StudyFinder
Search Results
631 Study Matches
Adding Nivolumab to Usual Treatment for People With Advanced Stomach or Esophageal Cancer, PARAMUNE Trial
ctrrecruit@vcu.edu
PHASE2
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
NA
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 ETI or ivacaftor 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)
• 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
Self-collection for HPV Testing to Improve Cervical Cancer Prevention (SHIP) Trial (LMI-001-A-S02)
ctrrecruit@vcu.edu
NA
NCT06611553
Inclusion Criteria:
* Willingness and ability to provide a documented informed consent
* Is 25 years or older
* Has an intact cervix
* Has had a referral for colposcopy and/or cervical excisional procedure in which routine cervical cancer screening has included HPV testing (HPV primary screening, co-testing, or atypical squamous cell of undetermined significance \[ASC-US\] cytology triage) or abnormal cytology performed within the past 12 months preceding the referral visit
* Willing and able to undergo colposcopy, and if clinically indicated for standard of care (SOC) purposes, a biopsy, endocervical curettage, and/or a cervical excisional procedure, as applicable
Exclusion Criteria:
* Is pregnant when presenting for the referral visit or gave birth within the past 3 months
* Has a known history of excisional or ablative therapy to the cervix (e.g., loop electrosurgical excision procedure \[LEEP\], cone biopsy, cervical laser surgery, cryotherapy, thermal ablation) in the last 12 months prior to the referral visit
* Has had a complete or partial hysterectomy, either supracervical or involving removal of the cervix, via self-report or confirmation via medical records
* Known medical conditions that, in the opinion of the investigator, preclude study participation
* Previous participation in the SHIP Trial. Participation is defined as completing the self-collection
* Is experiencing unusual bleeding or pelvic pain PROCEDURE: Biospecimen Collection, PROCEDURE: Cervical Biopsy, PROCEDURE: Colposcopy, OTHER: Electronic Health Record Review, PROCEDURE: Endocervical Curettage, PROCEDURE: Excision, PROCEDURE: HPV Self-Collection, PROCEDURE: Human Papillomavirus Test, OTHER: Questionnaire Administration, OTHER: Survey Administration
Cervical Carcinoma, Human Papillomavirus Infection
Testing the Safety of the Anti-cancer Drugs Tazemetostat and Belinostat in Patients With Lymphomas That Have Resisted Treatment
ctrrecruit@vcu.edu
PHASE1
NCT05627245
Inclusion Criteria:
* DOSE ESCALATION PHASE: Patients with relapsed or refractory non-Hodgkin lymphoma including both B-cell non-Hodgkin lymphoma (NHL) and T-cell NHL. Refractory cutaneous T-cell lymphoma (CTCL) will be allowed if greater or equal to stage 1B and have previously failed two systemic therapies
* DOSE EXPANSION PHASE: Patients with relapsed or refractory follicular, transformed lymphoma or germinal center B-cell diffuse large B-cell Lymphoma (GCB-DLBCL) as defined by Hans criteria, as well as T-cell lymphomas. For patients with B-cell lymphomas, equal numbers of patients will be enrolled onto one of 2 arms: (1) mutated EZH2 or (2) wild-type EZH2. EZH2 mutations will be identified by polymerase chain reaction (PCR)
* Patients must not be eligible for, or have refused, stem cell transplantation or chimeric antigen receptor T-cell (CAR T-cell) therapy
* Patients who have undergone 1-5 prior treatments of any type (progression after transplant/cellular therapy allowed) are eligible
* Patients must have measurable disease according to the Lugano classification
* Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of tazemetostat in combination with belinostat 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 \>= 1,000/mcL
* If there is documented lymphomatous involvement of the bone marrow as assessed by bone marrow biopsy within 90 days prior to registration, participants should have: absolute neutrophil count (ANC) \>= 0.75 × 10\^9/L
* Platelets \>= 75,000/mcL
* If there is documented lymphomatous involvement of the bone marrow as assessed by bone marrow biopsy within 90 days prior to registration, participants should have: platelets \>= 50 x 10\^9/L
* Total bilirubin =\< 1.5 institutional upper limit of normal (ULN); unless due to Gilbert's disease, hemolysis, or lymphomatous involvement of liver, in which case total bilirubin should be =\< 5 x institutional ULN
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional ULN; unless due to Gilbert's disease, hemolysis, or lymphomatous involvement of liver, in which case AST(SGOT)/ALT(SGPT) should be =\< 5 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 treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
* 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 whose lymphoma has transformed from a less aggressive histology remain eligible
* Patients should be New York Heart Association Functional Classification of class II or better
* Patients must have a QT interval corrected by Fridericia's formula (QTcF) =\< 450 msec
* Able to swallow and retain orally-administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption, such as malabsorption syndrome or major resection of the stomach or bowels
* The effects of tazemetostat and belinostat on the developing human fetus are unknown. For this reason, women of child-bearing potential must agree to use two reliable methods of contraception simultaneously prior to study entry and for the duration of study participation and for 6 months after the last dose of the study treatment. 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 3 months after completion of tazemetostat and belinostat administration. Male participants must not donate semen or sperm from first dose of study drug, during study treatment (including during dose interruptions), and for 3 months after study drug discontinuation
* 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
* Patients that have received prior chemotherapy or radiotherapy must have completed their last treatment at least 2 weeks before entering the study. Rituximab given between EZH2 analysis and initiation of study drugs will be allowed
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
* Patients with active central nervous system (CNS) metastases, including lymphomatous meningitis, as the study drugs are not known to effectively treat CNS disease
* History of allergic reactions attributed to belinostat or tazemetostat, or to compounds of similar chemical or biologic composition to these agents
* Patients receiving any medications or substances that are strong or moderate inhibitors or inducers of CYP3A4 within 14 days prior to study treatment are ineligible. Patients receiving strong UGT1A1 inhibitors are ineligible due to expected increased exposure to belinostat and potential for increased toxicity. Because the list of these agents is 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
* Patients with known UGT1A1 genetic polymorphisms, such as UGT1A1\*28, are excluded as they can have reduced UGTA1A activity and may be at risk for increased belinostat exposure
