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A Study of Amivantamab and mFOLFOX6 or FOLFIRI Versus Cetuximab and mFOLFOX6 or FOLFIRI as First-line Treatment in Participants With KRAS/NRAS and BRAF Wild-type Unresectable or Metastatic Left-sided Colorectal Cancer (OrigAMI-2)
Study Contact - Participate-In-This-Study1@its.jnj.com
NCT06662786
Inclusion Criteria:
* Have histologically or cytologically confirmed adenocarcinoma of the left-sided colorectal cancer. Participants must have unresectable or metastatic disease
* Determined to have Kirsten rat sarcoma viral oncogene (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), and v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type (WT) tumor by local and/or central testing (if available)
* Must agree to the submission of fresh tumor tissue
* Have measurable disease according to RECIST v1.1
* Has not received any prior systemic therapy for unresectable or metastatic colorectal cancer (CRC). Prior adjuvant/neoadjuvant therapy in the non-metastatic disease is permitted. However, the last course of adjuvant or neoadjuvant chemotherapy must have concluded greater than (\>) 12 months prior to CRC recurrence/metastases
* Have an eastern cooperative oncology group (ECOG) performance status (PS) of 0 or 1
Exclusion Criteria:
* Has medical history of (noninfectious) interstitial lung disease (ILD) /pneumonitis/pulmonary fibrosis or has current ILD/pneumonitis/pulmonary fibrosis, or where suspected ILD/pneumonitis/pulmonary fibrosis cannot be ruled out by imaging at screening
* Has known allergies, hypersensitivity, or intolerance to excipients of any of the following: (a) amivantamab or cetuximab, (b) any component of mFOLFOX6 and, (c) any component of FOLFIRI
* Has a prior or concurrent second malignancy other than the disease under study or one whose natural history or treatment is likely to interfere with any study endpoints of safety or the efficacy of the study treatment(s)
* Participant with known mismatch repair deficiency (dMMR)/ high microsatellite instability (MSI-H) status and human epidermal growth factor receptor 2 (HER2)-positive/amplified tumor
* Has prior exposure to any agents that target epidermal growth factor receptor (EGFR), mesenchymal epithelial transition (MET) or vascular endothelial growth factor (VEGF) BIOLOGICAL: Amivantamab, BIOLOGICAL: Cetuximab, DRUG: 5-fluorouracil, DRUG: Leucovorin calcium/Levoleucovorin, DRUG: Oxaliplatin, DRUG: Irinotecan Hydrochloride
Colorectal Neoplasms
Olutasidenib Single Plus Combo Therapy in IDH1mut AML After Induction and Consolidation
Massey IIT Research Operations - masseyepd@vcu.edu
NCT07130695
Inclusion Criteria:
* Histologically or cytologically confirmed non-acute promyelocytic isocitrate dehydrogenase (1 IDH1) mutant acute myeloid leukemia (AML). IDH1 mutation may be identified by NGS or PCR based methods and identified at time of diagnosis or any other time point prior to enrollment.
* Completed induction and/or consolidation intended as per treating physician to reach complete response (CR),complete response with partial hematologic recovery (CRh), or complete response with incomplete hematologic recovery (CRi), or morphologic leukemia free state (MLFS) at time of study enrollment Patients must be within 90 days of their last cycle of upfront therapy.
* Age ≥18 years
* Calculated creatinine clearance (by Cockroft-Gault) ≥30 mL/min
* Total bilirubin ≤2 × upper limit of normal (ULN) Note: patients with Gilbert's syndrome may be included if total bilirubin is ≤3 × ULN and direct bilirubin is ≤2 × ULN
* Serum aspartate aminotransferase/ alanine aminotransferase (AST/ALT) ≤3 × ULN
* Eastern Cooperative Oncology Group (ECOG) 0, 1, or 2 or KPS \>50%
* Able to take oral medications
* Women of childbearing potential must consent to effective contraception during study treatment and at least 6 months following the last dose. Effective methods of contraception include oral or injectable hormonal birth control, intrauterine device (IUD), and double- barrier methods. (ie, combination of male condom with either cap, diaphragm or sponge with spermicide)
* Male participants who are sexually active with a woman of childbearing potential and who have not had vasectomies must be willing to use a barrier method of contraception and refrain from sperm donation from initial study drug until 90 days after last dose of study drug.
Exclusion Criteria:
* History of hypersensitivity or allergic reaction to olutasidenib or its components
* Corrected Q-T interval (QTc) (Fredericia calculation) \> 450 ms (after corrective action is taken)
* History of Torsades de Pointes
* Any gastrointestinal condition thought by the treating investigator to impair oral absorption of medication
* Stem cell transplant eligible and planned within 60 days of study start date in the opinion of the treating investigator
* Uncontrolled intercurrent illness or infection (those with controlled human immunodeficiency virus (HIV), hepatitis, or other chronic infections are eligible)
* Female participants who are pregnant or intend to donate eggs during the study or for 6 months after receiving their last dose of study drug
* Nursing women, women of childbearing potential with positive pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception. (Appropriate method(s) of contraception include oral or injectable hormonal birth control, IUD, and double-barrier methods)
* Male participants who intend to donate sperm during the course of this study or for 3 months after last dose
* Participants receiving, or are expected to require during the study, any concomitant medications that may interfere with efficacy, metabolism, or safety of the investigational agent, including drugs known to cause QT prolongation. for which drug interactions with olutasidenib would be prohibitory
* Concurrent chemotherapy for non-AML malignancy that is expected to interfere with the efficacy, metabolism, or safety of the agent under investigation
* Received non-intensive upfront therapy including hypomethylating agents (HMA) /Venetoclax based
* Currently receiving other targeted therapies or AML directed therapies, including but not limited to other IDH1 or IDH2 inhibitors, FMS-like tyrosine kinase 3 (FLT3) inhibitors, B-cell lymphoma 2 (BCL-2) inhibitors, menin inhibitors
* Other investigational agents in another clinical trial within 4 weeks prior to enrollment
* Systemic corticosteroids above physiologic replacement doses (10mg/day prednisone or equivalent), unless used to tread IDH differentiation syndrome or as part of a pre-specified protocol exception
* Medical, psychological, or social condition that, in the opinion of the investigator, may increase the participant's risk or limit the participant's adherence with study requirements DRUG: Olutasidenib Investigational Agent Administration
Acute Myeloid Leukemia
Acute Myeloid Leukemia
A Study Using Risk Factors to Determine Treatment for Children With Favorable Histology Wilms Tumors (FHWT)
ctrrecruit@vcu.edu
NCT06401330
Inclusion Criteria:
* Patients must be enrolled on APEC14B1 and consent to Part A - Eligibility Screening prior to enrollment on AREN2231.
* Patients must be \< 30 years old at enrollment.
* Patients with newly diagnosed Stage I-IV Favorable Histology Wilms Tumor confirmed by central review and with a qualifying Initial Stratum Assignment on APEC14B1.
* Patients must receive a qualifying Initial Stratum Assignment on APEC14B1-REN by Day 14 post-diagnostic procedure (nephrectomy or biopsy), where that procedure is Day 0.
* Patients must enroll on AREN2231 by Day 14.
* Exceptions: If patient reaches Day 14 (post initial diagnostic nephrectomy or biopsy) without receiving an Initial Stratum Assignment on APEC14B1-REN, patient will not be eligible for enrollment on AREN2231 unless all required materials (reports and Case Report Forms and specimens) for an Initial Stratum Assignment arrived by Day 7, but an Initial Stratum Assignment was not completed by Day 14. In these circumstances, after obtaining appropriate protocol consent, the patient may proceed with treatment according to local institutional staging and enroll within 5 calendar days of notification of the central Initial Stratum Assignment being issued, only if the AREN2231 Initial Stratum Assignment is in agreement with any treatment already initiated. If the Initial Stratum Assignment is not in agreement with the local institution's assessment then the patient will be ineligible for AREN2231.
* All sites must have sent or plan to send diagnostic tumor sample for molecular testing through a Clinical Laboratory Improvement Act (CLIA)-certified (or equivalent if outside of the United States \[US\]) laboratory that can detect Loss of Heterozygosity (LOH) of chromosome 1p AND 16q, and gain of chromosome 1q. Patients potentially eligible for mVLR must also have LOH of chromosome 11p15 included.
* Note: Patients are eligible for enrollment prior to obtaining these molecular testing results, and it is strongly recommended that patients are enrolled before these results are available. However, molecular results must be returned and uploaded to APEC14B1-REN for integration into risk stratification by the required timepoints (specific timelines vary by treatment arm). Patients who do not have molecular results available by the arm-specific timepoints may be taken off protocol therapy.
* Patients who have an upfront nephrectomy must have at least one lymph node sampled and confirmed as a lymph node by central pathology review to be eligible.
* Note: Lymph node sampling will also be required at delayed nephrectomy. Patients who do not have a lymph node sampled and confirmed as a lymph node by central pathology review at delayed nephrectomy will be taken off protocol therapy.
* Karnofsky performance status must be ≥ 50 for patients \> 16 years of age and the Lansky performance status must be ≥ 50 for patients ≤ 16 years of age.
* ONLY TO PATIENTS WHO WILL RECEIVE CHEMOTHERAPY: Serum total bilirubin ≤ 1.5 X upper limit of normal (ULN) OR direct bilirubin ≤ 3X ULN for subjects with total bilirubin levels \> 1.5 ULN (within 7 days prior to enrollment).
* ONLY TO PATIENTS WHO WILL RECEIVE CHEMOTHERAPY: Aspartate aminotransferase (AST/serum glutamate oxaloacetic transaminase \[SGOT\]) OR alanine transaminase (ALT/serum glutamic pyruvate transaminase \[SGPT\]) ≤ 3X ULN OR ≤ 5 X ULN for patients with liver metastases (within 7 days prior to enrollment).
* ONLY TO PATIENTS WHO WILL RECEIVE CHEMOTHERAPY: Shortening fraction of ≥ 27% by echocardiogram, or ejection fraction of ≥ 50% (within 7 days prior to enrollment)
* Note: This criteria only applies to patients centrally classified as Stage IV. Stage II and III patients subsequently assigned to a doxorubicin arm will be off protocol therapy if they do not meet this criteria at time of cardiac function assessment.
* Known HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
* 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:
* Patient with a diagnosis of Stage V Bilateral Wilms Tumor.
* Patients who in the opinion of the investigator are not able to comply with the study procedures are not eligible.
* Patients with any uncontrolled, intercurrent illness including but not limited to symptomatic congestive heart failure.
* Patients with Stage I FHWT with a known or suspected Wilms Tumor predisposition syndrome or condition (contralateral nephrogenic rests and/or unilateral multicentric tumors) are excluded from treatment on the mVLR (Nephrectomy Only) arm.
* Notes:
* In the context of the renal tumor protocols, multicentric tumors and multifocal tumors are equivalent terms, and refer to the occurrence of two or more tumors arising within one kidney.
* Exclusion from the Nephrectomy Only arm applies to two groups of patients:
* Patients \< 4 years with Stage I FHWT other than epithelial subtype AND
* Stage I patients of any age with Epithelial WT
* For the purpose of exclusion from the Nephrectomy Only Arm, known or suspected WT predisposition syndromes or conditions are defined as follows:
* WT Predisposition Syndromes: Beckwith Wiedemann Spectrum, Denys Drash, Trisomy 18, Idiopathic Hemihypertrophy/Isolated Lateralized Overgrowth, WAGR, Simpson-Golabi-Behmel, Bohring-Opitz, or other conditions considered by treating physician to predispose to WT.
* WT Predisposing Conditions:
* A unilateral WT and (radiologic or pathologic) determination of contralateral nephrogenic rest(s) AND/OR
* Unilateral multicentric WT
* Patients treated with partial nephrectomy at initial diagnosis are excluded from mVLR (Nephrectomy Only) arm.
* Patients with lung metastases as the only metastatic site who already had complete resection of all radiologically evident lung nodules, and have at least one nodule confirmed pathologically as tumor.
* Please note: Those with lung metastases as the only metastatic site who have complete resection of all radiologically evident lung nodules after enrollment but prior to the lung imaging following Cycle 2 of DD-4A will be inevaluable for lung assessment and subsequent stratum assignment and will, therefore, come off protocol therapy.
* Patients with known Charcot-Marie-Tooth syndrome.
* Patients who have had prior tumor-directed chemotherapy or radiotherapy for the current diagnosis except for therapy delivered for an emergent issue, as medically indicated.
* Patients who will potentially require doxorubicin on this study and have previously received doxorubicin for another diagnosis.
* Patients receiving concurrent chemotherapy for a different diagnosis.
* 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: Bone Scan, DRUG: Carboplatin, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, BIOLOGICAL: Dactinomycin, DRUG: Doxorubicin, DRUG: Etoposide, DRUG: Irinotecan, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Nephrectomy, OTHER: Patient Observation, PROCEDURE: Positron Emission Tomography, PROCEDURE: Ultrasound Imaging, DRUG: Vincristine, PROCEDURE: X-Ray Imaging
Stage I Mixed Cell Type Kidney Wilms Tumor, Stage II Mixed Cell Type Kidney Wilms Tumor, Stage III Mixed Cell Type Kidney Wilms Tumor, Stage IV Mixed Cell Type Kidney Wilms Tumor
Testing the Use of Ado-Trastuzumab Emtansine Compared to the Usual Treatment (Chemotherapy With Docetaxel Plus Trastuzumab) or Trastuzumab Deruxtecan for Recurrent, Metastatic, or Unresectable HER2-Expressing Salivary Gland Cancers
ctrrecruit@vcu.edu
NCT05408845
Inclusion Criteria:
* Pathologically (histologically or cytologically) proven diagnosis of HER2-positive OR HER2-low expressing recurrent/metastatic salivary gland cancer (SGC)
* HER2-positive cohort:
* Note: The majority of HER2-positive SGCs are salivary duct carcinoma (SDCs), but to a lesser extent, other SGC subtypes can be HER2-positive (e.g., adenocarcinomas, mucoepidermoid carcinomas, etc.) and are eligible to be included on the study. Additionally, pathologists may sign out SDCs under other descriptors (e.g., ex-pleomorphic adenoma, adenocarcinoma), and these would be eligible if they are HER2-positive.
