL/min as estimated by the Cockcroft-Gault equation.
* Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase, and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase ≤2.5 × upper limit of normal (ULN).
* Serum total bilirubin ≤3 x ULN (except patients with Gilberts syndrome 3g/dl).
* Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment.
* Women of childbearing potential and men must agree to use one of the following highly effective forms of birth control during the treatment and for 1 month following completion of study treatment for women and for 1 week following completion of study treatment for men.
* combined (estrogen and progestogen containing) hormonal contraception:
* oral
* intravaginal
* transdermal
* progestogen-only hormonal contraception associated with inhibition of ovulation
* oral
* injectable
* implantable
* intrauterine device (IUD)
* intrauterine hormone-releasing system (IUS)
* bilateral tubal occlusion
* vasectomized partner
* heterosexual abstinence
* Patients must not have any known allergies, hypersensitivity or intolerance to corticosteroids or monoclonal antibodies.
* Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments.
Exclusion Criteria:
* Patients with high grade B-cell lymphoma with myelocytomatosis oncogene /immunoglobulin heavy-chain (MYC)/IGH and BCL-2 rearrangements.
* Patients with brain metastasis.
* Patients with peripheral neuropathy CTCAE grade ≥2.
* Any uncontrolled or clinically significant cardiovascular disease including the following:
* Myocardial infarction within 6 months before screening.
* Unstable angina within 3 months before screening.
* New York Heart Association class III or IV congestive heart failure.
* History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes).
* Prior malignancy within the past 3 years, except for curatively treated basal or squamous cell skin cancer, non-muscle-invasive bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score 6 prostate cancer.
* History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention.
* History of stroke or intracranial hemorrhage within 6 months before first dose of study drug.
* Severe or debilitating pulmonary disease in the opinion of the treating investigator.
* Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
* Active fungal, bacterial and/or viral infection requiring systemic therapy.
* Underlying medical conditions that, in the investigator's opinion, will render the administration of study drug hazardous or obscure the interpretation of toxicity or AEs.
* Active infection with HIV, or serologic status reflecting active hepatitis B or C infection as follows:
* Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Patients with presence of HBcAb, but absence of HBsAg, are eligible if hepatitis B virus (HBV) DNA is undetectable (\< 20 IU), and if they are willing to undergo monitoring every 4 weeks for HBV reactivation.
* Presence of hepatitis C virus (HCV) antibody. Patients with presence of HCV antibody are eligible if HCV RNA is undetectable.
* Major surgery within 4 weeks of the first dose of study drug.
* Pregnant or lactating women.
* Left ventricular ejection fraction (LVEF) \<55% on screening echocardiogram.
* Vaccination or requirement for vaccination with a live vaccine within 28 days prior to the first dose of study drug or at any time during planned study treatment.
* Hypersensitivity to zanubrutinib, rituximab, cyclophosphamide, doxorubicin, vincristine, or prednisone.
* Requires ongoing treatment with a strong CYP3A inducer (Table 3).
* Concurrent participation in another therapeutic clinical trial.
* Active and/or ongoing autoimmune anemia and/or autoimmune thrombocytopenia (eg, idiopathic thrombocytopenia purpura).
* Requires ongoing treatment with warfarin or warfarin derivatives. DRUG: Zanubrutinib
Diffuse Large B-Cell Lymphoma, DLBCL - Diffuse Large B Cell Lymphoma
Diuretics Alone vs. Aortix Endovascular Device for Acute Heart Failure (DRAIN-HF)
Rubi Reyes-Fuentez - rubi@procyrion.com
NCT05677100
Inclusion Criteria (Randomized Study):
* Currently admitted to the hospital with a primary diagnosis of decompensated heart failure, irrespective of ejection fraction (EF);
* Patients should be on maximally tolerated diuretic therapy and not diuresing sufficiently before being enrolled in DRAIN-HF. After being up-titrated on diuretics, patients should be followed for at least 24 hours on the higher of: i) furosemide 80 mg IV bid or equivalent or ii) IV furosemide or equivalent IV loop diuretic at a dose 2.5 x total daily home dose of furosemide equivalents in 2 divided doses, as tolerated, patient must have: Urine Output \<1,500mL in a 12-hour period OR a Net Fluid Loss ≤375mL in a 12-hour period.
* Persistent signs and/or symptoms of congestion as evidenced by at least 2+ pitting edema, elevated jugular venous pressure \>12 cm water or ascites after treatment with IV diuretics per inclusion criterion 2.;
* Age \>21 years and able to provide written informed consent;
* Negative pregnancy test if patient is of child-bearing potential.