* Patients with uncontrolled intercurrent illness
* Pregnant women are excluded from this study because belinostat, as an HDAC inhibitor, and tazemetostat, as an EZH2 inhibitor, both have 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 belinostat and tazemetostat, breastfeeding should be discontinued if the mother is treated with belinostat and tazemetostat. Women of childbearing potential must have negative urine or serum pregnancy test to be eligible for this study
* Systemic steroids that have not been stabilized to the equivalent of =\< 10 mg/day prednisone prior to the start of the study drugs and throughout the study. Patients are allowed to receive dexamethasone as premedication during belinostat infusion
* Has thrombocytopenia, neutropenia, or anemia of grade \>= 3 (per Common Terminology Criteria for Adverse Events \[CTCAE\] 5.0 criteria) or any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS)
* Has abnormalities known to be associated with MDS (e.g. 5q deletion \[del 5q\], chromosome 7 abnormality \[chr 7 abn\]) and multiple primary neoplasms (MPN) (e.g. JAK2 V617F) observed in cytogenetic testing and deoxyribonucleic acid (DNA) sequencing
* Has a prior history of T lymphoblastic lymphoma/T acute lymphoblastic leukemia (T-LBL/T-ALL) DRUG: Belinostat, PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, OTHER: Pharmacokinetic Study, PROCEDURE: Positron Emission Tomography and Computed Tomography Scan, DRUG: Tazemetostat
Recurrent B-Cell Non-Hodgkin Lymphoma, Recurrent Diffuse Large B-Cell Lymphoma Germinal Center B-Cell Type, Recurrent Follicular Lymphoma, Recurrent Non-Hodgkin Lymphoma, Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma, Recurrent T-Cell Non-Hodgkin Lymphoma, Recurrent Transformed Non-Hodgkin Lymphoma, Refractory B-Cell Non-Hodgkin Lymphoma, Refractory Diffuse Large B-Cell Lymphoma Germinal Center B-Cell Type, Refractory Follicular Lymphoma, Refractory Non-Hodgkin Lymphoma, Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma, Refractory T-Cell Non-Hodgkin Lymphoma, Refractory Transformed Non-Hodgkin Lymphoma
A Study of Emapalumab for Pediatric Aplastic Anemia
Andromachi Scaradavou, MD - ScaradaA@mskcc.org
PHASE2
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 LYL314 in Aggressive Large B-Cell Lymphoma
Lyell Immunopharma Inc. - clinicaltrials@lyell.com
PHASE1
NCT05826535
Inclusion Criteria:
• Age 18 years or older at time of informed consent
• Willing and able to provide written informed consent
• Histologically confirmed aggressive NHL, including the following types defined by the World Health Organization (WHO 2017): * DLBCL * DLBCL arising from follicular lymphoma (transformed FL, tFL) * Primary mediastinal (thymic) large B-cell lymphoma (PMBCL) * High-grade large B-cell lymphoma with or without MYC and BCL2 and/or BCL6 rearrangement (HGBL) * Grade 3B follicular lymphoma/Large cell follicular lymphoma (FL3B)
• Received at least two prior lines of therapy for Cohorts 1, 2, and 4 and one prior line of therapy for Cohort 3. Prior therapy must have included: * Anti-CD20 monoclonal antibody, and * An anthracycline containing chemotherapy regimen * Participants with tFL must have received at least one of their prior lines of therapy after transformation to DLBCL 4b. Cohort 5 (High-risk first-line) participants must have high-risk large B-cell lymphoma
• Relapsed or refractory disease, defined by the following: * Disease progression after last regimen (including salvage therapy after autologous stem cell transplantation \[ASCT\]). In participants who have only received front-line therapy, progression should be ≤ 12 months of first-line therapy (applicable for Cohort 3) * In patients who received one line of therapy, refractory disease is defined as failure to achieve at least a PR after at least 4 cycles of therapy (applicable for Cohort 3) * In patients who received two or more lines of therapy (Cohorts 1, 2, and 4), refractory disease is defined as failure to achieve a CR to last line of therapy (including CAR T and/or salvage therapy).
• At least 1 measurable lesion (per Lugano classification). Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 or ECOG 0 to 2 (Cohort 5)
• Absolute neutrophil count (ANC) ≥ 1000/uL
• Platelet count ≥ 50,000/uL
• Absolute lymphocyte count (ALC) ≥ 200/uL Other protocol-defined criteria apply.
Exclusion Criteria:
• History of malignancy other than non-melanoma skin cancer or carcinoma in situ (e.g., cervix, bladder, breast) unless disease-free for at least 3 years. Participants who have received therapy for a prior malignancy within the prior 3 years, e.g., in the adjuvant setting, are not excluded
• Active central nervous system (CNS) involvement by malignancy on magnetic resonance imaging (MRI) or by lumbar puncture. Participants with prior evidence of brain metastasis treated at least 8 weeks prior to enrollment will not be excluded for participation if CNS disease is deemed stable at the time of study enrollment
• History of cardiac lymphoma involvement or Epstein-Barr virus (EBV)+ lymphoma
• Ongoing or impending oncologic emergency (e.g., tumor mass effect, tumor lysis syndrome, known vascular invasion)
• Received the following therapies in the specified time frame prior to enrollment/leukapheresis
• Any systemic therapy within 2 weeks
• Any systemic inhibitory/stimulatory immune checkpoint molecule therapy within 3 half-lives prior to enrollment (e.g., ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists)
• Fludarabine within 12 weeks
• Alemtuzumab, bendamustine or antithymocyte globuline (ATG) within 6 months
• Any T cell engager/bispecific antibody therapy such as CD20/CD3 or CD19/CD3 bispecific antibodies within 4 weeks
• Any experimental therapy within 4 weeks or 5 half-lives (whichever is shorter)
• Received radiation therapy within 3 weeks prior to enrollment/leukapheresis
• Experiencing non-hematologic toxicities due to prior therapy. Exceptions include: stable and recovered to grade ≤ 1 or non-clinically significant toxicities such as (1) alopecia, (2) toxicities where Grade 2 is solely defined by participant receiving hormone replacement therapy for endocrinopathies resulting from previous checkpoint inhibitor therapy, (3) Grade 2 lymphopenia, and (4) hearing loss or Grade 2 neuropathy associated with prior treatment with taxanes or platinating agents
• History of allogeneic stem cell or solid organ transplantation
• Receipt of autologous stem cell transplantation within 6 weeks prior to enrollment/leukapheresis
• History of prior genetically modified cell therapy 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). For all other CAR T cell therapy treatments, discussion with the Sponsor's Medical Monitor is required
• Primary immunodeficiency
• History of autoimmune disease (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years. Participants who have other autoimmune condition(s) considered to be associated with underlying malignancy may be enrolled in the study after discussion with and approval of the Medical Monitor. Other protocol-defined criteria apply.