* Note: HER2 evaluation based on local site immunohistochemistry (IHC), fluorescent in-situ hybridization (FISH), or local/commercial next-generation sequencing (NGS) is required. Any one of the following criteria observed in a primary tumor or metastasis would meet the study definition for "HER2-positive":
* Immunohistochemistry (IHC) (3+) per the College of American Pathologists (CAP) breast cancer guidelines
* Gene amplification by FISH (HER2/CEP17 ratio \>= 2.0)
* Gene amplification by NGS (fold change \>= 2)
* HER2-low expressing cohort:
* Note: Local HER2 evaluation by immunohistochemistry (IHC) or fluorescent in-situ hybridization (FISH) is required. Any one of the following criteria observed in a primary tumor or metastasis would meet the study definition for "HER2-low":
* IHC 1+ per the College of American Pathologists (CAP) breast cancer guidelines
* IHC 2+ without evidence of amplification by FISH
* Patients with unresectable disease who are not candidates for curative surgery or radiation OR recurrent OR metastatic disease that is evident on radiologic imaging
* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy
* HER2-positive cohort: Measurable or non-measurable disease by the RECIST v1.1 criteria. HER2-low expressing cohort: Measurable disease by the RECIST v1.1 criteria
* History/physical examination within 30 days prior to registration
* The following imaging within 60 days prior to registration:
* CT or MRI of the neck (diagnostic quality with contrast, unless contraindicated) AND
* CT scan of the chest (diagnostic quality with contrast, unless contraindicated) AND
* If clinically indicated, CT or MRI of the abdomen and pelvis (diagnostic quality with contrast, unless contraindicated)
* Age \>= 18
* Left ventricular ejection fraction (LVEF) \>= 50% assessed by echocardiogram or multigated acquisition (MUGA) scan within 30 days prior to registration
* Zubrod (Eastern Cooperative Oncology Group \[ECOG\]) Performance Status of 0-2 within 14 days prior to registration
* Absolute neutrophil count (ANC) \>= 1,500 cells/mm\^3 (within 14 days prior to registration)
* Platelets \>= 100,000 cells/mm\^3 (within 14 days prior to registration)
* Hemoglobin \>= 9.0 g/dL (within 14 days prior to registration)
* HER2-positive cohort: Note: The use of transfusion or other intervention to achieve hemoglobin \[Hgb\] \>= 9.0 g/dL is acceptable
* HER2-low expressing cohort: Note: Transfusion (red blood cell or platelet) or granulocyte-colony stimulating factor (granulocyte colony-stimulating factor \[G-CSF\]) is not allowed
* Serum creatinine =\< 1.5 x upper limit of normal (ULN) OR calculated creatinine clearance (CrCl) \>= 30 mL/min by the Cockcroft-Gault formula (within 14 days prior to registration)
* HER2-positive cohort: Total bilirubin =\< 1.5 x ULN (within 14 days prior to registration) (Not applicable to patients with known Gilbert's syndrome) (within 14 days prior to registration)
* HER2-positive cohort: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 1.5 x ULN (within 14 days prior to registration)
* HER2-low expressing cohort: Total bilirubin ≤ 1.5 x ULN if no liver metastases; or \< 3 x ULN in the presence of documented Gilbert's Syndrome or liver metastases (within 14 days prior to registration) (within 14 days prior to registration)
* HER2-low expressing cohort: AST and ALT ≤ 3 x ULN if no liver metastases; or \< 5 x ULN with liver metastases (within 14 days prior to registration)
* HER2-low expressing cohort: Serum albumin ≥ 2.5 g/dL (within 14 days prior to registration)
* Known human immunodeficiency virus (HIV) infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial. Testing is not required for entry into protocol
* For patients with known evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Note: Known positive test for hepatitis B virus surface antigen (HBV sAg) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy. Patients who are immune to hepatitis B (anti-hepatitis B surface antibody positive) are eligible (e.g., patients immunized against hepatitis B)
* For patients with a known history of hepatitis C virus (HCV) infection, they 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
* Note: Known positive test for hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy
* 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
* Willing to use highly effective contraceptives for participants of childbearing potential (participants who may become pregnant or who may impregnate a partner) during therapy and for 7 months following last dose of study drug; this inclusion is necessary because the treatment in this study may be significantly teratogenic. Women must refrain from donating eggs during this same period
* Men with partners of childbearing potential must be willing to use a highly effective form of non-hormonal contraception or two effective forms of non-hormonal contraception by the patient and/or partner, and to continue the use of contraception for the duration of study treatment and for at least 7 months after the last dose of study treatment. Male patients whose partners are pregnant should use condoms for the duration of the pregnancy. Men must refrain from donating sperm during this same period
* Prior to registration, patients who have had chemotherapy or palliative-intent radiotherapy must have all toxicities related to prior treatment recovered to ≤ grade 1
* 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
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
Exclusion Criteria:
* HER2-positive cohort: Prior systemic therapy for the study cancer in the unresectable or recurrent and/or metastatic disease setting
* Note: Prior chemotherapy for a different cancer is allowed; prior androgen receptor targeted therapy in any setting is allowed; prior systemic therapy, including HER2-directed therapies given as neoadjuvant therapy, adjuvant therapy, and/or concurrently with radiation is allowed
* HER2-low expressing cohort: HER2 directed therapy for unresectable or recurrent or metastatic disease is not allowed
* Severe, active co-morbidity defined as follows:
* Unstable angina requiring hospitalization in the last 6 months
* Myocardial infarction within the last 6 months
* New York Heart Association Functional Classification III/IV (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.)
* Persistent grade 3-4 (CTCAE version 5.0) electrolyte abnormalities that cannot be reversed despite replacement as indicated by repeat testing
* Patient must not have an active infection requiring IV antibiotics, antivirals, or antifungals
* HER2-positive cohort only: \>= grade 3 peripheral neuropathy
* Interstitial lung disease or pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on chest CT scan
* Any hemorrhage or bleeding event grade \>= 3 within 28 days prior to registration
* History of allergic reactions to compounds of similar chemical or biologic composition to: HER2-positive cohort: ado-trastuzumab emtansine, trastuzumab, and/or docetaxel (or any of their excipients). HER2-low expressing cohort: DS-8201a (trastuzumab deruxtecan), trastuzumab
* History of exposure to the following cumulative doses of anthracyclines:
* Doxorubicin or liposomal doxorubicin \> 500 mg/m\^2
* Epirubicin \> 900 mg/m\^2
* Mitoxantrone \> 120 mg/m\^2
* Note: If another anthracycline, or more than one anthracycline has been used, the cumulative dose must not exceed the equivalent of doxorubicin 500 mg/m\^2
* HER2-low expressing cohort only: Receipt of live, attenuated vaccine (messenger ribonucleic acid \[mRNA and replication deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first dose of DS-8201a (trastuzumab deruxtecan)
* Pregnancy and individuals unwilling to discontinue nursing PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, DRUG: Docetaxel, PROCEDURE: Echocardiography Test, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Multigated Acquisition Scan, OTHER: Questionnaire Administration, BIOLOGICAL: Trastuzumab, BIOLOGICAL: Trastuzumab Deruxtecan, BIOLOGICAL: Trastuzumab Emtansine
Metastatic Salivary Gland Carcinoma, Recurrent Salivary Gland Carcinoma, Stage III Major Salivary Gland Cancer AJCC v8, Stage IV Major Salivary Gland Cancer AJCC v8, Unresectable Salivary Gland Carcinoma
Study of NALIRIFOX in Advanced Unresectable Small Bowel Tumors
Tiago Biachi de Castria, MD, PhD - tiago.biachi@moffitt.org
NCT06835387
Inclusion Criteria:
• Subject has been informed about the nature of the study, and has agreed to participate in the study, and signed the ICF prior to participation in any study-related activities. Also, as determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of ≤ 1 within 28 days prior to registration.
• Histological or cytologically confirmed small bowel adenocarcinoma per AJCC staging manual, 8th edition that has not been previously treated in the metastatic setting. Subjects treated in the adjuvant setting who completed treatment \> 6 months prior to registration and do not have residual toxicities \> Grade 1 are eligible. NOTE: Subjects with only localized disease or disease which will likely become resectable after chemotherapy (per investigator discretion) are NOT eligible.
• Mismatch repair proficient (MMRp) and/or microsatellite stable (MSS) disease per institutional standard of care testing.
• Subject has one or more metastatic lesion(s) measurable by CT scan (or MRI, if the subject is allergic to CT contrast media) according to RECIST Version 1.1 criteria. Lesions in a prior radiation field must have progressed subsequent to radiotherapy to be considered measurable.
• Demonstrate adequate organ function as defined below. All screening labs to be obtained within 28 days prior to registration. * Platelets (Plt) ≥ 100,000 cells/mm3 * Absolute Neutrophil Count (ANC) ≥ 1,500 cells/mm3; without the use of hemopoietic growth factors * Hemoglobin (Hgb) ≥ 9 g/dL * Calculated creatinine clearance ≥ 30 mL/min; Cockcroft-Gault formula for actual body weight should be used for calculation. For subjects with a body mass index (BMI) \> 30 kg/m2, adjusted body weight should be used instead * Total bilirubin ≤ 1.5 × ULN * Aspartate aminotransferase (AST) ≤ 2 × ULN; \< 5× with liver metastases * Alanine aminotransferase (ALT) ≤ 2 × ULN; \< 5× with liver metastases * Albumin ≥ 2.5 gm/dL * PT/INR and aPTT ≤ 1.5 x ULN; subjects on warfarin or other vitamin K antagonists should be discussed with the sponsor-investigator. * Urinalysis: Urinalysis results without clinically significant abnormalities, per the investigator's assessment
• Electrocardiogram (ECG) without any clinically significant findings (QT interval corrected by Fridericia's formula (QTcF) ≤450 msec and no known arrhythmias) and per the investigator's assessment.
• Females of childbearing potential must have a negative urine or serum pregnancy test within ≤ 7 days prior to registration. If a urine test is done and it is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Females of childbearing potential who are sexually active with a male able to father a child must be willing to abstain from penile-vaginal intercourse or use an effective method(s) of contraception. Males able to father a child who are sexually active with a female of childbearing potential must be willing to abstain from penile-vaginal intercourse or use an effective method(s) of contraception.
• Subjects with known human immunodeficiency virus (HIV) are eligible if they meet all the following criteria: * CD4 count is ≥350 cells/uL, viral load is undetectable, and not taking prohibited cytochrome (CYP)-interacting medications; * Probable long-term survival with HIV if cancer were not present; * Stable on a highly active antiretroviral therapy (HAART) regimen for ≥ 4 weeks and willing to adhere to their HAART regimen with minimal overlapping toxicity and drug-drug interactions with the experimental agents in this study; * HIV is not multi-drug resistant; * Taking medication and/or receiving antiretroviral therapy that does not interact or have overlapping toxicities with the study medication. NOTE: Testing for HIV is not required at screening unless mandated by local policy. If a subject is known to be HIV positive, testing is required as described above to meet eligibility requirements.
• Subjects with known chronic hepatitis B virus (HBV) infection, must have an undetectable HBV viral load on suppressive therapy, if indicated. Subjects with a history of hepatitis C virus (HCV) infection must have been treated and cured. For subjects with HCV infection who are currently on treatment, the HCV viral load must be undetectable to be eligible for this trial. NOTE: Testing for HBV and HCV is not required at screening unless mandated by local policy. If a subject is known to have an HBV and/or HCV infection, testing is required as described above to meet eligibility requirements.
Exclusion Criteria:
• Adenocarcinoma originating in the ampulla or appendix (duodenal tumors that involve the ampulla but originate in the duodenum are eligible).
• Neuroendocrine or any other histology different than adenocarcinoma.
• Prior treatment with irinotecan.
• Prior treatment of small bowel adenocarcinoma (SBA) in the metastatic setting with surgery, radiotherapy, chemotherapy or investigational therapy: * Palliative radiotherapy is permitted but lesions in a prior radiation field must have progressed subsequent to radiotherapy to be considered measurable. * Placement of biliary stent/tube is permitted. * Palliative surgery (for example to treat obstruction)
• Known history of central nervous system (CNS) metastases. (subjects on a stable or decreasing dose of steroids and deemed clinically stable as per the investigator's assessment are eligible).
• Clinically significant gastrointestinal disorder including hepatic disorders, bleeding, inflammation, occlusion, diarrhea \> Grade 1, malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, or bowel obstruction.
• Pregnant or breastfeeding. NOTE: breast milk cannot be stored for future use while the mother is being treated on study.
• Subjects with an active malignancy in the last 2 years. The following subjects may be eligible: Subjects with prior history of in-situ cancer or basal or squamous cell skin cancer. Subjects with a history of other malignancies but have been continuously disease free for at least 2 years without treatment prior to registration.
• Known hypersensitivity to any of the components of nanoliposomal irinotecan, other liposomal products, or any components of 5-FU, LV or oxaliplatin.
• Concurrent illnesses that would be a relative contraindication to trial participation such as active cardiac or liver disease, including: * Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) less than 6 months before registration * High cardiovascular risk, including, but not limited to, recent coronary stenting or myocardial infarction in the past year prior to registration * New York Heart Association (NYHA) Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure
• Active infection or an unexplained fever \>38.5°C during screening visits or on the first scheduled day of dosing (at the discretion of the investigator, subjects with tumor fever may be enrolled), which in the investigator's opinion might compromise the subject's participation in the study or affect the study outcome.
• Major surgery, other than diagnostic surgery, within 4 weeks prior to registration.
• Use of strong inhibitors or inducers of CYP3A, CYP2C8 and UGT1A1. Subjects are ineligible if: * they are unable to discontinue the use of strong inhibitors of CYP3A, CYP2C8 and UGT1A1 at least 1 week prior to registration; * they are unable to discontinue the use of strong CYP3A and CYP2C8 inducers at least 2 weeks prior to registration;
• There is presence of any contraindications outlined in the Contraindications or Warnings and Precautions sections of the IB for nanoliposomal irinotecan, or in the prescribing information for 5-FU, LV or oxaliplatin.
• Subjects who, in the opinion of the investigator, have symptoms or signs suggestive of clinically unacceptable deterioration of the primary disease at the time of screening.
• History of systemic connective tissue disorders (e.g. lupus, scleroderma, arteritis nodosa).