Exclusion Criteria (Randomized Study):
* Treatment with high dose IV inotropes within the last 48 hours prior to enrollment. High dose is defined as \>5 µg/kg/min dopamine OR \>5 µg/kg/min dobutamine OR \>0.375 µg/kg/min milrinone;
* Active and ongoing hypotension with a systolic blood pressure \<90 mmHg lasting more than 30 minutes or a mean arterial pressure (MAP) \<60 mmHg lasting more than 30 minutes at enrollment;
* Treatment with vasopressors (defined as phenylephrine, norepinephrine, epinephrine or, vasopressin) within 48 hours prior to enrollment;
* An estimated PASP of \>80 mmHg as measured on echocardiogram or echocardiographic evidence of primarily right heart failure;
* Acute kidney failure defined as an increase in serum creatinine to ≥4.0mg/dL (≥353.6 µmol/L) at enrollment;
* Evidence of contrast induced nephropathy, nephritis or nephrotic syndrome;
* Prior kidney transplant, single kidney, partial nephrectomy OR use of dialysis, continuous renal replacement therapy (CRRT) or ultrafiltration in the last 90 days prior to enrollment;
* Confirmed decompensated cirrhosis (defined as Child Pugh class B or C) or concern for shock liver (AST \> 1000U/L or total Bilirubin \> 5.0mg/dl) at enrollment;
* Presence of an active, uncontrolled infection that would preclude safe placement or removal of the device;
* Prior heart transplant or likely heart transplantation before the 30- day follow-up visit;
* Current or previous support with a durable LVAD at any time or planned LVAD insertion before the 30-day follow-up visit;
* Use of an intra-aortic balloon pump (IABP), extracorporeal membrane oxygenation (ECMO), or percutaneous ventricular assist devices (e.g. Impella or TandemHeart) within the last 30 days;
* Confirmed diagnosis of AL amyloidosis;
* Acute myocardial infarction Type 1 within 30 days of enrollment, or planned coronary revascularization in the next 30 days;
* Stroke within 30 days of enrollment;
* Severe Bleeding Risk (any of the following):
• Previous intracranial bleed unless there is documentation in the medical record (from a physician that is not part of the study) that the patient can safely use anticoagulation for 7 days,
• GI bleeding within 6 months requiring hospitalization and/or transfusion,
• Recent major surgery within 30 days if the surgical wound is judged to be associated with an increased risk of bleeding,
• Procedure with arterial ilio-femoral access \> 6 FR within 30 days,
• Platelet count \<75,000 cells/mm3,
• Uncorrectable bleeding diathesis or coagulopathy (e.g. INR ≥2 not due to anticoagulation therapy) or hypercoaguable state including HIT;
• Inability to tolerate anticoagulation therapy for up to 7 days. * Contraindicated Anatomy :
• Descending aortic anatomy that would prevent safe placement of the device \[\<18 mm or \>31 mm aorta diameter at deployment location (measured between the superior aspect of the T10 vertebra and superior aspect of the L1 vertebra)\],
• Ilio-femoral diameter or peripheral vascular anatomy that would preclude safe placement of a 21F (outer diameter) introducer sheath,
• Femoral artery depth inconsistent with use of closure device,
• Abnormalities or severe vascular disease that would preclude safe access and device delivery (e.g. aneurysm with thrombus, marked tortuosity, significant narrowing or inadequate size of the abdominal aorta, iliac or femoral arteries, or severe calcification),
• Known connective tissue disorder (e.g. Marfan Syndrome) or other aortopathy at risk of vascular injury,
• Any endovascular stent graft in the descending aorta. Any endovascular stent graft in the femoro-iliac vessels that is not well endothelialized and would preclude safe introduction/removal of the Aortix pump as demonstrated by imaging. * Known hypersensitivity or contraindication to study or procedure medications (e.g. anticoagulation therapy) or device materials (e.g. history of severe reaction to nickel or nitinol); * Participation in any other clinical investigation that is likely to confound study results or affect the study; * Poor health such that the patient is unable to undergo the Aortix device placement/retrieval and/or unlikely to be able to survive to the 30-day visit; * Unable or unwilling to undergo screening (imaging, PA Catheter placement), device implant and retrieval procedures or return for 30-day visit. Inclusion Criteria (Advanced Heart Failure Registry): * Currently admitted to the hospital with a primary diagnosis of decompensated HF, irrespective of ejection fraction (EF). * Patient has already been evaluated and indicated to receive an LVAD or heart transplant and will receive the LVAD or be listed for heart transplantation in the next 30 days if their congestion status and renal function improves. * Patient must have been treated with ≥ 80 mg IV furosemide bid or equivalent