DRUG: LYL314, 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, High-grade B-cell lymphoma, HGBL, 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
PHASE2
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.
* Transformed NLPHL, concerns of the treating physician of an occult transformation or concerns of the treating physician that the patient needs cytotoxic therapy.
* 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
A Study of Daratumumab-Based Therapies in Participants With Amyloid Light Chain (AL) Amyloidosis (AQUARIUS)
Study Contact - Participate-In-This-Study1@its.jnj.com
PHASE2
NCT05250973
Inclusion Criteria:
* Cohort 1: Cardiac involvement (amyloid light chain \[AL\] amyloidosis Mayo Cardiac Stage II and Stage IIIa) with or without other organ(s) involved; Cohort 2: One or more organs impacted by systemic AL amyloidosis according to consensus guidelines
* Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1 or 2
* A female participant of childbearing potential must have a negative serum or urine test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study
* A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 6 months after receiving the last dose of cyclophosphamide or 100 days after discontinuation of daratumumab, whichever is longer
* Cohort 2 only: self-identified racial and ethnic minorities, including Black or African American
* Measurable disease at screening defined by one of the following:
Difference between iFLC and uninvolved FLC (dFLC) \>= 40mg/L per central laboratory Serum involved free light chain (iFLC) \>= 40 mg/L with an abnormal kappa:lambda ratio Serum M-protein \>= 0.5 g/dL
Exclusion Criteria:
* Prior therapy for systemic AL amyloidosis or multiple myeloma including medications that target cluster of differentiation 38 (CD38), with the exception of 160 milligrams(mg) dexamethasone or equivalent corticosteroid maximum exposure prior to randomization/enrollment
* Previous or current diagnosis of symptomatic multiple myeloma, including the presence of lytic bone disease, plasmacytomas, \>=60% plasma cells in the bone marrow, or hypercalcemia related to myeloma.
* Participant received any of the following therapies:
• treatment with an investigational drug or used an invasive investigational medical device within 14 days or at least 5 half-lives, whichever is less;
• vaccinated with an investigational vaccine (except for COVID-19) live, attenuated or replicating viral vector vaccines less than (\<) 4 weeks prior to randomization/enrollment. Participants who are taking strong Cytochrome P450 3A4(CYP3A4) inducers must discontinue their use at least 5 half-lives prior to the first dose of bortezomib * Stem cell transplantation -Planned stem cell transplant during the first 9 cycles of protocol therapy are excluded. Stem cell collection during the first 9 cycles of protocol therapy is permitted * Grade 2 sensory or Grade 1 painful peripheral neuropathy
DRUG: Daratumumab, DRUG: Cyclophosphamide, DRUG: Bortezomib, DRUG: Dexamethasone
Amyloidosis
Seladelpar in Subjects With Primary Biliary Cholangitis (PBC) and Compensated Cirrhosis (AFFIRM)
Gilead Clinical Study Information Center - GileadClinicalTrials@gilead.com
PHASE3
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 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) ≥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 Talquetamab-related Oral Toxicity (Talisman)
Study Contact - Participate-In-This-Study1@its.jnj.com
PHASE2
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 talquetamab, 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 suggesting severe dysgeusia at screening. 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
Relapse Multiple Myeloma, Refractory Multiple Myeloma
A Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against B-cell Maturation Antigen (BCMA) in Participants With Multiple Myeloma (CARTITUDE-2)
Study Contact - Participate-In-This-Study1@its.jnj.com
PHASE2
NCT04133636
Inclusion Criteria:
* Cohort A: Received a minimum of 1 to a maximum of 3 prior lines of therapy including a proteasome inhibitor (PI) and immunomodulatory therapy (IMiD), and lenalidomide refractory per International Myeloma Working Group (IMWG) guidelines
* Cohort B: Received one line of prior therapy including a PI and an IMiD, and disease progression per IMWG criteria less than or equal to (\<=) 12 months after treatment with autologous stem cell transplantation (ASCT) or \<=12 months from the start of anti-myeloma therapy for participants who have not had an ASCT
* Cohort C: Previously treated with a PI, an IMiD, an anti-CD38 monoclonal antibody and B-cell maturation antigen (BCMA)-directed therapy
* Cohort D: Newly diagnosed multiple myeloma per IMWG with a history of 4 to 8 total cycles of initial therapy, including induction, high-dose therapy, and ASCT with or without consolidation
* Cohort E: Have newly diagnosed multiple myeloma without prior therapy (one cycle of prior therapy before enrollment is acceptable) and classified as high risk defined as either: 1) International Staging System (ISS) stage III criteria, Beta 2 microglobulin greater than or equal to (\>=) 5.5 milligrams per liter (mg/L) (via local or central laboratory assessment) or 2) high risk cytogenetic features del(17/17p), t (14;16), t(14;20), 1q amplification (at least 4 total copies) in at least 20 percent (%) of the total plasma cell population
* Cohort F:
* Participant must have a documented efficacy response of very good partial response (VGPR) or better, without progressive disease prior to enrollment, as assessed per IMWG 2016 criteria
* Received initial therapy as specified below. The dose/schedule of cycles administered will be as per standard of care. It is acceptable for up to 1 cycle of the protocol-specified regimens to be missing one of the listed agents (example, held due to toxicity). Acceptable combinations include: At least 5 to 8 cycles of initial therapy with daratumumab, bortezomib, lenalidomide and dexamethasone (D-VRd). The dose/schedule of cycles administered will be as per standard of care or; at least 4 to 8 cycles of initial therapy with daratumumab, lenalidomide and dexamethasone (D-Rd) or; at least 4 to 8 cycles of initial therapy with a carfilzomib-based triplet or quadruplet regimen