• Subjects who have received a live vaccine within 4 weeks prior to registration.
• History of the following: interstitial lung disease, slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies, and peripheral artery disease (e.g. claudication, Leo Buerger's disease).
• Known low or absent dihydropyridine dehydrogenase (DPD) or UGT1A1activity. Testing for DPD or UGT1A1 deficiency is not mandatory but where required by local regulations, testing must be performed using a validated method which is recommended by local health authorities.
DRUG: Nanoliposomal irinotecan, DRUG: Oxaliplatin, DRUG: 5 fluorouracil, DRUG: Leucovorin
Small Bowel Adenocarcinoma
Health indicators, training, and performance among ultra-endurance athletes
Alexandra Lempke - alexandra.lempke@vcuhealth.org
Alexandra Lempke
HM20031840
HM20031840
Comparative Effectiveness of Carvedilol Versus Metoprolol Succinate in Heart Failure Patients With an Implantable Cardioverter Defibrillator (CARVTOP-ICD)
Mehmet Aktas, M.D. - Mehmet_Aktas@URMC.Rochester.edu
NCT06964464
Inclusion Criteria:
* Age ≥ 18 years
* ICD implanted for primary prevention for HFrEF (either ICM or NICM) with remote monitoring capability
* Current treatment with metoprolol succinate and willing to switch to carvedilol
* LVEF \<50% during the past 12 months prior to consent
Exclusion Criteria:
* Unwilling or unable to follow the protocol
* Treatment with any other ßB than metoprolol succinate or no ßB treatment
* Known prior intolerance or contraindication to carvedilol
* Systolic blood pressure \<100 mmHg
* Enrollment in another clinical trial
* Inability or unwilling to consent DRUG: Metoprolol Succinate, DRUG: Carvedilol
Heart Failure With Reduced Ejection Fraction (HFrEF), Sudden Cardiac Death, Ventricular Arrhythmia, Implantable Cardioverter Defibrillator (ICD), Beta-blocker Therapy, Cardiomyopathy
arrhythmia, heart failure, ICD, implantable cardioverter defibrillator, ICD shock, carvedilol, metoprolol succinate, beta-blocker
Romosozumab as an Adjunct to Physiologic Estrogen Replacement in Functional Hypothalamic Amenorrhea
Alexandra Lempke - Alexandra.Lempke@vcuhealth.org
NCT06533865
Inclusion Criteria:
For FHA and controls:
* Female, age 14-30 years, skeletally mature with bone age ≥ 14 years (only 2% of growth left)
* For women of reproductive age, agree to use an effective non-hormonal contraceptive method or a progestin releasing intrauterine device (no evidence of systemic skeletal effects) for the study duration
* Biochemical criteria:
* Negative βHCG (pregnancy test)
* TSH within twice the upper limit of normal; potassium, magnesium within the normal range; prolactin \<10 ng/mL above the upper limit of normal; FSH not elevated.
* Serum ALT ≤ 3 times upper limit of normal, LDL ≤ 190 mg/dl
* eGFR ≥ 30ml/minute
* If the diagnosis of FHA is unclear, we may check additional labs (e.g., testosterone and sex hormone binding globulin if there is a suspicion of PCOS based on clinical hyperandrogenism).
Additional inclusion criteria for FHA:
* Less than 3 menses in the preceding 6 months
* BMD Z-score ≤ -1.0 at ≥ 1 skeletal site (for subjects \<18 years old, we will use the height Z-score-adjusted BMD Z-score using the pediatric bone density calculator developed by the National Institutes of Health and currently maintained by the Children's Hospital of Philadelphia)
* Dental check-up within the past year
* If the menstrual status of the subject is unclear due to the presence of a progestin-releasing IUD, serum estradiol levels will be checked twice, at least one week apart. Both estradiol levels must be \< 50 pg/mL.
Exclusion Criteria:
For FHA and controls
* Disease other than FHA known to affect bone, including untreated thyroid dysfunction, Cushing's disease, renal failure, diabetes mellitus
* Use of bisphosphonates
* Use of other medications known to affect bone metabolism within 3 months of the study (other than calcium and vitamin D supplementation).
* Current use of systemic corticosteroids
* Migraine with aura.
* Personal history of or first-degree relative with unprovoked thromboembolism (unless the subject has been tested and ruled out for a hypercoagulable state).
* Active substance use disorder; current smoker
* History of malignancy or Paget disease of bone
* Pregnant, planning to become pregnant within 12 months after the end of treatment and/or breastfeeding
Additional exclusion criteria for FHA
* Cardiovascular: History of myocardial infarction or stroke; history of hypertension or use of anti-hypertensive medications
* Immunodeficiency or taking immunosuppressive therapy
* Other conditions that can cause oligo-amenorrhea such as PCOS, primary ovarian insufficiency
* Dental: Osteonecrosis of the jaw (ONJ) or risk factor for ONJ, such as invasive dental procedures (tooth extraction, dental implants, oral surgery in the past 3 months), poor oral hygiene, periodontal and/or pre-existing dental disease
* Planned invasive dental procedure or other planned major surgery for 18 months after the baseline visit
* Known sensitivity or absolute contraindication to any of the products or components of the medications to be administered (romosozumab, zoledronic acid, transdermal estradiol, micronized progesterone, calcium or vitamin D supplements)
* Concerning EKG findings for ischemia
Additional exclusion criteria for normal-weight healthy controls
• BMD Z-score \<-2.5 (who we will refer for evaluation) DRUG: Romosozumab, DRUG: Placebo, DRUG: Zoledronic acid
FHA (Functional Hypothalamic Amenorrhea)
Acoramidis Transthyretin Amyloidosis Prevention Trial in the Young (ACT-EARLY) Study in Asymptomatic Carriers of a Pathogenic TTR Variant
Medical Information - medinfo@eidostx.com
NCT06563895
Key
Inclusion Criteria:
* Male or female ≥ 18 to ≤ 75 years of age inclusive.
* Participants must have an established genotype (hetero- or homozygosity) through a medically-indicated genetic test of a TTR gene variant that is known to be pathogenic or likely pathogenic (eg, V30M/p.V50M, V122I/p.V142I, T60A/p.T80A, or all other pathogenic TTR variants).
* Participant's age is within 10 years younger than or older than PADO.
Key Exclusion Criteria:
* Evidence of ATTR-CM or ATTR-PN.
* Current or past (within last 1 to 12 months, depending on specific agent) treatment with other TTR modifying therapies.
* Contraindication to or inability to undergo cardiac magnetic resonance testing.
* Major organ dysfunction, including: kidney disease, liver disease, heart disease (including cardiomyopathy), neuropathy
* Other diseases or conditions such has cancer within 5 years, untreated hyperthyroidism or hypothyroidism, type 1 diabetes, active hepatitis B or C, HIV.
* Major surgery within the past 3 months or planned during the next 12 months.
* Known hypersensitivity to acoramidis. DRUG: Acoramidis, DRUG: Placebo oral tablet
Amyloidosis, Amyloid Cardiomyopathy, Transthyretin Amyloidosis, Cardiomyopathies, Heart Diseases, Polyneuropathies
Amyloidosis, ATTR-CM, ATTR-PN, Transthyretin, Amyloid, TTR
Study of Navtemadlin add-on to Ruxolitinib in JAK Inhibitor-Naïve Patients With Myelofibrosis Who Have a Suboptimal Response to Ruxolitinib (POIESIS)
John Mei - jmei@kartosthera.com
NCT06479135
Inclusion Criteria for Ruxolitinib Alone Period:
* Confirmed diagnosis of PMF, post-PV MF, or post-ET MF, as assessed by the treating physician according to the World Health Organization (WHO) criteria
* High, Intermediate-1, Intermediate-2 risk category International Prognosis System Score (IPSS)
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
* JAK-inhibitor treatment naive
Exclusion Criteria for Ruxolitinib Alone Period:
* Prior Splenectomy
* Splenic irradiation within 3 months prior to the first dose
* Prior BCL-XL, BET, MDM2, PI3K, PIM, or XPO1 inhibitors therapy or p53-directed therapy
* Eligible for Bone Marrow Transplant
* Peripheral blood or bone marrow blast count ≥ 10 percent
Inclusion Criteria for Randomized Period:
* PMF, post-PV MF, or post-ET MF that is TP53WT as assessed by central testing
* ECOG performance status of 0 to 2
* Treatment with a stable dose of ruxolitinib
* Suboptimal response to run-in ruxolitinib treatment
Exclusion Criteria for Randomized Period:
* Elevated white blood cell count that doubles (or more) during ruxolitinib treatment and exceeds 50 × 10\^9/L
* Peripheral blood or bone marrow blast count ≥ 10 percent
DRUG: Navtemadlin, DRUG: Navtemadlin placebo, DRUG: Ruxolitinib
Myelofibrosis, Post-PV MF, Post-ET Myelofibrosis, Primary Myelofibrosis, MF
Navtemadlin, KRT-232, Ruxolitinib, POIESIS, TP53, Suboptimal response, Sub-optimal response
A Study to Evaluate the Safety and Efficacy of MK-3120 in Participants With Advanced Solid Tumors (MK-3120-002)
Toll Free Number - Trialsites@msd.com
NCT06818643
Inclusion Criteria:
* Has a confirmed advanced (unresectable and/or metastatic) solid tumor and has received or been intolerant to all available treatments
* If human immunodeficiency virus (HIV) positive, has well controlled HIV on antiretroviral therapy (ART)
* If hepatitis B surface antigen (HBsAg) positive, must have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load
* If hepatitis C virus (HCV) infected, must have undetectable HCV viral load
Exclusion Criteria:
* Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
* Has uncontrolled significant cardiovascular disease or cerebrovascular disease
* Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing
* Has pleural effusion, ascites, and/or pericardial effusion that are symptomatic or require repeated drainage
* Is HIV-positive and has a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Known additional malignancy that is progressing or has required active treatment within the past 2 years
* Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
* Active infection requiring systemic therapy, with exceptions
* History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
* Has HBV or HCV infection BIOLOGICAL: MK-3120
Advanced Solid Tumors, Malignant Neoplasm
A Study to Evaluate BMS-986470 in Healthy Volunteers and Participants With Sickle Cell Disease
BMS Clinical Trials Contact Center www.BMSClinicalTrials.com - Clinical.Trials@bms.com
NCT06481306
Inclusion Criteria
\- Cohort A.
i) Healthy male and female (who are not of childbearing potential) participants, as determined by the investigator based on medical history and other determinations. Females not of childbearing potential must have been amenorrhoeic for at least 12 months without an alternative medical cause and have follicle-stimulating hormone (FSH) levels of at least 40 IU/L or have undergone a hysterectomy, bilateral oophorectomy, or bilateral salpingectomy.
ii) Body mass index (BMI) of 18.0 to 32.0 kg/m\^2, inclusive. BMI = weight (kg)/ (height \[m\])\^2 as measured at screening.
iii) No evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG, or clinical laboratory assessments beyond what is consistent with the target population.
\- Cohort B.
i) Participants with a documented diagnosis of Sickle Cell Disease (SCD) with genotype HbSS, HbSβ0-thal, or HbSβ+-thal.
ii) Participants with ≥ 4 vaso-occlusive crises (VOCs) within the previous 12 months or ≥ 2 VOCs within the previous 6 months.
iii) Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
iv) Must have the following laboratory values:.
A. Hemoglobin ≥ 5.5 and ≤ 12 g/dL (males) or ≥ 5.5 and ≤ 10.6 g/dL (females).
B. Absolute neutrophil count ≥ 1500/μL.
C. Platelet count ≥ 100 × 10\^3/μL.
D. Absolute reticulocyte count \> 100 × 10\^3/μL or \> 50 × 10\^3/μL if taking hydroxyurea.
Exclusion Criteria
\- Cohort A.
i) Any significant medical condition or any condition that confounds the ability to interpret data from the study.
ii) Participant has any condition, including the presence of laboratory abnormalities, that places the participant at unacceptable risk if the participant was to participate in the study.
iii) Any major surgery or planned surgery (except GI surgery) within 12 weeks of the first study intervention administration.
\- Cohort B.
i) Participants with any condition, including significant acute or chronic medical illness, active or uncontrolled infection, or the presence of laboratory abnormalities, that places participants at unacceptable risk if participating in this study.
ii) Participants with more than 6 severe VOCs defined as VOCs requiring ≥ 24 hours of hospital admission within 12 months prior to the first dose of study intervention or any VOC requiring ≥ 24 hours of hospital admission within 30 days prior to the first dose of study intervention.
iii) Participants with any episode of acute chest syndrome within the last 6 months prior to the first dose of study intervention.
iv) Creatinine clearance (CrCl) \< 60 mL/min/1.72m2 using Chronic Kidney Disease Epidemiology (CKD-EPI) equation
* Cohort A and B.
i) Participant is receiving regularly scheduled RBC or platelet transfusions or has received a RBC transfusion within 28 days and a platelet transfusion within 14 days prior to starting treatment with BMS-986470.
* Other protocol-defined Inclusion/Exclusion criteria apply.