and have evidence of increasing diuretic dosing requirements over the past 12 months, as tolerated. * Must have evidence of refractoriness to medical management as documented by persistent signs and/or symptoms of congestion as evidenced by at least 2+ pitting edema, elevated jugular venous pressure \>12 cm water, or ascites after treatment with IV diuretics for a minimum of 24 hours. * Serum creatinine ≥ 2.0 mg/dL AND eGFR ≤ 45 ml/min/1.73m2 at time of enrollment * Age ≥ 21 years and able to provide written informed consent. * Negative pregnancy test if patient is of childbearing potential. Exclusion Criteria (Advanced Heart Failure Registry): * Treatment with high dose IV inotropes within 48 hours prior to enrollment. High dose is defined as any one of the following: \>5 µg/kg/min dopamine OR \>5 µg/kg/min dobutamine OR \>0.375 µg/kg/min milrinone. * Active and ongoing hypotension with a systolic blood pressure \<80 mmHg lasting more than 30 minutes or a mean arterial pressure (MAP) \<55 mmHg lasting more than 30 minutes at enrollment. * Treatment with vasopressors (defined as phenylephrine, norepinephrine, epinephrine or, vasopressin) within 48 hours prior to enrollment. * An estimated PASP of \>80 mmHg as measured on echocardiogram or echocardiographic evidence of primarily right heart failure. * Acute kidney failure defined as an increase in serum creatinine to ≥ 4.0mg/dL at enrollment. * Evidence of contrast-induced nephropathy, nephritis, or nephrotic syndrome. * Prior kidney transplant, single kidney, partial nephrectomy OR use of dialysis, continuous renal replacement therapy (CRRT), or ultrafiltration in the last 90 days prior to enrollment. * Confirmed decompensated cirrhosis (defined as Child Pugh class B or C) or concern for shock liver (AST \> 1000U/L or total Bilirubin \> 5.0mg/dl) at enrollment. * Presence of an active, uncontrolled infection that would preclude safe placement or removal of the device. * Current or previous support with a durable LVAD. * INTERMACS Profile 1 at enrollment. * Currently on mechanical ventilatory support. * Use of an extracorporeal membrane oxygenation (ECMO) or percutaneous ventricular assist device (e.g., Impella or TandemHeart) within the last 30 days. * Confirmed diagnosis of AL amyloidosis. * Acute myocardial infarction Type 1 within 30 days of enrollment or planned coronary revascularization in the next 30 days. * Stroke within 30 days of enrollment. * Severe Bleeding Risk (any of the following): * Previous intracranial bleed unless there is documentation in the medical record (from a physician that is not part of the study) that the patient can safely use anticoagulation for 7 days. * GI bleeding within 6 months requiring hospitalization and/or transfusion. * Recent major surgery within 30 days if the surgical wound is judged to be associated with an increased risk of bleeding. * Procedure with arterial ilio-femoral access \> 6 Fr within 30 days. * Platelet count \<75,000 cells/mm3 . * Uncorrectable bleeding diathesis or coagulopathy (e.g., INR≥ 2 not due to anticoagulation therapy) or hypercoagulable state including HIT. * Inability to tolerate anticoagulation therapy for up to 7 days. * Contraindicated Anatomy : * Descending aortic anatomy that would prevent safe placement of the device \[\<18 mm or \>31 mm aorta diameter at deployment location (measured between the superior aspect of the T10 vertebra and superior aspect of the L1 vertebra)\]. * Ilio-femoral diameter or peripheral vascular anatomy that would preclude safe placement of a 21 Fr (outer diameter) introducer sheath. * Femoral artery depth inconsistent with use of closure device. * Abnormalities or severe vascular disease that would preclude safe access and device delivery (e.g., aneurysm with thrombus; marked tortuosity; significant narrowing or inadequate size of the abdominal aorta, iliac, or femoral arteries; or severe calcification). * Known connective tissue disorder (e.g., Marfan Syndrome) or other aortopathy at risk of vascular injury. * Any endovascular stent graft in the descending aorta. Any endovascular stent graft in the femoro-iliac vessels that is not well endothelialized and would preclude safe introduction/removal of the Aortix pump as demonstrated by imaging. * Known hypersensitivity or contraindication to study or procedure medications (e.g., anticoagulation therapy) or device materials (e.g., history of severe reaction to nickel or nitinol). * Participation in any other clinical investigation that is likely to confound study results or affect the study. * Poor health such that the patient is unable to undergo the Aortix device placement/retrieval and/or unlikely to be able to survive to the 30-day visit. * Unable or unwilling to undergo screening, device implant and retrieval procedures, or return for 30-day visit.