* Cohort G: Not considered for high-dose chemotherapy with autologous stem cell transplantation (ASCT) due to: a) Ineligibility due to advanced age; or b) Ineligibility due to presence of comorbid condition(s) likely to have a negative impact on tolerability of high-dose chemotherapy with ASCT; or c) Subject refusal of high-dose chemotherapy with ASCT as initial treatment
* Cohort H: Considered a candidate for high-dose chemotherapy with ASCT as initial treatment
* Cohorts A, B, C, E, G, H:
* Serum monoclonal paraprotein (M-protein) level greater than or equal to (\>=) 1.0 gram per deciliter (g/dL) or urine M-protein level \>=200 milligrams (mg)/24 hours
* Light chain multiple myeloma in whom only measurable disease is by serum free light chain (FLC) levels in the serum: Serum immunoglobulin FLC \>=10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio
* Cohort A: For participants with neither serum nor urine measurable disease, baseline positron emission tomography/ computed tomography (PET/CT) or whole -body magnetic resonance imaging (MRI) may be used to satisfy the measurable disease criteria. A minimum of one lesion with a bi-dimensional measurement of at least 1 centimeter (cm)\*1 cm is required
* Cohorts B, C: For participants with neither serum nor urine measurable disease, baseline positron emission tomography/ computed tomography (PET/CT) or whole body magnetic resonance imaging (MRI) may be used to satisfy the measurable disease criteria
* Cohorts A, B, C, D, E, F, G, H: Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1
Exclusion Criteria:
* Cohorts A, B, D, F: Any therapy that is targeted to BCMA
* Cohorts A, B, C, D, F: Prior treatment with chimeric antigen receptor T (CAR-T) therapy directed at any target
* Cohorts A, B, C, D, F:
* Ongoing toxicity from previous anticancer therapy must resolve to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy
* Received a cumulative dose of corticosteroids equivalent to \>=70 mg of prednisone within the 7 days (Cohort A, B, C, F) or 14 days (Cohort D) prior to apheresis
* Serious underlying medical condition, such as (a) evidence of active viral or bacterial infection requiring systemic antimicrobial therapy, or uncontrolled systemic fungal infection; (b) active autoimmune disease or a history of autoimmune disease within 3 years; (c) overt clinical evidence of dementia or altered mental status; (d) any history of Parkinson's disease or other neurodegenerative disorder
* Cohorts A, B, C, D, E, F: Known active, or prior history of central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma
* Cohorts F, G, and H: Active malignancies (that is, progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. The only allowed exceptions are: a) non-muscle invasive bladder cancer treated within the last 24 months that is considered completely cured; b) skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured; c) non-invasive cervical cancer treated within the last 24 months that is considered completely cured; d) localized prostate cancer (N0M0): with a Gleason score of greater than or equal to (=\>)6, treated within the last 24 months or untreated and under surveillance, with a Gleason score of 3+4 that has been treated more than 6 months prior to full study screening and considered to have a very low risk of recurrence, or history of localized prostate cancer and receiving androgen deprivation therapy and considered to have a very low risk of recurrence, e) breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ, or history of localized breast cancer and receiving antihormonal agents and considered to have a very low risk of recurrence; f) malignancy that is considered cured with minimal risk of recurrence
* Cohorts E, G, and H: Frailty index of \>= 2 according to Myeloma Geriatric Assessment score DRUG: JNJ-68284528, DRUG: Lenalidomide, DRUG: Daratumumab, DRUG: Bortezomib, DRUG: Dexamethasone
Multiple Myeloma
Cellular Therapy, CAR-T Therapy, BCMA CAR-T
Liver Cirrhosis Network Rosuvastatin Efficacy and Safety for Cirrhosis in the United States (LCN RESCU)
Crystal Santillanes, MS - lcn@northwestern.edu
PHASE2
NCT05832229
Inclusion Criteria:
• Age 18-75 years
• Cirrhosis due to nonalcoholic steatohepatitis, alcohol-associated liver disease, or chronic viral hepatitis (treated hepatitis B virus or hepatitis C virus)
• Clinical diagnosis of cirrhosis as defined investigator confirmation and the following:
• At least one liver biopsy within 5 years prior to consent showing either: Metavir stage 4 fibrosis; Ishak Stage 5-6 fibrosis, OR
• 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: vibration-controlled transient elastography within 48 weeks prior to consent or during Screening ≥15 kilopascal or magnetic resonance elastography within 48 weeks prior to consent or during Screening ≥5 kilopascal iii. Evidence of varices demonstrated on imaging or endoscopy within 3 years prior to consent or during Screening iv. Either: Fibrosis-4\>2.67 or platelets \<150/mL within 6 months prior to consent or during Screening
• Two measures of vibration-controlled transient elastography: one at screening and one at the randomization study visit, meeting the following criteria:
• The first measure must be ≥ 15 kilopascal.
• 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 kilopascal.
• 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) in patients of East Asian descent
• colchicine
• cyclosporin
• Additional medications that will be excluded: atazanavir/ritonavir capmatinib darolutamide dasabuvir/ombitasvir/paritaprevir/ritonavir ledipasvir/sofosbuvir elbasvir/grazoprevir erythromycin glecaprevir/pibrentasvir lopinavir/ritonavir regorafenib ritonavir, in any combination simeprevir sofbuvir/velpatasvir/voxilaprevir sofosbuvir/velpatasvir tafamidis 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:
• Unstable or active inflammatory bowel disease
• Active infection
• Any malignant disease (other than squamous or basal cell carcinoma of the skin) within previous 3 years
• Prior solid organ or hematopoietic cell transplant
• Bariatric surgery in the last 24 weeks prior to consent or planned bariatric surgery within the next 96 weeks
• 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:
• Hemoglobin \<10 g/dL
• Albumin \<3.0 g/dL
• Prolonged international normalized ratio (INR) \>1.5
• Total bilirubin ≥ 2.0 mg/dl (unless due to Gilbert's syndrome or hemolysis as denoted by normal direct bilirubin fraction)
• Direct bilirubin ≥ 0.9
• 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, or alkaline phosphatase (ALP) ≥ 300 within the past 24 weeks.
• 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.