DRUG: BMS-986470, DRUG: Placebo, DRUG: Famotidine
Anemia, Sickle Cell, Healthy Volunteers
Testing the Combination of the Anti-cancer Drugs ZEN003694 (ZEN-3694) and Talazoparib in Patients With Advanced Solid Tumors, The ComBET Trial
ctrrecruit@vcu.edu
NCT05327010
Inclusion Criteria:
* Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
* Patients must have a tumor lesion that can be biopsied with 'low' or 'minimal' risk and at least one measurable disease site, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1
* Note: Tumor lesions that are situated in a previously irradiated area may or may not be considered measurable
* Patients in cohorts 1, 2, and 4 should have at least one relevant mutation. Patients enrolled in cohorts 1-3 do not require that PARP inhibitor (i) be the immediate prior therapy to be eligible for the trial. Patients should sign a screening consent that will allow the review of local next generation sequencing (NGS) or equivalent Clinical Laboratory Improvement Amendment (CLIA)-certified assay results by MD Anderson's Precision Oncology Decision Support (PODS) team to ensure that the mutations are actionable. No variants of uncertain significance (VUS) will be allowed
* Patients in Cohort 1 must have (i) a germline or somatic mutation in BRCA1 or BRCA2; and (ii) must have received prior PARPi monotherapy or PARPi combination-therapy
* Patients in Cohort 2 must have: (i) a germline or somatic mutation in any of the following deoxyribonucleic acid (DNA) damage response (DDR) genes: BARD1; FANCA; BRIP1; PALB2; RAD51; RAD51C; RAD51D, with no evidence of mutations in BRCA1 or BRCA2; and (ii) must have received prior PARPi monotherapy or PARPi combination therapy
* Patients in Cohort 3 must be (i) patients who have had PR/CR on prior PARPi monotherapy or PARPi combination treatment; and (ii) patients with no evidence of BRCA1 or BRCA2 mutations or any of the relevant DDR aberrations listed in cohort 2. Patients with ovarian cancer should not have progressed on platinum-therapy within six months of therapy
* Patients in Cohort 4 must have KRAS mutated advanced solid tumors. Prior treatments with KRAS inhibitors are permitted. Patients with KRAS G12C mutations must have already had KRAS G12C targeted therapy (e.g., sotorasib) previously
* Patients must have received at least one line of systemic therapy in the advanced/metastatic setting. Subjects with diseases without known effective options, and subjects who have declined standard of care therapy prior to study introduction, are also eligible. Patients with ovarian cancer in cohort 3 should not have progressed on platinum within six months of therapy
* Age \>= 18 years
* Because no dosing or adverse event data are currently available on the use of ZEN003694 (ZEN-3694) in combination with talazoparib in patients \< 18 years of age, children are excluded from this study
* Patients must be greater than 4 weeks (6 weeks for nitrosoureas or mitomycin C) beyond treatment with any chemotherapy or other investigational therapy including hormonal, biological, or targeted agents; or at least 5 half-lives from hormonal, biological, or targeted agents, whichever is shorter at the time of treatment initiation. Patients must have recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities =\< grade 1) with the exception of alopecia or anorexia
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
* Absolute neutrophil count \>= 1,500/mcL
* Platelets \>= 150,000/mcL
* Hemoglobin \>= 10.0 g/dL (no blood transfusions in the preceding 28 days)
* Total bilirubin 1.5 x =\< institutional upper limit of normal (ULN) OR direct bilirubin = ULN for subjects with total bilirubin levels \> 1.5 x ULN
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN
* Creatinine 1.5 x institutional ULN OR glomerular filtration rate (GFR) \>= 60 mL/min/1.73 m\^2 for subjects with creatinine levels \> 1.5 x institutional ULN, unless data exists supporting safe use at lower kidney function values, no lower than 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
* Patients with evidence of chronic hepatitis B virus (HBV) infection must have an undetectable viral load while 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 previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study enrollment, have discontinued corticosteroid treatment for these metastases for at least 2 weeks, and are neurologically stable. Patients with known symptomatic brain metastases requiring steroids are excluded. Of note, patients who required a single dose of corticosteroids on days receiving radiation treatment do not require a 2-week washout. Follow-up brain imaging after central nervous system (CNS)-directed therapy must show no evidence of progression and patient should be clinically stable for at least 1 month. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability
* 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. However, patients with concurrent malignancy that is progressing or requiring active treatment are excluded
* 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 of class 2B or better
* The effects of the combination ZEN003694 (ZEN-3694) and talazoparib on the developing human fetus are unknown. For this reason, and because BET inhibitor agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 7 months after. 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 for 7 months after completion of study drug administration
* Women of child-bearing potential MUST have a negative serum or urine human chorionic gonadotropin (HCG) test unless prior tubal ligation (\>/= 1 year before screening), total hysterectomy, or menopause (defined as 12 consecutive months of amenorrhea)
* Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
* Patients who are receiving any other investigational agents
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to ZEN003694 (ZEN-3694) or talazoparib
* Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 or P-gp, strong inhibitors of BCRP, sensitive substrates of CYP1A2, proton-pump-inhibitors (H2 antagonists are allowed), and herbal medications/preparations (vitamins are allowed) are ineligible. Strong inhibitors or inducers of CYP3A4 must be discontinued at least 7 days prior to the first dose of ZEN003694 (ZEN-3694). Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product.
* Patients with uncontrolled intercurrent illness
* Patients with psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant women are excluded from this study because ZEN003694 (ZEN-3694) is a BET inhibiting agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ZEN003694 (ZEN-3694), breastfeeding should be discontinued prior to the first dose of study drug and women should refrain from nursing throughout the treatment period and for 1 month following the last dose of the study drug. These potential risks may also apply to other agents used in this study
* Patients who are involved in the planning and/or conduct of the study
* Patients who are unable or unwilling to swallow pills
* Active infection requiring intravenous (IV) antibiotics, or other uncontrolled intercurrent illness requiring hospitalization
* Patients receiving any medications or substances that are factor Xa inhibitors (i.e., rivaroxaban, apixaban, betrixaban, edoxaban otamixaban, letaxaban, eribaxaban) and factor IIa inhibitors (i.e., dabigatran). Low molecular weight heparin is allowed
* Patients with radiation to \> 25% of the bone marrow
* Patients who have had a bone-targeted radionuclide within 6 weeks of the first dose of ZEN003694 (ZEN-3694) or talazoparib
* Patients who have previously received ZEN003694 (ZEN-3694) or who have been treated with an investigational BET inhibitor
* Patients with cerebrovascular accident (CVA), myocardial infarction, or unstable angina within 6 months prior to the first dose of ZEN003694 (ZEN-3694) or talazoparib
* Patients with impairment of gastrointestinal function that may significantly alter the absorption of ZEN003694 (ZEN-3694) or talazoparib
* Patients that have had major surgery other than diagnostic surgery, dental surgery, or stenting within 4 weeks prior to the first dose of ZEN003694 (ZEN-3694) or talazoparib DRUG: BET Bromodomain Inhibitor ZEN-3694, PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, PROCEDURE: Diagnostic Imaging Testing, DRUG: Talazoparib
Advanced Malignant Solid Neoplasm, Metastatic Malignant Solid Neoplasm, Unresectable Malignant Solid Neoplasm
Strategy for Improving Stroke Treatment Response (SISTER)
Rebeca Aragon Garcia, BS, CCRC - aragonra@ucmail.uc.edu
NCT05948566
Inclusion Criteria:
• Age 18 years and older
• Suspected anterior circulation acute ischemic stroke
• NIH Stroke Scale score ≥4 prior to randomization a. The participant must have a clearly disabling deficit if NIHSS is 4-5.
• Favorable baseline neuroimaging consisting of all of the following:
• ASPECTS of 6 or more on CT (or ASPECTS of ≥7 on MRI)
• Favorable perfusion imaging on CT perfusion (CTP)/MR-perfusion weighted imaging (PWI) consisting of all of the following: i. Mismatch ratio of penumbra: core \>1.2 ii. Mismatch volume \>10 cc iii. Core \<70 cc c. If CT hypodensity is present, then in the investigator's visual assessment, the total acute infarct volume combined area of (a) the CT hypodensity and (b) the perfusion-based core volume (CBF\<30%) should be smaller than perfusion-based volume (area of Tmax\>6s minus CBF\<30%).
• Able to receive assigned study drug within 4.5 to 24 hours of stroke onset or last known well.
• Able to receive assigned study drug within 120 minutes of qualifying perfusion imaging. \*
• Informed consent for the study participation obtained from participant or their legally authorized representatives. * Study drug administration is encouraged within 90 minutes after qualifying perfusion image but is allowed up to 120 minutes. After 120 minutes, another perfusion image to ensure that inclusion criteria are met is required.
Exclusion Criteria:
• Received endovascular treatment with clot engagement.
• Patients who undergo groin puncture but clot engagement is not attempted due to spontaneous distal migration are permitted to be enrolled in the trial if all other eligibility criteria are met.
• Patients who undergo groin puncture but clot is not engaged due to reasons other than spontaneous distal migration are NOT permitted.
• Received or planned to receive intravenous thrombolysis.
• Pre-stroke modified Rankin score \>2.
• Previous treatment with TS23 or known previous allergy to antibody therapy.
• Known pregnancy, women who are breastfeeding or plan to breastfeed within 3 months of receiving TS23 or have a positive urine or serum pregnancy test for women of childbearing potential.
• Known previous stroke in the past 90 days.
• Known previous intracranial hemorrhage, intracranial neoplasm, subarachnoid hemorrhage, or arterial venous malformation.
• Known active diagnosis of intracranial neoplasm.
• Clinical presentation suggestive of a subarachnoid hemorrhage, even if initial CT scan was normal.
• Surgery or biopsy of parenchymal organ in the past 30 days.
• Known trauma with internal injuries or persistent ulcerative wounds in the past 30 days.
• Severe head trauma in the past 90 days.
• Persistent systolic blood pressure \>180mmHg or diastolic blood pressure \>105mmHg despite best medical management.
• Serious systemic hemorrhage in the past 30 days.
• Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with International Normalized Ratio (INR) \>1.7.
• Platelets \<100,000/mm3.
• Hematocrit \<25 %.
• Elevated aPTT above laboratory upper limit of normal.
• Creatinine \> 4 mg/dl, or patients receiving renal dialysis, regardless of creatinine.
• Received the following within the previous 24 hours:
• If patient received unfractionated heparin within the last 24 hours, the patient must have an aPTT within normal range prior to enrollment.
• Low molecular weight heparins such as Dalteparin, enoxaparin, tinzaparin in full dose within the previous 24 hours.
• Received Factor Xa inhibitors (such as Fondaparinux, apixaban or rivaroxaban) within the past 48 hours.
• Received direct thrombin inhibitors (e.g., argatroban, dabigatran, bivalirudin, desirudin, lepirudin) within 48 hours.
• Received glycoprotein IIb/IIIa inhibitors within the past 14 days.
• Known pre-existing neurological or psychiatric disease which would confound the neurological/functional evaluations.
• Current participation in another research drug treatment protocol (i.e., participants could not start another experimental agent until after 90 days).
• Concurrent acute myocardial infarction, pulmonary embolism, deep venous thrombosis or other thrombotic event that requires anticoagulation or anti-platelet treatment.
BIOLOGICAL: TS23
Ischemic Stroke
CLEOPATTRA: A Research Study to Look at the Effects of Treatment With a Medicine Called Coramitug (NNC6019-0001) in People With Heart Failure Due to Transthyretin Amyloid (ATTR) Amyloidosis (CLEOPATTRA)
Novo Nordisk - clinicaltrials@novonordisk.com
NCT07207811
Inclusion Criteria:
* Male or female.
* Age 18 years or above at the time of signing the informed consent.
* Have an established diagnosis of ATTR-CM (wild-type ATTR \[ATTRwt\] or variant ATTR \[ATTRv\]), with cardiac amyloid infiltration, increased left ventricular (LV) wall thickness, and HF.
Note: Target ATTRv recruitment is approximately 15 percent of the study population.
• Cardiac amyloid infiltration demonstrated by: * Cardiac biopsy positive for TTR amyloid, OR * Grade 2 or 3 cardiac uptake at pyrophosphate (PYP)/diphosphono-1,2-propanodicarboxylic acid (DPD)/ hydroxymethylene diphosphonate (HMDP) nuclear medicine imaging with single-photon emission computed tomography (SPECT) or SPECT/CT (preferably) combined with an extracardiac biopsy positive for TTR amyloid, OR * Grade 2 or 3 cardiac uptake at PYP/DPD/HMDP nuclear medicine imaging with SPECT or SPECT/CT (preferably) combined with normal serum free light chain ratio, and negative serum and urine protein electrophoresis with immunofixation (SPIE \& UPIE)/or mass spectrometry based methods including mass fixation). Notes: * Non-invasive diagnostic pathway will be confirmed by a centralised expert review. * Bone tracer nuclear medicine imaging with SPECT or SPECT/CT (preferably) will be conducted using 99m-technetium (Tc)-labelled pyrophosphate (99mTc-PYP), 99mTc-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD), or 99mTc-labeled hydroxymethylene diphosphonate (99mTc-HMDP). * The eGFR adjusted acceptable serum free light chain ratio. * Patients with Grade 2 or 3 cardiac uptake at PYP/DPD/HDMP nuclear imaging with SPECT or SPECT/CT (preferably) and evidence of monoclonal gammopathy of undetermined significance (MGUS; based on serum and urine protein electrophoresis and serum free light chains) will require endomyocardial biopsy with typing using mass spectrometry or immunohistochemistry to confirm presence of TTR protein in tissue. * Timing of serum free light chain ratio, SPIE, UPIE and mass spectrometry-based methods including mass fixation should be within 12 months of SPECT or SPECT/CT nuclear imaging.
• Increased LV wall thickness, as assessed by centralised review of echocardiography, showing interventricular septal wall thickness greater than or equal to 12 millimeter (mm).
• Chronic HF (New York Heart Association \[NYHA\] Class I-IV): * At least 1 documented hospitalisation for HF, OR * History of HF manifested by signs or symptoms of volume overload or elevated intracardiac pressures (e.g., elevated jugular venous pressure, shortness of breath, signs of pulmonary congestion on x-ray or auscultation, or peripheral oedema that required or requires ongoing treatment with a diuretic). * Expected to be on stable cardiovascular medical therapy (defined as no greater than 50 percent dose adjustment and no categorical changes of medications), with the exception of diuretics, 4 weeks prior to the randomisation visit. * Completed more than 50 meters on the 6MWT at screening.
Exclusion Criteria:
* Known or suspected hypersensitivity to study intervention(s) or related products.
* Current or previous participation (dosing with active treatment) in a study for an investigational ATTR depleting drug or ATTR gene editing therapy.
* Total bilirubin greater than 3 times the upper limit of normal (ULN) at screening.
* Current diagnosis or history of amyloid light chain, other non-ATTR amyloidosis, known leptomeningeal amyloidosis, or multiple myeloma.
* HF not primarily caused by ATTR-CM (e.g., due to hypertension, valvular heart disease, or ischemic heart disease in the opinion of the investigator).
* Currently hospitalised or hospitalised within 14 days prior to screening.
* Currently treated with positive inotropic medication.
* Uncorrected, severe, haemodynamically significant, left-sided heart valve disease.
* Acute coronary syndrome, unstable angina, stroke, transient ischemic attack, coronary revascularisation, cardiac device implantation, cardiac valve repair, or major surgery within 60 days of screening.