• Previous intracranial bleed unless there is documentation in the medical record (from a physician that is not part of the study) that the patient can safely use anticoagulation for 7 days,
• GI bleeding within 6 months requiring hospitalization and/or transfusion,
• Recent major surgery within 30 days if the surgical wound is judged to be associated with an increased risk of bleeding,
• Procedure with arterial ilio-femoral access \> 6 FR within 30 days,
• Platelet count \<75,000 cells/mm3,
• Uncorrectable bleeding diathesis or coagulopathy (e.g. INR ≥2 not due to anticoagulation therapy) or hypercoaguable state including HIT;
• Inability to tolerate anticoagulation therapy for up to 7 days. * Contraindicated Anatomy :
• Descending aortic anatomy that would prevent safe placement of the device \[\<18 mm or \>31 mm aorta diameter at deployment location (measured between the superior aspect of the T10 vertebra and superior aspect of the L1 vertebra)\],
• Ilio-femoral diameter or peripheral vascular anatomy that would preclude safe placement of a 21F (outer diameter) introducer sheath,
• Femoral artery depth inconsistent with use of closure device,
• Abnormalities or severe vascular disease that would preclude safe access and device delivery (e.g. aneurysm with thrombus, marked tortuosity, significant narrowing or inadequate size of the abdominal aorta, iliac or femoral arteries, or severe calcification),
• Known connective tissue disorder (e.g. Marfan Syndrome) or other aortopathy at risk of vascular injury,
• Any endovascular stent graft in the descending aorta. Any endovascular stent graft in the femoro-iliac vessels that is not well endothelialized and would preclude safe introduction/removal of the Aortix pump as demonstrated by imaging. * Known hypersensitivity or contraindication to study or procedure medications (e.g. anticoagulation therapy) or device materials (e.g. history of severe reaction to nickel or nitinol); * Participation in any other clinical investigation that is likely to confound study results or affect the study; * Poor health such that the patient is unable to undergo the Aortix device placement/retrieval and/or unlikely to be able to survive to the 30-day visit; * Unable or unwilling to undergo screening (imaging, PA Catheter placement), device implant and retrieval procedures or return for 30-day visit. Inclusion Criteria (Advanced Heart Failure Registry): * Currently admitted to the hospital with a primary diagnosis of decompensated HF, irrespective of ejection fraction (EF). * Patient has already been evaluated and indicated to receive an LVAD or heart transplant and will receive the LVAD or be listed for heart transplantation in the next 30 days if their congestion status and renal function improves. * Patient must have been treated with ≥ 80 mg IV furosemide bid or equivalent and have evidence of increasing diuretic dosing requirements over the past 12 months, as tolerated. * Must have evidence of refractoriness to medical management as documented by persistent signs and/or symptoms of congestion as evidenced by at least 2+ pitting edema, elevated jugular venous pressure \>12 cm water, or ascites after treatment with IV diuretics for a minimum of 24 hours. * Serum creatinine ≥ 2.0 mg/dL AND eGFR ≤ 45 ml/min/1.73m2 at time of enrollment * Age ≥ 21 years and able to provide written informed consent. * Negative pregnancy test if patient is of childbearing potential. Exclusion Criteria (Advanced Heart Failure Registry): * Treatment with high dose IV inotropes within 48 hours prior to enrollment. High dose is defined as any one of the following: \>5 µg/kg/min dopamine OR \>5 µg/kg/min dobutamine OR \>0.375 µg/kg/min milrinone. * Active and ongoing hypotension with a systolic blood pressure \<80 mmHg lasting more than 30 minutes or a mean arterial pressure (MAP) \<55 mmHg lasting more than 30 minutes at enrollment. * Treatment with vasopressors (defined as phenylephrine, norepinephrine, epinephrine or, vasopressin) within 48 hours prior to enrollment. * An estimated PASP of \>80 mmHg as measured on echocardiogram or echocardiographic evidence of primarily right heart failure. * Acute kidney failure defined as an increase in serum creatinine to ≥ 4.0mg/dL at enrollment. * Evidence of contrast-induced nephropathy, nephritis, or nephrotic syndrome. * Prior kidney transplant, single kidney, partial nephrectomy OR use of dialysis, continuous renal replacement therapy (CRRT), or ultrafiltration in the last 90 days prior to enrollment. * Confirmed decompensated cirrhosis (defined as Child Pugh class B or C) or concern for shock liver (AST \> 1000U/L or total Bilirubin \> 5.0mg/dl) at enrollment. * Presence of an active, uncontrolled infection that would preclude safe placement or removal of the device. * Current or previous support with a durable LVAD. * INTERMACS Profile 1 at enrollment. * Currently on mechanical ventilatory support. * Use of an extracorporeal membrane oxygenation (ECMO) or percutaneous ventricular assist device (e.g., Impella or TandemHeart) within the last 30 days. * Confirmed diagnosis of AL amyloidosis. * Acute myocardial infarction Type 1 within 30 days of enrollment or planned coronary revascularization in the next 30 days. * Stroke within 30 days of enrollment. * Severe Bleeding Risk (any of the following): * Previous intracranial bleed unless there is documentation in the medical record (from a physician that is not part of the study) that the patient can safely use anticoagulation