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
NA
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
PHASE4
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
A Study Evaluating Atezolizumab, With or Without Bevacizumab, in Participants With Unresectable Hepatocellular Carcinoma and Child-Pugh B7 and B8 Cirrhosis (Kirros)
Reference Study ID Number: ML44719 https://forpatients.roche.com/ - global-roche-genentech-trials@gene.com
PHASE2
NCT06096779
General
Inclusion Criteria:
* Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology/cytology or clinically by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic participants
* Disease that is not amenable to curative surgical and/or locoregional therapies
* No prior systemic treatment (including systemic investigational agents) for locally advanced or metastatic and/or unresectable HCC
* Measurable disease (at least one untreated target lesion) according to RECIST v1.1
* ECOG Performance Status of 0-2 within 7 days prior to initiation of study treatment
* Child-Pugh B7 or B8 cirrhosis at screening and within 7 days prior to study treatment
* Adequate hematologic and end-organ function
* Life expectancy of at least 12 weeks
* Female participants of childbearing potential must be willing to avoid pregnancy and egg donation
* Absolute neutrophil count ≥1.0 x 109/L (≥1000/μL) without granulocyte colony-stimulating factor support
* Platelet count ≥ 50 × 109/L (50,000/μL) without transfusion
* Hemoglobin ≥ 80 g/L (8 g/dL) AST and ALT ≤ 5 × upper limit of normal (ULN)
* Serum bilirubin ≤ 3 × ULN
* Creatinine clearance ≥ 50 mL/min (calculated using the Cockcroft-Gault formula)
* Serum albumin ≥ 20 g/L (2.0 g/dL) without transfusion in the prior 3 months
* INR ≤2.3
General Exclusion Criteria:
* Pregnancy or breastfeeding
* Prior treatment with CD137 agonists or immune checkpoint blockade therapies
* Treatment with investigational therapy within 28 days prior to initiation of study treatment
* Treatment with locoregional therapy to liver within 28 days prior to initiation of study treatment, or non-recovery from side effects of any such procedure
* Treatment with systemic immunostimulatory agents
* Treatment with systemic immunosuppressive medication
* Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment
* Inadequately controlled hypertension
* Active or history of autoimmune disease or immune deficiency
* History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
* Participants who have a known concurrent malignancy that is progressing or requires active treatment, who have not completely recovered from treatment, or who have a significant malignancy history that, in the opinion of the investigator, should preclude participation.
* Participants on preventative hormonal therapies (i.e., tamoxifen and other hormonal inhibitors) are not excluded.
* Known fibrolamellar HCC, sarcomatoid HCC, other rare HCC variant, or mixed cholangiocarcinoma and HCC
* Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
* Prior allogeneic stem cell or solid organ transplantation
* Actively listed for liver transplantation
* Co-infection with hepatitis B virus (HBV) and hepatitis C virus (HCV)
* Untreated or incompletely treated esophageal and/or gastric varices with bleeding or that are at high risk for bleeding
* A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment
* Grade ≥3 hemorrhage or bleeding event within 6 months prior to initiation of study treatment
* Hepatic encephalopathy is allowed if no active symptoms or stable within 3 months of study treatment
* History, planned, or recommended placement of transjugular intrahepatic portosystemic shunt (TIPS) is excluded from Cohort A only. TIPS is acceptable in Cohort B.
* Diagnostic Paracentesis is allowed. Therapeutic Paracentesis within 3 months is an exclusion criteria
* Participants with ascites controlled on diuretics are allowed.
* History of spontaneous bacterial peritonitis within last 12 months DRUG: Atezolizumab, DRUG: Bevacizumab
Hepatocellular Carcinoma
Cirrhosis, liver cancer, liver tumor, Child-Pugh B, hepatocellular carcinoma, atezolizumab, bevacizumab, Immune Checkpoint Inhibitor, Digestive System Neoplasms, Kirros, ML44719, liver disease, Genentech, Immunotherapy, CPB, CPB 7, CPB 8, Tecentriq, Avastin, HCC, Cirrhotic Liver, Fatty Liver
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
PHASE3
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) between 18.0 and 39.0 kilograms per meter square (kg\^m2), inclusive.
* 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, 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 other forms of chronic liver 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 deciliter \[g/L\]).
* 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 Phase 1 Study With LYT-200 in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML), or With Relapsed/Refractory, High-risk Myelodysplastic Syndrome (MDS)
Chris Korth - clinicaltrials@puretechhealth.com
PHASE1
NCT05829226
Inclusion Criteria:
* Patients ≥ 18 years of age at the time of obtaining informed consent.
* Patients with morphologically documented primary or secondary AML by the World Health Organization(WHO) criteria, whose disease is relapsed/refractory to at least one line of prior therapy, with or without an allogeneic stem cell transplant and for whom no standard therapy that may provide clinical benefit is available or for patients who decline available standard of care.
* Patients with a documented diagnosis of high-risk myelodysplastic syndrome (MDS), whose disease is relapsed/refractory, post at least one line of treatment based on the revised International Prognostic Scoring System (IPSS-R) and for whom no standard therapy that may provide clinical benefit is available
* Patients are able and willing to comply with study procedures as per protocol, including bone marrowbiopsies.
* Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
* Patient must meet the following criteria as indicated on the clinical laboratory tests:
oWhite blood cell (WBC) count at the time of the first dose of \< 25,000/uL. oAspartate aminotransferase or alanine aminotransferase ≤ 3 × upper limit of normal (ULN; ≤ 5.0× ULN if considered to be due to leukemic involvement). oTotal bilirubin ≤ 2 × ULN (≤ 3 × ULN if considered to be due to leukemic involvement orGilbert's syndrome). oCreatinine clearance of ≥ 60 mL/min.
Exclusion Criteria:
* Patient diagnosed with acute promyelocytic leukemia (APL).
* Patient has active malignant tumors other than AML/MDS
* Patient has had HSCT and meets any of the following: has undergone HSCT within the 6- month period prior to the first study dose; has ≥ Grade 2 persistent non-hematological toxicity related to the transplant donor lymphocytes infusion.
* Patient has active graft versus host disease (GVHD) and patients receiving immunosuppressive treatment for GVHD.
* Patient with symptomatic central nervous system (CNS) involvement of leukemia or other CNS diseases related to underlying and secondary effects of malignancy
* Patient has had major surgery within 4 weeks prior to the first study dose.
* Patient has congestive heart failure New York Heart Association (NYHA) class 3 or 4, or patient with a history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multigated acquisition (MUGA) scan performed within 3 months prior to study entry results in a left ventricular ejection fraction (LVEF) that is ≥ 45%.