* Prior solid organ transplant or planned solid organ transplant during the study.
* Left ventricular ejection fraction (LVEF) less than 30 percent as assessed by centralised review of echocardiography.
* Presence or history of malignant neoplasm (other than basal or squamous cell skin cancer, in situ carcinomas of the cervix, carcinoma in situ/high-grade prostatic intraepithelial neoplasia \[PIN\], low-risk prostate cancer, or on stable therapy for prostate cancer) within 3 years before screening.
* End-stage renal disease (estimated glomerular filtration rate \[eGFR\] less than 15 mL/min/1.73 m\^2 at screening, or chronic/intermittent haemodialysis or peritoneal dialysis). DRUG: NNC6019-0001, DRUG: Placebo (NNC6019-0001)
Transthyretin Amyloid Cardiomyopathy (ATTR CM)
Testing the Effectiveness of a Combination Targeted Therapy (ViPOR) for Patients With Relapsed and/or Refractory Aggressive B-cell Lymphoma
ctrrecruit@vcu.edu
NCT06649812
Inclusion Criteria:
* Patient must be ≥ 18 years of age
* Patient must have histologically or cytologically confirmed aggressive B-cell lymphoma as follows:
* Cohort 1: CD10-negative DLBCL, which includes:
* CD10-negative non-GCB DLBCL, not otherwise specified (NOS) (i.e., CD10-/BCL6- or CD10-/BCL6+/MUM1+ DLBCL)
* CD10-negative GCB DLBCL, NOS (i.e., CD10-/BCL6+/MUM1- DLBCL)
* CD10-negative HGBCL with MYC and BCL6 (without BCL2) translocations (HGBCL-DH-BCL6)
* CD10-negative HGBCL, NOS (without MYC and BCL2 translocations)
* CD10-negative T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) OR
* Cohort 2: CD10-positive or negative HGBCL with MYC and BCL2 rearrangements (with or without BCL6 rearrangement) (HGBCL-DH-BCL2)
* NOTE: The site principal investigator must review and verify the pathology report findings to ensure the patient is eligible and is assigned to the respective cohort at the time of registration
* Patient must have relapsed and/or refractory disease after at least 1 prior anthracycline and anti-CD20 antibody-containing regimen
* Patient must not have confirmed or suspected primary mediastinal large B-cell lymphoma (PMBL)
* Patient must not be pregnant due to the potential harm to an unborn fetus with the treatment regimens being used.
* All patients of childbearing potential must have a serum or urine study with a sensitivity of at least 25 mIU/mL within 14 days prior to registration to rule out pregnancy and again within 24 hours prior to starting cycle 1 day 1 of treatment.
* A patient of childbearing potential is defined as anyone, regardless of whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Patients of childbearing potential must not expect to conceive children by abstaining from sexual intercourse or by using accepted and effective methods of contraception throughout the entire duration of protocol treatment, including during dose interruptions, and for 6 months after the last dose of protocol treatment. Male patients must not father children by abstaining from sexual intercourse or by using a condom during sexual contact with pregnant partners or partners of childbearing potential throughout the entire duration of protocol treatment, including dose interruptions, and for 6 months after the last dose of protocol treatment even if they have had a successful vasectomy
* Male patients must agree to not donate semen or sperm during the entire duration of protocol treatment or for at least 28 days after the last dose of lenalidomide
* Patient must agree to abstain from breastfeeding during the entire duration of protocol treatment and for at least 6 months after the last dose of protocol treatment
* Patient must agree to abstain from donating blood during the entire duration of protocol treatment and for at least 28 days after the last dose of lenalidomide
* Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
* Absolute neutrophil count (ANC) ≥ 1,000/mcL without requirement for granulocyte colony stimulating factor (G-CSF) support (obtained ≤ 7 days prior to registration)
* Hemoglobin ≥ 8 g/dL (obtained ≤ 7 days prior to registration)
* Platelets ≥ 75,000/mcL without requirement for platelet transfusion support (obtained ≤ 7 days prior to registration)
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (or ≤ 3.0 x institutional ULN for patients with documented Gilberts syndrome) (obtained ≤ 7 days prior to registration)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3.0 x institutional ULN (obtained ≤ 7 days prior to registration)
* Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 30 mL/min/1.73 m\^2 (estimated by Cockcroft-Gault method or measured) (obtained ≤ 7 days prior to registration)
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration 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
* Patient must not have confirmed or suspected primary DLBCL of the central nervous system (CNS) (PCNSL)
* Patients with history of secondary CNS lymphoma (SCNSL) 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
* Patient must not have taken or require warfarin or other strong CYP3A inhibitors or inducers within 7 days prior to registration.
* NOTE: Antiplatelet agents, other anticoagulants aside from warfarin, as well as mild or moderate CYP3A inhibitors or inducers are permitted on study but should be used with caution
* Patient must not have an uncontrolled intercurrent illness that would interfere with the safety or efficacy assessment of this protocol
* Patient must not have evidence of an active infection at the time of registration
* Patient must not have the following current or prior anti-cancer treatment:
* Any chemotherapy, targeted therapy, anti-cancer antibodies, antibody-drug conjugates, or bi-specific antibodies received within 2 weeks prior to registration
* NOTE: Short courses of corticosteroids or palliative external beam radiation therapy (XRT) prior to registration are permitted
* More than 3 prior lines of cytotoxic chemotherapy, excluding targeted therapy, anti-cancer antibodies, antibody-drug conjugates, bi-specific antibodies, and radio- or toxin-immunoconjugates
* NOTE: Cytoreductive chemotherapy followed by autologous stem cell transplant (ASCT) counts as 1 line of cytotoxic therapy. Similarly, cytoreductive chemotherapy (either pre-T-cell collection or as bridging therapy) followed by pre-conditioning therapy/chimeric antigen receptor T-cell (CAR-T) counts as 1 line of therapy, as long as no disease progression occurs between interventions. For both therapies, if progressive disease is documented between 2 distinct regimens, then they should be counted as 2 lines of cytotoxic chemotherapy
* Radio- or toxin-immunoconjugates within 10 weeks prior to registration
* Previous treatment with more than one of the following study agents: venetoclax, ibrutinib, or lenalidomide
* Prior autologous stem cell transplant (ASCT), chimeric antigen receptor T-cell (CAR-T) therapy, or allogeneic stem cell (or other organ) transplant within 3 months prior to registration
* Any evidence of active graft-versus-host disease or requirement for immunosuppressants within 28 days prior to registration
* NOTE: In addition, patient must have recovered (i.e., ≤ grade 1 or baseline) from all adverse events due to previously administered anti-cancer treatment, surgery, or procedure
* NOTE: Exceptions to this include events not considered to place the patient at unacceptable risk of participation in the opinion of the treating investigator (i.e., alopecia)
* 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
* Patient must have adequate formalin fixed paraffin embedded (FFPE) tumor tissue specimen from the initial diagnostic biopsy or on-study repeat tumor tissue biopsy for molecular analysis
* NOTE: Excisional tumor biopsy is preferred. Core needle biopsies will be considered adequate if there is enough tissue for the mandatory molecular analysis. Submission of an entire FFPE tumor block is preferred, but if unavailable 10 x 10um FFPE scrolls may be submitted as an alternative. If adequate archived FFPE tumor tissue is unavailable, the patient must be willing to undergo research biopsy for molecular analysis
* Patient must have measurable disease
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2 PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Bone Marrow Biopsy, PROCEDURE: Computed Tomography, DRUG: Ibrutinib, DRUG: Lenalidomide, PROCEDURE: Magnetic Resonance Imaging, BIOLOGICAL: Obinutuzumab, PROCEDURE: Positron Emission Tomography, DRUG: Prednisone, DRUG: Venetoclax
High Grade B-Cell Lymphoma With MYC and BCL6 Rearrangements, Recurrent Diffuse Large B-Cell Lymphoma, Recurrent Diffuse Large B-Cell Lymphoma Germinal Center B-Cell Type, Recurrent Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, Recurrent High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, Recurrent High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements, Recurrent High Grade B-Cell Lymphoma, Not Otherwise Specified, Recurrent T-Cell/Histiocyte-Rich Large B-Cell Lymphoma, Refractory Diffuse Large B-Cell Lymphoma, Refractory Diffuse Large B-Cell Lymphoma Germinal Center B-Cell Type, Refractory Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, Refractory High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, Refractory High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements, Refractory High Grade B-Cell Lymphoma, Not Otherwise Specified, Refractory T-Cell/Histiocyte-Rich Large B-Cell Lymphoma
Kidney Transplant Preemptive Therapy or Prophylaxis for CMV Prevention in D+R Recipients (KPoP)
Megan Gish - megan.gish@ucsf.edu
NCT06798909
Inclusion Criteria:
• Subject or legally authorized representative has provided written informed consent.
• Age ≥ 18 years of age at the time of informed consent.
• Negative for IgG antibody to CMV as assessed in a CLIA-certified laboratory between 28 days prior to transplant and up to 7 days post-transplant but prior to randomization.
• Received a kidney transplant from a CMV seropositive (IgG positive) donor in the past 7 days prior to enrollment
• Individuals of reproductive (childbearing) potential must have a negative pregnancy test (serum or urine) collected prior to randomization (SOC results within 7 days prior to transplant may be used), and must also agree to use a medically approved method of contraception. Acceptable methods include: barrier method, intrauterine device (hormonal or non-hormonal), oral hormonal contraceptives, abstinence from the time of enrollment through until discontinuation of ganciclovir or valganciclovir in either arm during the intervention period. NOTE: Individuals of reproductive potential are defined as individuals who have reached menarche and who have not been post-menopausal for at least 12 consecutive months with follicle stimulating hormone (FSH) ≥40 IU/mL or 24 consecutive months if an FSH is not available, i.e., who have had menses within the preceding 24 months, and have not undergone a sterilization procedure (e.g., hysterectomy, bilateral oophorectomy, or salpingectomy).
• If male, must agree to practice a barrier method of contraception or abstinence from the time of enrollment through 3 months after discontinuation of ganciclovir or valganciclovir in either arm during the intervention period.
Exclusion Criteria:
• In the opinion of the investigator, participants who are unable or unwilling to undergo preemptive therapy protocol (weekly CMV PCR, etc.)
• Patients who are breastfeeding or planning to breastfeed within 6 months post-transplant
• Allergy to valganciclovir/ganciclovir or Letermovir
• Receipt of immunoglobulin or CMV-specific immunoglobulin within the last 3 months (this includes COVID convalescent plasma)
• Currently enrolled or anticipated enrollment in another interventional study that, in the opinion of scientific leadership team, could affect evaluation of the primary safety and/or efficacy outcomes.
• Most recent platelet count post-transplant \<25,000/uL
• Most recent ANC performed post-transplant \<1000/uL
• Multi-organ transplant (except simultaneous kidney-pancreas) within the past 7 days
• Prior or planned receipt of a hematopoietic cell transplant
• Baseline immunodeficiency prior to transplant, including but not limited to:
• Known or suspected HIV infection
• Congenital or acquired immunodeficiency
• Unacceptable immunosuppression
• Receipt of desensitization therapy prior to kidney transplant, or
• Receipt of an ABO-incompatible kidney transplant except A2 to blood type B
DRUG: Valganciclovir (Pre-emptive CMV Therapy), DRUG: Valganciclovir CMV Prophylaxis
Cytomegalovirus (CMV), Kidney Transplant, Complications, Kidney Diseases
A Study of Tacrolimus/Methotrexate/Ruxolitinib Versus Post-Transplant Cyclophosphamide/Tacrolimus/Mycophenolate Mofetil in Non-Myeloablative/Reduced Intensity Conditioning Allogeneic Peripheral Blood Stem Cell Transplantation (BMT CTN 2203)
Incyte Corporation Call Center (US) - medinfo@incyte.com
NCT06615050
Inclusion Criteria:
* Age 18.0 years or older at the time of enrollment.
* Participants undergoing allogeneic HCT for one of the following indications:
* Acute leukemia or chronic myelogenous leukemia with no circulating blasts and with less than 5% blasts in the bone marrow. Therapy related myeloid neoplasms are allowed.
* Myelodysplasia/chronic myelomonocytic leukemia with no circulating blasts and with less than 10% blasts in the bone marrow (higher blast percentage allowed in MDS due to lack of differences in outcomes with \< 5% versus 5-10% blasts in this disease). Therapy related myeloid neoplasms are allowed.
* Lymphoma \[follicular lymphoma, Hodgkin lymphoma, diffuse large B cell lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma, angioimmunoblastic T-cell lymphoma and anaplastic large cell lymphoma\].
* Planned NMA/reduced intensity conditioning regimen.
* Participants must have a related or unrelated PBSC donor as follows:
* Sibling donor must be a 6/6 match for HLA-A and -B at intermediate (or higher) resolution, and -DRB1 at high resolution using DNA-based typing and must be willing to donate peripheral blood stem cells and meet institutional criteria for donation. HLA-matched parents and children may be used as donors.
* Unrelated donor must be a 7/8 or 8/8 match at HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing. Unrelated donor must be willing to donate peripheral blood stem cells and meet NMDP criteria for donation.
* Donor selection must comply with 21 CFR 1271.
* Cardiac function: Left ventricular ejection fraction at least 45%.
* Estimated glomerular filtration rate greater than 60 ml/min/1.73 m2 using the 2021 CKD-EPI formula Note: For eligibility, GFR by 2021 CKD-EPI is required. A baseline creatinine clearance by Cockcroft-Gault should be done to establish baseline CrCl for ruxolitinib dosing.
* Pulmonary function: DLCO corrected for hemoglobin at least 40% and FEV1 predicted at least 50%.
* Liver function: AST/ALT \< 3x ULN; Total bilirubin \< 2 mg/dL excluding Gilbert's syndrome or hemolysis.
* Karnofsky Performance Score of at least 60%.
* Female participants (unless postmenopausal for at least one year before the screening visit, or surgically sterilized), agree to practice two effective methods of contraception at the same time, or agree to completely abstain from heterosexual intercourse, from the time of signing the informed consent through 15 months post-transplant. Fertility preservation methods will be left to institutional standards.
* Male participants (even if surgically sterilized), of partners of women of childbearing potential must agree to one of the following: practice effective barrier contraception or abstain from heterosexual intercourse from the time of signing the informed consent through 15 months post-transplant.