for 7 days. * GI bleeding within 6 months requiring hospitalization and/or transfusion. * Recent major surgery within 30 days if the surgical wound is judged to be associated with an increased risk of bleeding. * Procedure with arterial ilio-femoral access \> 6 Fr within 30 days. * Platelet count \<75,000 cells/mm3 . * Uncorrectable bleeding diathesis or coagulopathy (e.g., INR≥ 2 not due to anticoagulation therapy) or hypercoagulable state including HIT. * Inability to tolerate anticoagulation therapy for up to 7 days. * Contraindicated Anatomy : * Descending aortic anatomy that would prevent safe placement of the device \[\<18 mm or \>31 mm aorta diameter at deployment location (measured between the superior aspect of the T10 vertebra and superior aspect of the L1 vertebra)\]. * Ilio-femoral diameter or peripheral vascular anatomy that would preclude safe placement of a 21 Fr (outer diameter) introducer sheath. * Femoral artery depth inconsistent with use of closure device. * Abnormalities or severe vascular disease that would preclude safe access and device delivery (e.g., aneurysm with thrombus; marked tortuosity; significant narrowing or inadequate size of the abdominal aorta, iliac, or femoral arteries; or severe calcification). * Known connective tissue disorder (e.g., Marfan Syndrome) or other aortopathy at risk of vascular injury. * Any endovascular stent graft in the descending aorta. Any endovascular stent graft in the femoro-iliac vessels that is not well endothelialized and would preclude safe introduction/removal of the Aortix pump as demonstrated by imaging. * Known hypersensitivity or contraindication to study or procedure medications (e.g., anticoagulation therapy) or device materials (e.g., history of severe reaction to nickel or nitinol). * Participation in any other clinical investigation that is likely to confound study results or affect the study. * Poor health such that the patient is unable to undergo the Aortix device placement/retrieval and/or unlikely to be able to survive to the 30-day visit. * Unable or unwilling to undergo screening, device implant and retrieval procedures, or return for 30-day visit.
DEVICE: Aortix System
Heart Failure, Cardiorenal Syndrome, Cardio-Renal Syndrome, ADHF, Heart Failure, Systolic, Heart Failure, Diastolic, Heart Failure, With Decompensation, Heart Failure, Congestive
mechanical circulatory support, percutaneous
A Phase 2 Study of PTX 100 in Patients With Relapsed/Refractory CTCL
Upaly Bahadure - upaly@ptxtherapeutics.com
NCT06854653
Inclusion Criteria:
• Adult patient ≥18 years of age at the time of signing the informed consent.
• Patient is capable of giving adequate signed informed consent
• Have a confirmed diagnosis of CTCL with histological confirmation
• Patients must have greater than or equal to Stage Ib disease.
• Has received and failed (or intolerant of) at least 2 prior lines of prior systemic therapy for their disease.
• Has measurable disease defined by at least one of the following, within 28 days prior to start of study treatment: by evaluable by mSWAT or quantifiable by flow cytometry or morphology in blood or measurable by Lugano Criteria.
• On a stable dose of systemic corticosteroid (\< 10 mg prednisone or equivalent) are permitted. Participants on a stable dose of topical corticosteroids are permitted.
• Washout period- must be 2 weeks (4 weeks for monoclonal antibodies) or 5 -half-lives (whichever is longer) since any prior anti-cancer therapy.
• Must be human T-cell lymphotropic virus type 1 (HTLV1) negative.
• Has an ECOG PS of 0 to 2.
• Life expectancy of 3 months or greater
• Has adequate bone marrow function.
• Has adequate hepatic function.
• Has adequate Renal function.
• Has adequate coagulation function.
• Patients with Human Immunodeficiency virus (HIV) must be on established and stable effective anti-retroviral therapy for at least 4 weeks and have an HIV viral load of less than 400 copies/mL.
• Male patients are eligible to participate if they agree to use a highly effective contraception during the treatment period and for at least 3 months after the last dose of study treatment and refrain from donating sperm during this period.
• Female patients are eligible to participate if they are not pregnant, not breastfeeding, and at least one of the following conditions applies: -Not a woman of childbearing potential (WOCBP). * OR * A WOCBP who agrees to use a contraceptive method that is highly effective (with a failure rate of \< 1% per year) or be abstinent from heterosexual intercourse as their preferred method and usual lifestyle, beginning the time of informed consent, during the treatment period and for at least 3 months after the last dose of study treatment.
• A WOCBP must have a negative serum pregnancy within 72 hours of the first dose of study treatment.
• Must be willing and able to adhere to the study as judged by the Investigator.
Exclusion Criteria:
• Patients with known central nervous system involvement.
• Patients who require the use of strong inhibitors or inducers of CYP enzymes or transporters (e.g., CYP3A4, 2D6, 2C19) or (P-gp, BCRP, OATP1B1, OATP1B3, OAT1. OAT3, OCT2, MATE1 and MATE2-K). Patients who are receiving these medications at Screening can be enrolled into the trial if they discontinue them for at least 14 days or 5 half-lives, whichever is longer, before they commence PTX-100. An alternative pharmacological treatment should be instituted by the treating clinician based on clinical judgement.