* Patient has any condition which, in the Investigator's opinion, makes the patient unsuitable for study participation. DRUG: LYT-200, DRUG: Venetoclax, DRUG: Azacitidine, DRUG: Decitabine
AML, Adult Recurrent, MDS
AML Recurrent, AML Relapsed, AML Refractory, Hematological Cancer, Gal-9, Immuno-oncology, MDS, MDS High Risk
A Study of Treatment for Medulloblastoma Using Sodium Thiosulfate to Reduce Hearing Loss
ctrrecruit@vcu.edu
PHASE3
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 Study Observing Everyday Effectiveness and Safety of the Drug Elafibranor in Participants With Primary Biliary Cholangitis Who Are Receiving Ongoing Treatment (ELFINITY)
Ipsen Clinical Study Enquiries - clinical.trials@ipsen.com
NCT06447168
Inclusion Criteria:
* Participant has provided written informed consent and agrees to comply with the study protocol.
* Participant with PBC diagnosis.
* Participant for whom the treating physician has decided to start or participants who are currently receiving treatment with commercialized elafibranor.
* If a participant has a caregiver who agrees to complete the caregiver questionnaires, an informed consent should be collected from the caregiver before any data is collected.
Exclusion Criteria:
* Participant is currently participating or, plans to participate in an investigational drug study or medical device study containing active substance.
* Participant with known hypersensitivity to the product or to any of its excipients.
* Participant with mental instability or incompetence, such that the validity of informed consent or ability to be compliant with the study is uncertain. Primary Biliary Cholangitis
A Long-Term Study of Elafibranor in Adult Participants With Primary Biliary Cholangitis (ELFIDENCE)
Ipsen Clinical Study Enquiries - clinical.trials@ipsen.com
PHASE3
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, with the exception of local, successfully treated basal cell carcinoma or in-situ carcinoma of the uterine cervix.
* 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 screening period: 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)
A Study to Evaluate the Efficacy, Safety, and Tolerability of BMS-986278 in Participants With Progressive Pulmonary Fibrosis
BMS Clinical Trials Contact Center www.BMSClinicalTrials.com - Clinical.Trials@bms.com
PHASE3
NCT06025578
Inclusion Criteria
* Diagnosis of interstitial lung disease (ILD) with features consistent with progressive ILD within 24 months prior to screening, and ≥ 10% extent of fibrosis on screening high-resolution computed tomography (HRCT).
* If on pirfenidone or nintedanib, participants must have been on a stable dose for at least 90 days prior to screening.
* If not currently on pirfenidone or nintedanib, participants must not have received either of these medications within 28 days prior to screening.
* Mycophenolate mofetil (MMF), mycophenolic acid (MA), azathioprine (AZA), and Tacrolimus are permitted provided that the participant is on a stable dose for at least 90 days prior to screening. If not currently on MMF, MA, AZA, or tacrolimus, participants must not have taken these medications within 28 days prior to screening.
* Traditional disease-modifying antirheumatic drug (DMARDs) (eg. Methotrexate, leflunomide, sulfasalazine, or hydroxychloroquine) are permitted provided that the participant is on a stable dose for at least 90 days prior to screening. If not currently on traditional DMARD, participants must not have taken these medications within 28 days prior to screening.
* Biologic DMARDs (eg. TNF blockers and IL-1 inhibitors) and Janus kinase inhibitors (JAK inhibitors eg. tofacitinib, upadacitinib) are permitted provided that the participant is on a stable dose for at least 90 days prior to screening. If not currently on Biologic DMARD or JAK inhibitor, participants must not have taken these medications within 28 days prior to screening.
* Women who are of childbearing potential must have a highly effective form of contraception and must provide a negative urine/serum pregnancy test.
* Men who are sexually active with women of childbearing potential agree to use male barrier contraception.
Exclusion Criteria
* Idiopathic pulmonary fibrosis with usual interstitial pneumonia (UIP) verification at screening.
* History of stroke or transient ischemic attack within 3 months prior to screening.
* Participants who exhibit symptoms of heart failure at rest.
* Participants who have a current malignancy; a previous malignancy with less than 2 years free of recurrence; and a biopsy that is suspicious for malignancy and the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory, or other diagnostic evaluations.
* Use of systemic corticosteroids equivalent to prednisone \> 15 mg/day is not allowed within 4 weeks prior to screening and during the study.
* Other protocol-defined Inclusion/Exclusion criteria apply.
DRUG: BMS-986278, DRUG: BMS-986278 Placebo
Progressive Pulmonary Fibrosis
BMS-986278, LPA1 antagonist, Pulmonary fibrosis, Interstitial lung disease, Rheumatoid Arthritis, Connective Tissue Disorders, Sarcoidosis, Scleroderma, Fibrosis, Antifibrotic therapy
A Study of Assessment on Safety and Effectiveness of BWI Pulsed Field Ablation With OMNYPULSE Catheter for the Treatment of Paroxysmal Atrial Fibrillation (PAF) (OMNY-AF)
Study Contact - rshar120@its.jnj.com
NA
NCT06455098
Inclusion Criteria:
* Diagnosed with symptomatic paroxysmal AF with:
• At least two symptomatic AF episodes within last six months from enrollment
• At least one electrocardiographically documented AF episode within twelve months prior to enrollment * Failed at least one Class I or Class III antiarrhythmic drug * Willing and capable to provide consent * Able and willing to comply with all pre-, post- and follow-up testing and requirements
Exclusion Criteria:
* Previously diagnosed with persistent AF (greater than \[\>\] 7 days in duration)
* AF secondary to electrolyte imbalance, thyroid disease, or reversible or non-cardiac cause.
* Previous surgical or catheter ablation for AF
* Patients known to require ablation outside the PV ostia and outside the CTI region.