* Plans for the use of targeted small molecule inhibitor post-transplant maintenance therapy must be disclosed upon enrollment and must be used irrespective of the outcome of the randomization. Planned use of investigational maintenance agents is not permitted. Planned hypomethylating agents as maintenance therapy is not permitted.
* Voluntary written consent obtained prior to the performance of any study-related procedure that is not a part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.
Exclusion Criteria:
* Prior allogeneic transplant.
* Active CNS involvement by malignant cells.
* Participants with secondary AML arising from myeloproliferative neoplasms or secondary AML arising from overlap syndromes, including CMML and MDS/MPN syndromes; participants with secondary AML arising from myelodysplastic neoplasm are eligible.
* Participants with primary, post-Essential Thrombocythemia (post-ET) and post-Polycythemia Vera (post-PV) myelofibrosis.
* Participants with uncontrolled bacterial, viral, or fungal infections (currently taking medication and with progression or no clinical improvement) at time of enrollment.
* Active or inadequately treated latent infection with Mycobacterium tuberculosis (i.e., TB).
* Presence of clinically significant fluid collection (ascites, pleural or pericardial effusion) that interferes with methotrexate clearance or makes methotrexate use contraindicated.
* Participants seropositive for human immunodeficiency virus (HIV) with detectable viral load. HIV+ participants with an undetectable viral load on antiviral therapy are eligible.
* Evidence of uncontrolled hepatitis B virus (HBV) or hepatitis C virus (HCV). The study allows:
* Positive HBV serology with undetectable viral load and ongoing antiviral prophylaxis to prevent potential HBV reactivation.
* Positive HCV serology with quantitative PCR for plasma HCV RNA below the lower limit of detection, with or without concurrent antiviral HCV treatment.
* Arterial or venous thrombosis including DVT, PE, stroke, and myocardial infarction within six (6) months prior to enrollment or New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia. Catheter-associated DVT is not exclusionary.
* Female participants who are pregnant (as per institutional practice) or lactating.
* Participants with a serious medical or psychiatric illness likely to interfere with participation in this clinical study.
* Participants with prior malignancies except resected non-melanoma skin cancer or treated cervical carcinoma in situ. Cancer treated with curative intent ≥ 5 years previously will be allowed. Cancer treated with curative intent \< 5 years previously must be reviewed and approved by the Protocol Officer or Chairs.
* Planned use of ATG or alemtuzumab in conditioning regimen.
* Planned use of prophylactic donor leukocyte infusions.
* Prior use of ruxolitinib.
* Prior use of immune checkpoint inhibitors (i.e., PD1, PDL1, CTLA4 modulators) within six (6) months prior to conditioning.
* For participants with 7/8 HLA-matched donors:
* Donor specific antibodies (DSAs) directed at the mismatched donor allele.
* Any use of desensitization protocols.
* Treatment with any other Investigational Medicinal Product (IMP) is not allowed while on study treatment. An IMP is defined as medications without any known FDA or EMA approved indications. DRUG: Tacrolimus (Tac), DRUG: Methotrexate (MTX), DRUG: Ruxolitinib (Rux), DRUG: Cyclophosphamide, DRUG: Mycophenolate mofetil (MMF)
Graft-versus-host Disease (GVHD)
Graft-versus-host Disease (GVHD), Chronic GvHD (cGvHD), steroid-refractory, ruxolitinib, Janus kinase inhibitor
Redefining BMI: The Body, Mind, and Inflammation Trial
Vivian Hunter - huntervr@vcu.edu
NCT06532747
Inclusion Criteria:
* Ages 18-25 years
* Body mass index (BMI) 25-50 kg/m\^2
* Female
Exclusion Criteria:
* Currently pregnant or lactating
* Current involvement in a weight loss program or current use of weight loss medication
* Lost \>5% of their body weight in the previous 3 months
* Uncontrolled medical conditions that may pose a safety issue given the recommendations for the diet and unsupervised physical activity
* Diagnosis of type 2 diabetes and/or impaired fasting blood glucose
* Diagnosis of type 1 diabetes
* Rheumatologic and gastrointestinal conditions associated with severe systemic inflammation
* Medical conditions resulting in known perturbations in the hypothalamic-pituitary-adrenal axis
* Report of a heart condition, chest pain during periods of activity or rest, or loss of consciousness
* Current or recent (during the past 3 months) use of medications that may impact weight or metabolic function
* Current or recent (during the past 3 months) use of anti-inflammatory medications
* Report of diagnosis or history of Anorexia Nervosa or Bulimia Nervosa, or any compensatory behaviors within the previous 3 months
* Hospitalization for depression or other psychiatric disorder within the past 12 months
* Uncontrolled bipolar disorder or psychotic disorder
* Current suicidal intent
* Planning to move from the area within the study period
* Unwilling to be randomized to either study condition
* Unable to read and speak English BEHAVIORAL: Integrated Lifestyle Intervention (ILI), BEHAVIORAL: Monitoring with digital tools
Obesity, Adiposity
BMI, Emerging Adult (EA) Women, Lifestyle Intervention, Biomarker Inflammation Improvement
The Diaphragmatic Initiated Ventilatory Assist (DIVA) Trial (DIVA)
Elizabeth Foglia - FOGLIA@email.chop.edu
NCT05446272
Inclusion Criteria:
* Gestational age of 23 0/7- 28 6/7 weeks at birth
* Intubated in the first 7 days of life
* Undergoing extubation following at least 12 hours of invasive mechanical ventilation
* Post-natal age \<32 weeks Post menstrual age at time of extubation
Exclusion Criteria:
* Major congenital anomalies, including pulmonary hypoplasia
* Neurologic disorders affecting respiratory drive (other than apnea of prematurity)
* Esophageal bleeding or other contraindication to NG/OG catheter placement
* Current weight \<500 grams (based on Edi catheter approval)
* Study ventilator not available at time eligibility criteria are met
* Planned surgery or invasive procedure within 5 days of extubation
* Informed consent not provided DEVICE: NIV-NAVA, DEVICE: NS-NIPPV
Extubation Failure, Bronchopulmonary Dysplasia, Death
Optimal Ventilation for Cardiac Arrest (OPTI-VENT)
CHOP RSC Clinical Research Program Manager - grahamk1@chop.edu
NCT07114510
Inclusion Criteria:
* Invasive airway in place at the start of CPR or airway placed within the first 5 minutes
* Received at least 1 minute of CPR.
Exclusion Criteria:
* Lack of commitment to aggressive ICU therapies (e.g., CPR performed as part of end-of-life care.
* Brain death determination prior to the CPR event.
* Out-of-hospital cardiac arrest was the reason for initial admission to the hospital (known poor outcomes).
* Supported by Veno-Arterial Extra Corporeal Membrane Oxygenation at the start of CPR OTHER: OPTI-VENT Bundle, OTHER: Transition, OTHER: None - control
Cardiac Arrest (CA)
Pediatric
Testing the Combination of Venetoclax and Rituximab, in Comparison to the Usual Treatment (Ibrutinib Plus Rituximab or Zanubrutinib Alone) for Waldenstrom's Macroglobulinemia/Lymphoplasmacytic Lymphoma
ctrrecruit@vcu.edu
NCT04840602
Inclusion Criteria:
* Participants must have had a confirmed diagnosis of Waldenstrom's macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL). Participants must have measurable disease as determined by IgM protein quantification.
* IgM Spike: ≥ 500 mg/dL (≥ 5 g/L)
* Extramedullary disease: The manifestation of a lymphoid mass outside of the bone marrow, resulting in enlargement in extramedullary organs such as the lymph nodes or spleen. Note: all participants must have measurable IgM spike, but are not required to have extramedullary disease
* Testing to establish baseline disease status must be performed within 28 days prior to registration
* Participants must have at least one of the criteria to require therapy for WM including:
* Anemia
* Thrombocytopenia
* Neuropathy related to WM
* Symptomatic hyperviscosity or serum viscosity levels ≥ 4.0 centipoises
* WM associated glomerulonephritis or renal disease, bulky disease, or constitutional symptoms
* Constitutional symptoms can be described as:
* Unintentional weight loss \>= 10% within the previous 6 months prior to screening
* Fevers higher than 100.5 degrees Fahrenheit (F) or 38.0 degrees Celsius (C) for 2 or more weeks prior to screening without evidence of infection
* Night sweats for more than 1 month prior to screening without evidence of infection
* Clinically relevant fatigue which is not relieved by rest due to WM
* Participants who require ongoing use or received a moderate or strong CYP3A inducer, moderate or strong CYP3A inhibitor, P-gp inhibitor within 7 days prior to the first dose of study drug will be excluded from the study. If such participants can be safely switched to an alternative agent, then the participants will be eligible to enroll
* Participants must not have had prior systemic therapy. Prior therapy with rituximab will be allowed as long as the last rituximab dose was at least 6 months prior to registration
* Participants must be \>= 18 years of age
* Participants must have history and physical exam within 28 days prior to registration
* Participants must have Zubrod performance status =\< 2
* Participants must have evidence of adequate renal function, as defined by creatinine clearance (CrCl) \>= 30 mL/min. Values must be obtained within 14 days prior to registration
* Total bilirubin =\< 1.5 x IULN (institutional upper limit of the norm) (within 14 days prior to registration)
* Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =\< 3 x IULN (within 14 days prior to registration)
* Alkaline phosphatase =\< 3 x IULN (within 14 days prior to registration)
* Platelet count \>= 50,000 cells/mm\^3 (within 14 days prior to registration)
* NOTE: Transfusion and/or growth factor support is allowed up to 7 days prior to registration
* Hemoglobin \>= 7.0 g/dL (within 14 days prior to registration)
* NOTE: Transfusion and/or growth factor support is allowed up to 7 days prior to registration
* Absolute neutrophil count (ANC) \>= 1,000 cells/mm\^3 (within 14 days prior to registration)
* NOTE: Transfusion and/or growth factor support is allowed up to 7 days prior to registration
* Participants with known human immunodeficiency virus (HIV)-infection are eligible providing they are on effective anti-retroviral therapy and have undetectable viral load at their most recent viral load test and within 6 months prior to registration
* Participants must be able to take and swallow oral medication (capsules) whole. Participants may not have any known impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of the study drug (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
* Participants must not be intolerant to rituximab
* Participants must not have known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding localized skin and nail bed fungal infections) at study enrollment, or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) 4 weeks prior to registration
* Participants must not be seropositive for hepatitis C (except in the setting of sustained virologic response, defined as undetectable viral load at least 12 weeks after completion of antiviral therapy). Hepatitis C virus (HCV) testing is only required if clinically indicated or if the participant has a history of HCV
* Participants must not consume grapefruit, Seville oranges or starfruit within 3 days prior to the first dose of venetoclax
* Participants must not be pregnant or nursing because venetoclax has not been studied in pregnant or nursing women and the mechanism of action is expected to cause fetal harm. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" e.g., implants, injectables, combined oral contraceptives, some intrauterine devices \[IUDs\], complete abstinence, or sterilized partner) and a barrier method (e.g., condom, cervical ring, sponge, etc.). This also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate participant chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures throughout the study and for at least 30 days after competition of therapy
* No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the participant is currently in complete remission, or any other cancer from which the participant has been disease free for two years or watchful waiting is appropriate in the opinion of the treating physician. Also, malignancy that in the opinion of the investigator, is considered cured with minimal risk of recurrence within 5 years, is permissible consideration of eligibility for this trial
* Participants must be offered the opportunity to participate in specimen banking
* 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
* As a part of the Oncology Participant Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
* CROSSOVER CRITERIA: Participants must have been registered and received treatment in the IR/Z or VR arm and must show progression of disease at any time during cycles 3-24
* CROSSOVER CRITERIA: In case of transformation to intermediate or high-grade lymphoma or development of Bing-Neel syndrome the participants will not undergo registration step 2 crossover and will be taken off the study
* CROSSOVER CRITERIA: Participants must have Zubrod performance status =\< 2
* CROSSOVER CRITERIA: Participants must have evidence of adequate renal function, as defined by creatinine clearance (CrCl) \>= 30 mL/min. Values must be obtained within 14 days prior to registration
* CROSSOVER CRITERIA: Participants must have no evidence of marked hepatic dysfunction on any recent liver function tests within 14 days prior to registration
* CROSSOVER CRITERIA: Platelet count \>= 50,000 cells/mm\^3 (without within 14 days prior to registration)
* NOTE: Transfusion and/or growth factor support is allowed up to 7 days prior to registration
* CROSSOVER CRITERIA: Hemoglobin \>= 7.0 g/dL (without within 14 days prior to registration)
* NOTE: Transfusion and/or growth factor support is allowed up to 7 days prior to registration
* CROSSOVER CRITERIA: Absolute neutrophil count (ANC) \>= 1,000 cells/mm\^3 (without within 14 days prior to registration)
* NOTE: Transfusion and/or growth factor support is allowed up to 7 days prior to registration PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Bone Marrow Biopsy, PROCEDURE: Computed Tomography, DRUG: Ibrutinib, PROCEDURE: Positron Emission Tomography, BIOLOGICAL: Rituximab, DRUG: Venetoclax, DRUG: Zanubrutinib
Lymphoplasmacytic Lymphoma, Waldenstrom Macroglobulinemia
Placebo-Controlled Trial of IFx-Hu2.0 Followed By Pembrolizumab In Checkpoint Inhibitor Naïve Participants With Advanced Or Metastatic Merkel Cell Carcinoma
Amit Pande, MD - clinicaltrials@tuhurabio.com
NCT06947928
Inclusion Criteria:
• At least 18 years of age.
• Life expectancy equal to or greater than six months.
• Eastern Cooperative Oncology Group (ECOG) Performance Status \< 2.
• Must be recurrent and/or unresectable Stage III or Stage IV American Joint Committee on Cancer (AJCC) (8th edition) and have histologically confirmed Merkel cell carcinoma
• Must have at least one injectable lesion equal to or greater than 3 mm.
• Must have measurable disease as defined by RECIST v1.1.
• Participants should be CPI naïve i.e., no prior therapy with CPI including but not limited to Pembrolizumab, avelumab, ipilimumab, nivolumab.
• Tumor tissue from an archival core biopsy or resected site of disease must be provided for biomarker analyses. If archival tissue is not available, then a new biopsy should be performed.