• Significant cardiovascular disease. A history of, or concurrent interstitial lung disease or severely impaired lung function. 5\. Active viral, bacterial, fungal infection or other serious infection requiring ongoing systemic treatment. Routine antimicrobial prophylaxis is permitted. 6\. Medical history of another malignant tumor within the past 5 years. Exceptions are patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ who have undergone curative therapy with no evidence of disease. 7\. On an immunomodulatory drug for concomitant or intercurrent conditions or who have received any of these agents within 4 weeks of baseline. 8\. Patients with active viral (any etiology) hepatitis are excluded. However, patients with serologic evidence of chronic hepatitis B virus (HBV) infection (defined by a positive hepatitis B surface antigen test and a positive anti-hepatitis core antigen antibody test) who have a viral load below the limit quantification (HBV deoxyribose nucleic acid titer \< 1000 cps/mL or 200 IU/mL) and are not currently on viral suppressive therapy may be eligible and should be discussed with the Medical Monitor. Patients with a history of hepatitis C virus infection who have completed curative antiviral treatment and have a viral load below the limit of quantification may be eligible and should be discussed with the Medical Monitor. 9\. A history or current evidence of any condition, laboratory abnormality or other circumstance that might confound the results of the study or interfere with patient participation for the full duration of the study. 10\. Prior allogeneic or autologous hematopoietic transplantation 11. Has a known psychiatric disorder that would interfere with compliance with the requirements of the study. 12\. Is a consumer of illicit or recreational drugs or has a recent history (within the last year) of drug or alcohol abuse or dependence that in the judgment of the Investigator, would interfere with compliance with the requirements of the study.
DRUG: PTX-100
CTCL
Relapsed or refractory Cutaneous T Cell Lymphoma, CTCL, PTX-100, Mycosis Fungoides, Sezary Syndrome, T Cell Lymphoma, Non-Hodgkin Lymphoma, Cutaneous Lymphoma
CardiolRx in Recurrent Pericarditis (MAVERIC Phase-3) (MAVERIC)
Andrea B Parker, MSc., PhD - andrea.parker@cardiolrx.com
NCT06708299
Inclusion Criteria:
• Patients 18 years of age or older
• A history of recurrent pericarditis with stable disease and currently being treated with an IL-1 blocker, scheduled to be discontinued. Stable disease is defined as: * treatment with an IL-1 blocker for at least 12 months, * free of pericarditis recurrence for at least 6 months and this recurrence, if present, must have occurred in the setting of an interruption or tapering of an IL-1 blocker; and * treatment with an unchanged dose and regimen of on an IL-1 blocker for at least 3 months prior to randomization.
• Pericarditis pain les or equal than 2 on the 11-point Numerical Rating Scale (NRS) for at least 7 days prior to randomization (Visit 1, Day 1)
• C-Reactive Protein (CRP) \< 1.0 mg/dL during screening within 7 days prior to randomization (Visit 1, Day 1).
• Patients who have had a vasectomy or who are willing to use double barrier contraception methods with partners of childbearing potential during the conduct of the trial and for 2 months after the last dose of trial therapy.
• Patients of childbearing potential willing to use an acceptable method of contraception starting with trial therapy administration and for a minimum of 2 months after trial completion. Otherwise, these patients must be postmenopausal (at least 1 year absence of vaginal bleeding or spotting and confirmed by follicle stimulating hormone \[FSH\] ≥ 40 mIU/mL \[or ≥ 40 IU/L\] if less than 2 years postmenopausal) or be surgically sterile. Acceptable birth control methods that result in a failure rate of less than 1 % include oral, intravaginal or transdermal combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation; oral, injectable or implantable progestogen-only hormonal contraception associated with inhibition of ovulation; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); using double-barrier contraception methods with their partners; bilateral tubal occlusion; vasectomised partner; sexual abstinence.
Exclusion Criteria:
• Pericarditis recurrence(s) during IL-1 blocker treatment without interruption or tapering of the IL-1 blocker
• Diagnosis of pericarditis that is secondary to specific prohibited etiologies, including tuberculosis (TB); neoplastic, purulent, or radiation etiologies; post-thoracic blunt trauma (e.g., motor vehicle accident); systemic autoimmune disease (e.g., systemic lupus erythematosus)
• Primary diagnosis of myocarditis (diagnosis of myopericarditis is accepted)
• Estimated glomerular filtration rate (eGFR) \< 30 mL/min during screening within 7 days prior to randomization (Visit 1, Day 1)
• Elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 5 times the upper limit of normal (ULN) or ALT or AST \> 3x ULN plus bilirubin \> 2x ULN during screening within 7 days prior to randomization (Visit 1, Day 1).