* Documented severe dilatation of the left atrium (LAD\>50 mm) antero-posterior diameter on imaging within 6 months prior to enrollment
* Documented left atrium (LA) thrombus by imaging within 48 hours of the procedure
* Documented severely compromised left ventricular ejection fraction (LVEF \<40%) by imaging within 6 months prior to enrollment
* Uncontrolled heart failure or New York Heart Association (NYHA) Class III or IV
* History of blood clotting, bleeding abnormalities or contraindication to anticoagulation (heparin, warfarin, or dabigatran)
* Documented thromboembolic event (including transient ischemic attack or TIA) within the past 6 months
* Previous Percutaneous Coronary Intervention (PCI)/ myocardial infarction \[MI\] within the past 2 months
* Coronary Artery Bypass Grafting (CABG) surgery within the past 6 months
* Valvular cardiac surgical/percutaneous procedure
* Unstable angina within 6 months
* Anticipated cardiac transplantation, cardiac surgery, or other major surgery within the next 12 months
* Significant pulmonary disease or any other disease or malfunction of the lungs or respiratory system that produces severe chronic symptoms
* Significant congenital anomaly or medical problem that in the opinion of the investigator would preclude enrollment in this study
* Prior diagnosis of pulmonary vein stenosis
* Pre-existing hemi diaphragmatic paralysis
* Acute illness, active systemic infection, or sepsis
* Presence of intracardiac thrombus, myxoma, tumor, interatrial baffle or patch or other abnormality that precludes catheter introduction or manipulation
* Severe mitral regurgitation
* Presence of an implanted pacemaker or Implantable Cardioverter-Defibrillator (ICD) or other implanted metal cardiac device (other than coronary stents) that may interfere with the PF energy field)
* Presence of a condition that precludes vascular access
* Current enrollment in an investigational study evaluating another device or drug
* Women who are pregnant (as evidenced by pregnancy test if pre-menopausal), lactating, or who are of child-bearing age and plan on becoming pregnant during the course of the clinical investigation
* Life expectancy less than 12 months
* Presenting contra-indications for the devices used in the study, as indicated in the respective Instructions for Use (IFU) DEVICE: OMNYPULSE™ Catheter with the TRUPULSE Generator
Atrial Fibrillation
Testing the Addition of an Immunotherapy Drug, Cemiplimab (REGN2810), Plus Surgery to the Usual Surgery Alone for Treating Advanced Skin Cancer
ctrrecruit@vcu.edu
PHASE3
NCT06568172
Inclusion Criteria:
* Pathologically (histologically or cytologically) proven diagnosis of invasive cutaneous squamous cell carcinoma (CSCC) or regional lymph node or in-transit metastasis of CSCC
* For patients with regional metastasis without a primary tumor at screening: a clinical history of CSCC that drains to the involved regional lymph nodes or in-transit metastases in question is required
* For example, a parotid mass shown to be squamous cell carcinoma (SCC) by cytologic analysis of a fine needle aspirate in a patient with a clinical history of CSCC on the ipsilateral scalp would be eligible
* For patients with regional metastases without a primary tumor and an ambiguous clinical history: tumor genomic sequencing suggesting a primary tumor of cutaneous origin would be acceptable evidence to establish eligibility
* NOTE: Tumor genomic sequencing is not required to determine eligibility, but may be part of the routine evaluation of patients with cancers of unknown primary at some institutions. For example, a parotid mass shown to be SCC by cytologic analysis of fine needle aspirate without a primary tumor and an ambiguous clinical history, but with a tumor genomic sequencing assay demonstrating a high tumor mutation burden (≥ 10 mutations/Mb) and/or a high fraction of ultraviolet (UV) related mutations (\> 50% of mutations \[cytosine (C)/thymine (T)\]C \> T or CC \> TT) and/or the presence of "signature 7" mutations would be eligible (Chang 2021)
* Previously untreated or recurrent CSCC
* Clinical American Joint Committee on Cancer (AJCC) 8th Edition (head and neck sites) or Union for International Cancer Control (UICC) (non-head and neck sites) stage III or IV
* Primary tumor site must be in the head and neck cutaneous region, other non-head and neck cutaneous regions, or eyelid cutaneous region
* No mucosal squamous cell carcinoma (vermillion lip, nasal, oral, sinonasal, conjunctival, anogenital)
* Tumor must be resectable with curative intent. Note: Tumor with bony skull base invasion and/or skull base foramen involvement (T4b) is not eligible
* At least 1 lesion that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
* No definitive clinical or radiologic evidence of distant metastatic disease (M1), visceral and/or distant nodal disease
* Age ≥ 18
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
* Not pregnant and not nursing
* Negative urine or serum pregnancy test (in persons of childbearing potential) within 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal
* Absolute neutrophil count (ANC) ≥ 1,000 cells/mm\^3
* Platelets ≥ 75,000 cells/mm\^3
* Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin \[Hgb\] ≥ 8.0 g/dl is acceptable)
* Creatinine clearance (CrCL) \> 30mL/min by the Cockcroft-Gault formula
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (NOTE: For patients with Gilbert's syndrome, total bilirubin ≤ 3 x ULN. Gilbert's syndrome must be documented appropriately as past medical history.)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) ≤ 3 x institutional ULN
* No prior systemic therapy for the study cancer
* No prior radiotherapy to the region of the study cancer that would result in cumulative doses of radiation to organs at risk for radiation injury that exceed protocol limitations
* No history of myocardial infarction within the last 6 months
* New York Heart Association functional classification IIb or better (New York Heart Association \[NYHA\] functional classification III/IV are not eligible) (Note: 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)
* No active infection requiring systemic antibiotics, antiviral, or antifungal treatments
* No history of allogeneic stem cell transplantation, or autologous stem cell transplantation
* No history of a solid organ transplant (other than corneal transplant)
* No active, known, or suspected autoimmune disease
* Active or known disease is defined as:
* Requiring higher than physiologic steroid levels (\> 10mg prednisone/day or equivalent) or
* Requiring disease-modifying agents or
* Ongoing or recent (within 5 years prior to registration) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-related adverse events (irAEs)
* NOTES:
* Patients meeting the following criteria are not considered immunosuppressed and are eligible to enroll:
* Patients who require a brief course of steroids (eg, prophylaxis for imaging assessments due to hypersensitivity to contrast agents) are not excluded
* Patients with type I diabetes mellitus, and endocrinopathies (including hypothyroidism due to autoimmune thyroiditis) only requiring hormone replacement, or skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
* Physiologic replacement doses ≤ 10 mg prednisone/day or equivalent allowed, as long as they are not being administered for immunosuppressive intent. Inhaled or topical steroids are permitted
* Patients with the following immunosuppressed conditions are eligible to enroll:
* Patients with HIV infection on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible
* Patients with chronic lymphocytic leukemia (CLL) with no history of anti-CLL therapy within 6 months prior to registration are eligible
* No history of interstitial lung disease (eg, idiopathic pulmonary fibrosis, organizing pneumonia)
* No active, noninfectious pneumonitis requiring immune-suppressive therapy
* No active tuberculosis
* No live vaccines within 28 days prior to registration
* No history of allergic reaction to the study agent, compounds of similar chemical or biologic composition to the study agent (or any of its excipients) PROCEDURE: Biospecimen Collection, BIOLOGICAL: Cemiplimab, PROCEDURE: Computed Tomography, RADIATION: Image Guided Radiation Therapy, RADIATION: Intensity-Modulated Radiation Therapy, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Positron Emission Tomography, OTHER: Questionnaire Administration, PROCEDURE: Surgical Procedure, PROCEDURE: Surgical Procedure
Recurrent Head and Neck Cutaneous Squamous Cell Carcinoma, Recurrent Skin Squamous Cell Carcinoma, Resectable Head and Neck Cutaneous Squamous Cell Carcinoma, Resectable Skin Squamous Cell Carcinoma, Stage III Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8, Stage IV Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8
A Study to Evaluate Vimseltinib in Adults With Active Chronic Graft-Versus-Host Disease (cGVHD)
Clinical Team - clinicaltrials@deciphera.com
PHASE2
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 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.