• Adequate hematological, hepatic, and renal function according to laboratory ranges and medical criteria defined within the study protocol.
Exclusion Criteria:
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with protocol requirements.
• Participants with known active brain metastases with the exception of treated brain metastases that have imaging proving stability at least 4 weeks prior to the start of study treatment, no new metastases, and not requiring steroids.
• Participants with recurrent resectable MCC
• Participants with prior systemic chemotherapy
• Pregnant or breastfeeding females and females desiring to become pregnant or breastfeed within the timeframe of this study.
• Active, known, or suspected autoimmune disease. Potential Participants with type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll. Low-grade autoimmune toxicity is NOT an exclusion under this criterion.
• A condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids are permitted in the absence of active autoimmune disease.
DRUG: IFx-Hu2.0, DRUG: Placebo, DRUG: Pembrolizumab
Advanced Or Metastatic Merkel Cell Carcinoma
Merkel Cell Carcinoma, Advanced, Metastatic, MCC, pembrolizumab, Innate Immune Agonist, Skin Cancer, X-Mark, X Mark, Rare Skin Cancers
Study Adding Drugs to Usual Treatment for Large B-Cell Lymphoma That Returned or Did Not Respond to Treatment
Katarina Gasic - kgasic@swog.org
NCT05890352
Inclusion Criteria:
* Participants must have:
* Histologically confirmed relapsed/refractory LBCL as outlined by the World Health Organization (WHO) guidelines
* Follicular lymphoma, grade 3B
* Transformed lymphoma
* High grade B-cell lymphoma with or without MYC, BCL2 and/or BCL6 rearrangements
* Participants must have staging imaging performed within 28 days prior to registration, as follows. Positron emission tomography (PET)-computed tomography (CT) baseline scans are strongly preferred; diagnostic quality magnetic resonance imaging (MRI), contrast-enhanced CT, or contrast-enhanced MRI scans are also acceptable if PET-CT is not feasible at baseline. Note: PET-CT will be required at end of treatment (EOT) and progression for response assessment. All measurable lesions (longest diameter \>= 1.5 cm) must be assessed within 28 days prior to registration. Tests to assess non-measurable disease must be performed within 28 days prior to registration. All disease must be documented on the Baseline Tumor Assessment Form.
* Participants must have cell of origin (COO) determination of germinal center (GC)(GCB or non-GC GCB) of LBCL based on Hans immunohistochemistry algorithm (CD10, BCL6, MUM1) as noted on pathology report.
* Participants must have had 1-5 prior systemic treatment regimens including one systemic multiagent regimen for aggressive lymphoma
* Participants who have received prior systemic therapy must have completed their last treatment prior to registration. Participants must have recovered from previous therapy
* Steroid use for the control of non-Hodgkin lymphoma symptoms is allowable, but must be discontinued prior to Cycle 1, Day 1
* Participant must be \>= 18 years old
* Participant must have Zubrod Performance Status of 0-3
* Participant must have a complete medical history and physical exam within 28 days prior to registration
* Absolute neutrophil count \>= 1.0 x 10\^3/uL (within 28 days prior to registration)
* If there is documented lymphomatous involvement of the bone marrow as assessed by bone marrow biopsy within 90 days prior to registration, participants must have: Absolute neutrophil count (ANC) \>= 0.75 x 10\^3/uL
* Platelets \>= 75 x 10\^3/uL (within 28 days prior to registration)
* If there is documented lymphomatous involvement of the bone marrow as assessed by bone marrow biopsy within 90 days prior to registration, participants must have: Platelets \>= 50 x 10\^3/uL
* Aspartate aminotransferase (AST) =\< 3 x institutional upper limit of normal (IULN), alanine aminotransferase (ALT) =\< 3 x IULN (within 28 days prior to registration) unless due to Gilbert's disease, hemolysis, or lymphomatous involvement of liver.
* Participants with lymphomatous involvement of the liver must have AST =\< 5 x IULN, ALT =\< 5 x IULN
* Total bilirubin =\< 1.5 x IULN (within 28 days prior to registration) unless due to Gilbert's disease, hemolysis, or lymphomatous involvement of liver.
* Participants with lymphomatous involvement of the liver must have total bilirubin =\< 5 x IULN
* Participants must have a calculated creatinine clearance \>= 30 mL/min using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to registration
* Participants 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
* Participants must have recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) with the exception of alopecia
* Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at randomization and have undetectable viral load test 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 on the most recent test results obtained within the last year and received suppressive therapy
* Participants with a history of hepatitis C virus (HCV) infection must have an undetectable viral load. Participants currently being treated for HCV infection must have undetectable HCV viral load test on the most recent test results obtained within 28 days prior to registration
* Participants must be 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
* 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 the FACT-Lym and PRO-CTCAE forms in English or Spanish must agree to participate in the patient-reported outcome study
* 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.
Exclusion Criteria:
* Participants must not have active lymphomatous involvement of the central nervous system (CNS) because the treatments used in this study are not effective to sufficiently penetrate the blood brain barrier
* Participants must not have known abnormalities associated with myelodysplastic syndrome (MDS) (e.g., del 5q, chr 7 abn) and myeloproliferative neoplasms (MPN) (e.g., JAK2 V617F) observed in cytogenetic testing and deoxyribonucleic acid (DNA) sequencing. Testing is not required for eligibility determination
* Participants must not have a known prior history of T-cell lymphoblastic lymphoma (T-LBL)/T-cell acute leukemia (T-ALL). Testing is not required for eligibility determination
* Participants must not be a candidate based on investigator assessment to receive autologous stem cell transplant (ASCT) or must have declined ASCT. Participants who had disease progression after stem cell transplant or cellular therapy (such as chimeric antigen receptor (CAR) T-cell) are eligible
* Participants must not have received prior treatment with tafasitamab and/or lenalidomide
* Participants must not have had prior BTK inhibitor or tazemetostat
* Participants must not have any known allergy or reaction to any component of tafasitamab, lenalidomide, tazemetostat or zanubrutinib
* Participants must not be receiving direct vitamin K inhibitors or strong or moderate CYP3A inhibitors or inducers at the date of registration
* Notes: Because the list of these agents is constantly changing, it is important to regularly consult a frequently updated medical reference
* 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 and must follow the guidelines according to the lenalidomide Risk Evaluation and Mitigation Strategies (REMS) program. The effects of tazemetostat, zanubrutinib, lenalidomide and tafasitamab, and the combination of these drugs have not been studied on the developing human fetus are the effects are unknown. Individuals who are of reproductive potential must have agreed to use a highly 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, "acceptable 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 PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, DRUG: Lenalidomide, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Positron Emission Tomography, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration, BIOLOGICAL: Tafasitamab, DRUG: Tazemetostat, DRUG: Zanubrutinib
Grade 3b Follicular Lymphoma, High Grade B-Cell Lymphoma, High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements, Recurrent Diffuse Large B-Cell Lymphoma, Refractory Diffuse Large B-Cell Lymphoma, Transformed Non-Hodgkin Lymphoma
Personalized Antibody-Drug Conjugate Therapy Based on RNA and Protein Testing for the Treatment of Advanced or Metastatic Solid Tumors (The ADC MATCH Screening and Treatment Trial)
ctrrecruit@vcu.edu
NCT06311214
Inclusion Criteria:
* SCREENING PROTOCOL INCLUSION CRITERIA:
* Patients must have histologically confirmed solid tumor requiring therapy and meet one of the following criteria:
* Patients must have disease not amenable to curative-intent therapy AND
* Patients who have had disease progression after treatment with all available therapies for their disease that are known to confer benefit or are intolerant to such treatment will be eligible, if other eligibility criteria are met. If the patient is currently receiving therapy without progression, the clinician must have assessed that the current therapy is no longer benefitting the patient, or that the patient is not tolerating the therapy. Patients can be screened on ADC MATCH if they have had three or fewer-lines of chemotherapy in the advanced/metastatic setting and are expected to need a treatment change within 6 months, and ADC MATCH is felt to be appropriate next line therapy AND
* Patients with disease for which no standard treatment exists that has been shown to confer benefit OR
* Patients who are willing to forego standard therapies known to confer benefit
* NOTE: Patients can be on therapy at the time of initiating the Screening Protocol if the patient is interested in treatment on ADC MATCH upon progression, and the physician deems this appropriate
* Patient must have undergone RNA testing in a Clinical Laboratory Improvement Act (CLIA) environment or must submit archival tissue to determine RNA overexpression of ADC TOIs by the TARGET Assay. Patients who have high TOI RNA expression will have confirmation of TOI expression by CLIA IHC assay at MD Anderson Cancer Center (MDACC). Only patients with confirmed TOI protein expression will be eligible for assignment to a treatment cohort. Retrospective confirmation in another central laboratory may also be performed. (A proportion of specimens in patients who are negative for RNA overexpression may be tested to better understand the concordance between the TARGET Assay and immunohistochemistry (IHC) assays, as funding and tissue availability allows. Only patients with RNA and protein expression with be eligible for treatment on ADC MATCH)
* Patients must be willing to undergo mandatory pre-treatment and on-treatment tumor biopsies. Patients who do not consent to these research biopsies will not be eligible for prescreening. Patients who have screened and consented to a treatment cohort but are found to have disease that cannot be safely biopsied will be eligible for treatment provided all other eligibility criteria are met
* Patients must have measurable disease. (Per radiologic imaging within the past 2 months).
* Note: Patients with active metastatic disease that is not measurable but who are expected to be eligible for a Treatment Cohort can be screened after discussion with the primary investigator (PI)
* Age ≥ 18 years. Because no dosing or adverse event (AE) data are currently available on the use of the Cancer Therapy Evaluation Program (CTEP) investigational new drug (IND) agents to be used in the study in patients \< 18 years of age, children are excluded from this study
* Eastern Cooperative Oncology Group performance status of 0-2 based on most recent assessment (Karnofsky ≥ 50%)
* No history of transfusion dependence
* No history of persistent bone marrow suppression (absolute neutrophil count ≥ 1,500/mL and platelets ≥ 100,000/mL not attributable to active therapy; patients currently on bone marrow suppressive therapy can undergo assessment for the screening protocol but cannot be treated on any of the treatment cohorts unless bone marrow suppression is reversed off the suppressive therapy) (New testing will not be performed for the screening protocol, but rather existing labs will be assessed to assess eligibility)
* Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN). Documented Gilbert syndrome is allowed if total bilirubin is ≤ 3 × ULN (New testing will not be performed for the screening protocol, but rather existing labs will be assessed to assess eligibility)
* Aspartate transaminase (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine transaminase (serum glutamate pyruvate transaminase \[SGPT\]) ≤ 2.5 × institutional ULN. Transaminases up to 5 × ULN in the presence of liver metastases are not allowed to initiate the screening protocol but are allowed for the treatment cohorts (New testing will not be performed for the screening protocol, but rather existing labs will be assessed to assess eligibility)
* Creatinine ≤ institutional ULN OR glomerular filtration rate ≥ 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m\^2 (New testing will not be performed for the screening protocol, but rather existing labs will be assessed to assess eligibility)
* Patients must have albumin ≥ 3 g/dL
* 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 agents are eligible for this study
* 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 study, patients should be class 2B or better
* Women of childbearing potential must not be known to be pregnant. Pregnancy testing is not required
* Ability to understand and the willingness to sign a written informed consent document
* ADDITIONAL INCLUSION CRITERIA FOR TREATMENT COHORTS:
* Women of childbearing potential must have a negative serum pregnancy test result at treatment cohort screening
* The effects of the study drugs on the developing human fetus are unknown. For this reason and because investigational agents as well as 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 or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 months after completion of study drug administration (unless otherwise indicated in the eligibility section \[Section 2\] of the Treatment Cohort protocols). 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 study entry, for the duration of study participation, and for 6 months after completion of study drug administration
* Hemoglobin \> 9.0 g/dL
* Leukocytes ≥ 3000/mL
* Absolute neutrophil count ≥ 1,500/mL
* Platelets ≥ 100,000/mL
* Patient must be willing to sign the relevant treatment cohort consent form
* Patients should have received no more than 3 prior lines of chemotherapy in the advanced/metastatic setting. Therapy given for only 1 cycle and discontinued because of toxicity in the absence of disease progression will not be counted as a line of therapy. Radio-sensitizing chemotherapy, if only given with radiation therapy will not be considered a line of therapy
* Human immunodeficiency virus-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this study
* 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
* COHORT A INCLUSION CRITERIA:
* Patients must fulfill all the eligibility criteria outlined in the ADC MATCH screening protocol at the time of treatment cohort A registration
* Patient must have high Trop-2 protein expression (IHC 2+ or 3+) as determined by the MD Anderson Cancer Center Clinical Laboratory Improvement Amendments IHC assay
* Patients who have Trop-2 IHC testing without RNA testing or who have Trop-2 IHC 2 or 3+ expression but do not have Trop-2 expression detected on RNA testing will not be eligible for the trial.