• Sepsis, defined as documented bacteremia during screening within 7 days prior to randomization (Visit 1, Day 1) or other untreated or uncontrolled bacterial infection\*
• Prior history of sustained ventricular arrhythmia(s)
• History of diagnosed long QT syndrome
• QTc interval \> 480 msec (biologically female) or \> 470 msec (biologically male) (please refer to Section 9.2.3 for bundle branch block, bifascicular block and paced rhythm correction) or second or third degree atrioventricular (AV) block in a patient without an implanted functioning pacemaker device during screening within 7 days prior to randomization (Visit 1, Day 1)
• Showing suicidal tendency during the last 12 months, as defined by answering "yes" to question 4 or 5 of the Columbia Suicide Severity Rating Scale (C-SSRS), administered during screening within 7 days prior to randomization (Visit 1, Day 1)
• Participation in a clinical trial in which an investigational drug or device was administered within 30 days of screening or within 5 half-lives of the previous study drug, whichever is longer
• Inability or unwillingness to give informed consent
• Ongoing drug or alcohol abuse in the opinion of the investigator
• On any cannabinoid during the past month or unwilling to stay abstinent from all cannabis products for the duration of the trial
• Pregnant or breastfeeding
• Current diagnosis of active cancer, with the exception of non-melanoma skin cancer
• Any factor, which would make it unlikely that the patient can comply with the trial procedures
• Moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment
• Has received systemic immunomodulatory agents as below prior to randomization:
• Methotrexate (within 2 weeks)
• Azathioprine, mycophenolate mofetil, cyclosporine, tacrolimus, sirolimus, or mercaptopurine (within 24 weeks)
• Canakinumab, TNF inhibitors, IL-6 inhibitors, or janus-activating kinase inhibitors (within 12 weeks)
• Intravenous immune globulin (IVIG) (within 8 weeks)
• Corticosteroids (within 4 weeks)
• Known hypersensitivity to the active substance or any of the excipients of the trial
DRUG: CardiolRx
Recurrent Pericarditis
IL-1 blocker-dependent recurrent pericarditis, pharmaceutically cannabidial
Testing Teclistamab (TECVAYLI) in Combination With Iberdomide for Relapsed or Refractory Multiple Myeloma
ctrrecruit@vcu.edu
NCT06465316
Inclusion Criteria:
* Patients must have histologically or cytologically confirmed multiple myeloma (MM), as defined in the International Myeloma Working Group (IMWG) criteria
* If patients have undergone autologous stem cell transplant (SCT), day 0 of SCT must be \> 100 days to be eligible for the study
* Patients must have had disease progression after ≥ 4 prior lines of anti-myeloma treatments including one proteasome inhibitor (e.g., bortezomib, carfilzomib, ixazomib), one immunomodulatory imide drug (ImiD) (e.g., thalidomide, lenalidomide, pomalidomide \[POM\]), and one anti-CD38 monoclonal antibody (e.g., daratumumab, isatuximab)
* Patients must have measurable disease, defined as:
* Serum M-protein ≥ 0.5 g/dL (≥ 5 g/L)
* Urine M-protein ≥ 200 mg/24 h
* Serum free light chain (FLC) assay: "involved" FLC level ≥ 10 mg/dL (≥ 100 mg/L) and an abnormal serum free light chain ratio (\< 0.26 or \> 1.65)
* Note: Patients with non-secretory disease will be allowed to participate
* Age ≥ 18 years
* Because no dosing or adverse event data are currently available on the use of iberdomide in combination with teclistamab in patients \< 18 years of age, children are excluded from this study
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60)
* Hemoglobin ≥ 7.0 g/dL (≤ 28 days prior to registration) (Without growth factor support, blood transfusion, or platelet stimulating agents for the past 7 days, excluding erythropoietin)
* Absolute neutrophil count ≥ 1,000/mcL (≤ 28 days prior to registration) (Without growth factor support, blood transfusion, or platelet stimulating agents for the past 7 days, excluding erythropoietin)
* Platelets ≥ 50,000/mcL (≤ 28 days prior to registration) (Without growth factor support, blood transfusion, or platelet stimulating agents for the past 7 days, excluding erythropoietin)
* Total bilirubin ≤ 2 x institutional upper limit of normal (ULN) (≤ 28 days prior to registration)
* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 x institutional ULN (≤ 28 days prior to registration)
* Estimated glomerular filtration rate (eGFR) \> 30 mL/min (≤ 28 days prior to registration)
* Spot urine (albumin/creatine ratio) ≤ 500mg/g (56 mg/mmol) OR urine dipstick negative/trace (if \> 1+ only eligible if confirmed ≤ 500 mg/g \[56 mg/mmol\] by albumin/creatinine ratio \[spot urine from first void\]) (≤ 28 days prior to registration)
* Note: Laboratory results obtained during screening should be used to determine eligibility criteria. In situations where laboratory results are outside the permitted range, the investigator may re-test the subject and the subsequent within range screening result may be used to confirm eligibility
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with treated brain metastases are eligible if follow-up brain imaging done a minimum of 28 days after completion of central nervous system (CNS)-directed therapy shows no evidence of progression
* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better