• 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
A Trial of Felzartamab in Kidney Transplant Recipients With Late Antibody-Mediated Rejection (AMR) (TRANSCEND)
US Biogen Clinical Trial Center - clinicaltrials@biogen.com
PHASE3
NCT06685757
Key
• Intravenous or subcutaneous immunoglobulin (IVIg or subcutaneous immunoglobulin \[SCIg\]) or PLEX.
• Complement system inhibitors (e.g., eculizumab).
• Proteasome inhibitors (e.g., bortezomib).
• Tocilizumab. e. Any other investigational agent within 3 months or 5 half-lives (whichever is longer) of randomization. Other protocol-defined inclusion/exclusion criteria apply.
Inclusion Criteria:
* Active or chronic active AMR (biopsy-confirmed) without TCMR per central reading, as defined by the Banff 2022 criteria.
* Kidney transplant at least 6 months prior to Screening visit (recipients of either living or deceased donors).
* Donor-specific antibody (DSA): Human leukocyte antigen (HLA) Class I and/or II antigen-specific DSA-positive (preformed and/or de novo DSA) as determined by the local laboratory's definition of positivity using singleantigen bead-based assays within 3 months prior to randomization.
Key Exclusion Criteria:
* Transplant: Blood type (ABO)-incompatible transplant.
* History of multiple organ transplants including en bloc and dual kidney transplants.
* Acute, rapid decline in renal function, defined as a participant likely to require renal replacement therapy within the subsequent 30 days as determined by the Investigator.
* Treatment: Prior AMR/TCMR treatment (with the exception of corticosteroids) within 3 months prior to randomization is excluded as listed below. Participants who received any of these treatments between 3 and 6 months prior to randomization must have both a renal biopsy (IC3) and DSA testing at least 6 weeks after completing (or stopping) treatment in order to confirm continuing AMR and to determine eligibility:
• Intravenous or subcutaneous immunoglobulin (IVIg or subcutaneous immunoglobulin \[SCIg\]) or PLEX.
• Complement system inhibitors (e.g., eculizumab).
• Proteasome inhibitors (e.g., bortezomib).
• Tocilizumab. e. Any other investigational agent within 3 months or 5 half-lives (whichever is longer) of randomization. Other protocol-defined inclusion/exclusion criteria apply.
DRUG: Felzartamab, DRUG: Placebo
Antibody-mediated Rejection
AMR, Felzartamab, Kidney Transplant
Zanubrutinib in Patients With DLBCL and MYD88 or NOTCH1 Mutation or CD5+
Massey IIT Research Operations - masseyepd@vcu.edu
PHASE2
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 (MYC) and BCL-2 and/or BCL6 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
NA
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;
* Treatment with IV diuretics (does not have to be continuous) for ≥21 days during the current hospitalization (including time spent at an outside hospital);
* 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;
* Known amyloidosis of any type;
* 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 intra-aortic balloon pump (IABP) within the last 14 days or use of an extracorporeal membrane oxygenation (ECMO) or percutaneous ventricular assist device (e.g., Impella or TandemHeart) within the last 30 days. * Known amyloidosis of any type. * 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 intra-aortic balloon pump (IABP) within the last 14 days or use of an extracorporeal membrane oxygenation (ECMO) or percutaneous ventricular assist device (e.g., Impella or TandemHeart) within the last 30 days. * Known amyloidosis of any type. * 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
ML-004 in Adolescents and Adults With Autism Spectrum Disorders (ASD)
Clinical Trials Contact Center - ML-004-002@Maplightrx.com
PHASE2
NCT05081245
Inclusion Criteria:
* Age 12 to 45 at screening
* Has a designated care/study partner who can reliably report on symptoms
* Has a diagnosis of Autism Spectrum Disorder (ASD)
* Has a body mass index (BMI) 18 through 34 kg/m², inclusive
* Full scale IQ (or equivalent) ≥55 score, with adequate verbal fluency, as determined by the Principal Investigator.
* Psychoactive medications and adjunctive therapies are stable for 4 weeks prior to screening
* Must be able to swallow study medication
Exclusion Criteria:
* Has Rett syndrome or Child Disintegrative Disorder
* Has participated in any other study and received any other investigational medication (other than COVID-19 vaccination) or device within 60 days prior to screening
* History of epilepsy without current adequate control, or any seizure in the 6 months preceding screening
* History of suicidal ideation or behavior in the past 12 months, or a positive response to C-SSRS questions 4 and/or 5
* Systolic blood pressure ≥140 mmHg (if adult) or \>135 mmHg (if adolescent), or diastolic blood pressure ≥90 (if adult) or \>85 mmHg (if adolescent), or a clinical history of uncontrolled or severe hypertension
* If female, is pregnant or lactating DRUG: ML-004 (IR)/(ER) tablet, DRUG: ML-004 Placebo
Autism Spectrum Disorder
ASD, Autism, Autism Spectrum Disorder, Social Communication
A Phase 2 Study of PTX 100 in Patients With Relapsed/Refractory CTCL
Upaly Bahadure - upaly@ptxtherapeutics.com
PHASE2
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.
• Active viral, bacterial, fungal infection or other serious infection requiring ongoing systemic treatment. Routine antimicrobial prophylaxis is permitted.
• 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.
• On an immunomodulatory drug for concomitant or intercurrent conditions or who have received any of these agents within 4 weeks of baseline.
• 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.
• 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.
• Prior allogeneic or autologous hematopoietic transplantation 11. Has a known psychiatric disorder that would interfere with compliance with the requirements of the study.
• 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