* Based on the mechanism of action, teclistamab may cause fetal harm when administered to a pregnant woman. Females of child-bearing potential (FCBP): should use effective contraception during treatment with teclistamab and for 5 months after the last dose. FCBP should not breast feed during treatment with teclistamab and for 5 months after the last dose. Should a FCBP become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. The effects of iberdomide on the developing human fetus are unknown. However, IMiDs are known to be teratogenic. FCBP must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days prior to starting iberdomide, and again within 24 hours. FCBP must either commit to continued abstinence from heterosexual intercourse or begin two acceptable methods of birth control-one highly effective method and one additional effective method-at the same time, at least 28 days before starting iberdomide, while taking iberdomide, and for 28 days following discontinuation from the study. Examples of highly effective methods are intrauterine device, hormonal contraceptives, tubal ligation, or partner's vasectomy. Examples of barrier method are male condom, diaphragm, or cervical cap. FCBP must also agree to ongoing pregnancy testing. Men must practice complete abstinence or agree to use a condom during sexual contact with FCBP while participating in the study, during dose interruptions, and for at least 28 days following discontinuation from the study, even if he has undergone a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risk of fetal exposure
* Men must agree to abstain from donating and semen or sperm while taking iberdomide, during dose interruptions, and for at least 28 days after the last dose of iberdomide. FCBP must agree not to donate eggs (ova, oocytes) for the purpose of reproduction during this period
* All patients must agree to abstain from donating blood products while taking iberdomide and for at least 28 days after the last dose of iberdomide
* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study subjects
* Willingness to adhere to the study visit schedule and other protocol requirements and provide mandatory blood and bone marrow specimens for correlative research
* Willingness to return to the enrolling institution for follow-up
Exclusion Criteria:
* Patients who have active plasma cell leukemia, active amyloid light chain (AL) (primary) amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, myeloma protein, and skin changes), and Waldenstrom macroglobulinemia are ineligible
* If a patient develops recurrent/refractory (R/R) disease while receiving the most recent line of therapy, there is no need for a washout period
* Patients who have had prior anti-BCMA directed bispecific antibody (BsAb) therapy exposure (prior treatment with anti-BCMA directed antibody drug conjugate, anti-BCMA-directed chimeric antigen receptor \[CAR\] T cell therapy, and prior non-BCMA-targeting BsAb are permitted)
* Patients who have had prior treatment with a cereblon E3 ligase modulator, including mezigdomide, iberdomide, and CFT7455 (all currently in clinical development)
* Patients who received plasmapheresis ≤ 7 days prior to registration
* Patients who received a prior allogeneic SCT. Autologous SCT is allowed
* Patients who received a live or live-attenuated vaccine ≤ 30 days prior to registration. Patients are allowed to receive a coronavirus disease 2019 (COVID-19) vaccine at any timepoint during protocol treatment
* Systemic active infection requiring treatment
* Any unresolved toxicity ≥ grade 2 from previous treatment except for alopecia or peripheral neuropathy up to grade 2
* Patients who have had any major surgery ≤ 4 weeks prior to registration
* Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make this protocol unreasonably hazardous
* Patients with evidence of active mucosal or internal bleeding
* Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. Stable chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if participant otherwise meets entry criteria
* Patients with known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to teclistamab or iberdomide, or any of the components of the study treatment
* Patients who are taking any anticancer therapy other than hormonal therapy (for prostrate or breast cancer) and palliative radiotherapy (defined as radiation to ≤ 3 sites of active multiple myeloma)
* Patients who require immunosuppressive medications including, but not limited to, systemic corticosteroids at doses exceeding 10 mg/day of prednisone or equivalent. Use of immunosuppressive medications for the management of iberdomide-related adverse events (AEs) or in subjects with contrast allergies is acceptable. In addition, use of inhaled, topical, intranasal corticosteroids or local steroid injection (e.g., intra-articular injection) is permitted. Temporary use of corticosteroids for concurrent illnesses (e.g., food allergies, computed tomography \[CT\] scan contrast hypersensitivity, pneumonia, etc.) are acceptable
* Patients who require medications that are strong inhibitors or inducers of CYP3A4/5
* Patients who are receiving any other investigational agents
* Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
* Pregnant women are excluded from this study because iberdomide is a thalidomide analog and thalidomide is a known human teratogen. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with iberdomide, breastfeeding should be discontinued if the mother is treated with iberdomide. These potential risks may also apply to other agents used in this study
* Patients who are unable or unwilling to undergo protocol required thromboembolism prophylaxis are excluded PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Bone Marrow Biopsy, PROCEDURE: Computed Tomography, DRUG: Iberdomide, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Positron Emission Tomography, DRUG: Teclistamab
Recurrent Multiple Myeloma, Refractory Multiple Myeloma