* Patients who have Trop-2 RNA expression and Trop-2 IHC 2+ or 3+ on another Trop-2 IHC test will undergo Trop-2 testing with the integral MDACC IHC assay
* Patients who already have RNA expression testing demonstrating Trop-2 RNA expression as well as IHC testing on the MDACC CLIA lab platform will be eligible for enrollment after review of results by the Precision Oncology Decision Support team without having to repeat Trop-2 IHC results as part of pre-screening. Patients who have had TROP2 2+ testing result performed outside of MDACC will have to undergo MDACC TROP2 IHC analysis before enrollment
* COHORT B INCLUSION CRITERIA:
* Patients must fulfill all the eligibility criteria outlined in the ADC MATCH screening protocol at the time of treatment cohort B registration
* Patient must have high Nectin-4 protein expression (IHC 2+ or 3+) as determined by the MD Anderson Cancer Center Clinical Laboratory Improvement Amendments IHC assay
* COHORT C INCLUSION CRITERIA:
* Patients must fulfill all the eligibility criteria outlined in the ADC MATCH screening protocol at the time of treatment cohort C registration
* Patient must have HER2 protein expression (IHC 2+ or 3+) as determined by the MD Anderson Cancer Center (MDACC) IHC assay
* Patients who have HER2 IHC testing without RNA testing or who have HER2 IHC 2 or 3+ expression but do not have HER2 expression detected on RNA testing will not be eligible for the trial
* Patients who have HER2 RNA expression and HER2 IHC 3+ or 2+ on another HER2 IHC test will undergo HER2 testing with the integral MDACC IHC assay
* Patients who already have RNA expression testing demonstrating HER2 RNA expression as well as IHC testing on the MDACC CLIA lab platform will be eligible for enrollment after review of results by the Precision Oncology Decision Support team without having to repeat HER2 IHC results as part of pre-screening. Patients who have had HER2 2+ testing result performed outside of MDACC will have to undergo MDACC HER2 IHC analysis before enrollment
* Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 7 months after completion of study drug administration. Women should not breastfeed during the study treatment period and for 7 months after completion of study drug administration. 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 study entry, for the duration of study participation, and for 4 months after completion of study drug administration. Female patients must not donate, or retrieve for their own use, ova from the time of screening throughout the study treatment period and for at least 7 months after the final study drug administration. Female patients may wish to consider preservation of ova prior to enrollment in the study. Male patients should refrain from freezing or donating sperm during the study and for 6 months after the final study drug administration. Preservation of sperm should be considered prior to enrollment in the study
* LVEF ≥50% within 28 days before enrollment
Exclusion Criteria:
* SCREENING PROTOCOL EXCLUSION CRITERIA:
* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease. Patients with treated brain metastases are eligible if follow-up brain imaging 4 weeks after central nervous system-directed therapy shows no evidence of progression
* Clinically significant cardiovascular condition including: (1) history of congestive heart failure (New York Health Association class \> 2), (2) any history of unstable angina, (3) myocardial infraction within the past 12 months, or (4) any history of supraventricular arrhythmia or ventricular arrhythmia requiring treatment or intervention within the past 12 months
* History or presence of abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful
* Active or chronic corneal disorder including, but not limited to, Sjogren's syndrome, Fuchs corneal dystrophy (requiring treatment), history of corneal transplantation, active herpetic keratitis, and/or active ocular conditions requiring ongoing treatment/monitoring such as wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, presence of papilledema, and acquired monocular vision
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to the ADCs used in the study
* History of interstitial lung disease or pneumonitis requiring steroid therapy
* Grade 2 or greater peripheral neuropathy
* Patients requiring the use of full dose coumarin-derivative anticoagulants such as warfarin. Low molecular weight heparin is permitted for prophylactic or therapeutic use. Factor X inhibitors are permitted
* Note: Warfarin may not be started while enrolled in the treatment cohorts. Stopping the anticoagulation for biopsy should be per site standard operating practice
* Pregnant women are excluded from the study because the study drugs are investigational or approved agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with any of the study drugs, breastfeeding should be discontinued if the mother is treated with any of the study drug
* ADDITIONAL EXCLUSION CRITERIA FOR TREATMENT COHORTS:
* Patients must have adequate washout from prior therapy at the time of study treatment initiation: 4 weeks from major surgery; 4 weeks from antibody-based therapy; 2 weeks or 5 half-lives (whichever is shorter) from any targeted therapy or small molecule therapy; 3 weeks or 5 half-lives (whichever is shorter) from chemotherapy or 6 weeks in the case of certain therapies (e.g., extensive radiotherapy, mitomycin C, and nitrosoureas); and 4 weeks from radiation therapy. Patients should have received no more than 3 prior lines of chemotherapy. Testosterone suppression as supportive treatment for castration-resistant prostate cancer and ovarian suppression in premenopausal patients with breast cancer that have supportive treatment and not anticancer treatment role (with luteinizing hormone-releasing hormone analogs) will be allowed if the patients were on these supportive treatments before starting the study. Use of bone-modifying medications (bisphosphonates or denosumab) will be allowed. Palliative radiotherapy of non-target lesions is permitted, but presence of new or worsening metastases will be considered progressive disease. If there is clear evidence of clinical benefit, study treatment may be continued 2 weeks after completion of palliative radiotherapy to lesions that are non-target lesions. Patients can be on therapy during treatment cohort screening
* Patients who are currently receiving any other investigational agent(s)
* Received systemic therapy with corticosteroids at \> 20 mg/day prednisone or equivalent within 1 week prior to cycle 1 day 1
* Patients who have not recovered from AEs due to prior anticancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia
* When the corrected QT interval (QTc) by Fridericia's formula is \< 120 ms, \> 450 ms in males and \> 470 ms in females. When the QTc by Rautaharju's formula is ≥ 120 ms, \> 450 ms in males and \> 470 ms in females
* Uncontrolled infection requiring intravenous antibiotic, antiviral, or antifungal use
* Received a live, attenuated vaccine within 30 days prior to cycle 1 day 1. Enrolled patients should not receive live vaccine during the study. Non-live COVID vaccines will be allowed on study, but it is recommended to avoid their use during the first treatment cycle (from 3 days prior to cycle 1 day 1 through cycle 2 day 3)
* Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Other concurrent medical or psychiatric conditions that, in the investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations
* COHORT A EXCLUSION CRITERIA:
* Patients with histologically documented advanced colorectal cancer, urothelial cancer, head and neck cancer (Note: exceptions include patients with adenoid cystic cancer, salivary gland cancer, thyroid cancer, and parathyroid cancer, who are eligible), triple negative breast cancer (TNBC), HR-positive breast cancer, HER2-positive breast cancer, small cell lung cancer, NSCLC, and endometrial cancer
* Note: Patients with cancer of unknown primary are allowed
* Patients who have received growth factor support within 2 weeks of study treatment initiation
* Coadministration of sacituzumab govitecan-hziy(IMMU-132) with inhibitors of UGT1A1 may increase systemic exposure to the active metabolite, SN-38. UGT1A1 inhibitors should not be administered concomitantly with sacituzumab govitecan-hziy (IMMU-132) unless there are no therapeutic alternatives
* Prior topoisomerase 1 inhibitor treatment
* Prior treatment with a Trop-2-targeting ADC
* Has active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or gastrointestinal (GI) perforation within 6 months of treatment cohort A registration
* COHORT B EXCLUSION CRITERIA:
* Patients with histologically documented advanced urothelial cancer, head and neck cancer (to include salivary gland cancer and adenoid cystic cancer), breast cancer, lung cancer, gastric cancer, gastroesophageal junction cancer, esophageal cancer, prostate cancer, or penile cancer
* Note: Patients with cancer of unknown primary are allowed
* Concomitant use of strong inhibitors or strong inducers of cytochrome P450 (CYP)3A4. Washout period is 2 weeks prior to study treatment initiation
* History of uncontrolled diabetes mellitus within 3 months before the first dose of study treatment. Uncontrolled diabetes mellitus is defined as hemoglobin A1c ≥ 8% or hemoglobin A1c between 7 and \< 8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained
* Known active keratitis or corneal ulcerations. Patients with superficial punctate keratitis are allowed if the disorder is being adequately treated
* Known hypersensitivity to enfortumab vedotin or to any excipient in the drug formulation of enfortumab vedotin (including histidine, trehalose dihydrate, and polysorbate 20), or known hypersensitivity to biopharmaceutical produced in Chinese hamster ovary cells
* Prior treatment with an ADC with vedotin payload
* COHORT C EXCLUSION CRITERIA:
* Patients with histologically documented advanced breast cancer, non-small cell lung cancer (NSCLC), colorectal carcinoma (CRC), gastric cancer, or gastroesophageal junction (GEJ) cancer
* Note: Patients with cancer of unknown primary are allowed
* Previous treatment with topoisomerase I inhibitors as a free form or as other formulations
* Prior PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, PROCEDURE: Echocardiography Test, OTHER: Electronic Health Record Review, DRUG: Enfortumab Vedotin, OTHER: Immunohistochemistry Staining Method, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Multigated Acquisition Scan, BIOLOGICAL: Sacituzumab Govitecan, BIOLOGICAL: Trastuzumab Deruxtecan
Advanced Malignant Solid Neoplasm, Metastatic Malignant Solid Neoplasm
The Multicenter Stress Cardiac Magnetic Resonance Quantitative Perfusion Imaging in the United States Study (SPINS2)
Raymond Y Kwong, MD, MPH - rykwong@bwh.harvard.edu
NCT06854458
Inclusion Criteria:
• male or female at age 35-85 years,
• presence of either of the following sign/symptom that led to a referral to stress cardiac magnetic resonance imaging:
• chest pain or anginal equivalent, or
• abnormal electrocardiogram with a suspicion of coronary artery disease
• Intermediate or high risk of significant coronary disease based on at least 1 of the following conditions: a) patient age \> 45 for male, 50 for female b) Diabetes, hypertension, or hypercholesterolemia: by either history or medical treatment c) family history of premature coronary disease: first degree relative at age \<= 55 male and \<=65 female d) history of smoking of \> 10 packed-years e) post-menopausal state \>5 years f) any chronic inflammatory conditions d) Body mass index \> 30 e) Any medical documentation of coronary or peripheral artery disease
Exclusion Criteria:
• Acute myocardial infarction within the past 30 days prior to cardiac magnetic resonance imaging
• Confirmed diagnosis of any significant non-coronary cardiac conditions below:
• any severe-grade valvular heart disease,
• left ventricular ejection fraction \<40% from any known non-coronary causes,
• infiltrative cardiomyopathy,
• hypertrophic cardiomyopathy,
• pericardial disease with significant constriction, or
• active pregnancy,
• any competing conditions leading to an expected survival of \< 2 years
• contraindication to vasodilator (regadenoson or adenosine)
• metallic device or object that poses an magnetic resonance imaging safety hazard
• metallic device with a high likelihood of non-diagnostic cardiac magnetic resonance images
DIAGNOSTIC_TEST: Quantitative Myocardial Blood Flow Evaluation, DIAGNOSTIC_TEST: Qualitative Myocardial Blood Flow Evaluation, DRUG: Gadavist, DRUG: Vasodilator, DIAGNOSTIC_TEST: Blood draw for the laboratory assessment
Ischemic Heart Disease (IHD), Cardiac Magnetic Resonance Imaging, Myocardial Blood Flow
Myocardial Blood Flow, Cardiac Magnetic Resonance, Quantitative perfusion, Cardiovascular Outcomes
US National OCS Heart Perfusion (OHP) Registry
Raicca Haqqi - rhaqqi@transmedics.com
NCT05915299
Inclusion Criteria:
* N/A
Exclusion Criteria:
* N/A DEVICE: OCS Heart
Heart Transplant
C-SMART vs BE Well for Patients With Brain Tumors
Sarah Braun, Ph.D - sarah.braun@vcuhealth.org
NCT07224503
Patient
Inclusion Criteria:
* Patient of Virginia Commonwealth University Neuro-Oncology clinic
* Confirmed primary brain tumor diagnosis by histology or neuro-oncologist review of imaging
* At least one domain of neurocognitive function \>1.5 SD below the average or the individual's estimated premorbid functioning, using the expanded International Cognition and Cancer Task Force (ICCTF) clinical trials battery and Test of Premorbid Functioning62 for comparison; (3) \>1 month post brain surgery and/or radiation therapy, if applicable;
* Estimated premorbid intelligence \>75.
* Patients must be age 18+ and
* Primarily English speaking.
Patient Exclusion Criteria:
* Presence of major neurocognitive impairment that would prevent participation in the intervention, and/or severe aphasia, and/or inability to understand and provide informed consent
* Inability to attend weekly telehealth appointments
* Clinically significant insomnia symptoms coupled with report that insomnia is more interfering than cognitive symptoms
* \< 1 month post brain surgery and/or radiation therapy
* Unstable internet connection or an inability to work teleconferencing software. Participants will be supplied an iPad if they do not have an adequate device.
* Participants cannot have metal in their body as the MRI scan could cause them harm
* If female of childbearing years, they cannot be pregnant as the MRI scan may pose risk to the unborn fetus
Caregiver Inclusion Criteria
* Must enroll with a patient (see criteria above)
* Must be age 18+ and
* Primarily English speaking
Caregiver Exclusion Criteria
-N/A BEHAVIORAL: C-SMART, BEHAVIORAL: BE Well
Brain Tumor
Shorter Chemo-Immunotherapy Without Anthracycline Drugs for Early-Stage Triple Negative Breast Cancer
Alicia Aranda - aaranda@swog.org
NCT05929768
Inclusion Criteria:
* Participants must have histologically confirmed estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative breast cancer (TNBC) defined as ER \< 5%, PR \< 5%, and HER2 negative (per 2020 American Society of Clinical Oncology \[ASCO\] College of American Pathologists \[CAP\] guidelines)
* NOTE: Participants with weakly ER or PR positive disease, defined as ER and/or PR between 1-4% by immunohistochemistry, are eligible if adjuvant endocrine therapy is not recommended/planned by the treating physician
* Participants must have American Joint Committee on Cancer (AJCC) 8 anatomic tumor clinical stage either
* T2-T4, N0, M0 or
* T1-T3, N1-2, M0
* Note: All participants with clinically suspicious nodes must undergo core needle biopsy or fine needle biopsy per standard clinical practice to pathologically confirm nodal status
* Participants must have breast and axillary imaging with mammogram and/or ultrasound and/or magnetic resonance imaging (MRI) within 49 days prior to randomization
* Note: Participants with bilateral invasive breast cancer are eligible if both breast cancers are ER-negative, PR-negative, and HER2-negative provided they meet the other eligibility criteria
* Participants must not have T4/N+, any N3, or inflammatory breast cancer
* Participants must not have metastatic disease (M1)
* Participants must not have received prior systemic therapy or radiation therapy with curative intent for the current breast cancer
* Participants must not have had previous definitive ipsilateral breast surgery for the current breast cancer
* Participants must not have current or anticipated use of other investigational agents while participating in this study
* Participants must not have history of allergic reactions attributed to compounds of similar chemical or biologic composition as study agents
* Participants must not have severe hypersensitivity (\>= grade 3) to pembrolizumab or any of its excipients
* Participants must not have received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137)
* Participants must not be currently participating in or have participated in a study of an investigational agent or used an investigational device within 28 days prior to randomization
* Participants must be \>= 18 years old
* Participants must have Zubrod performance status of 0-2
* Participants with evidence of peripheral neuropathy must have it at =\< grade 1, by Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 5.0, within 28 days prior to randomization
* Participants must have a complete medical history and physical exam within 28 days prior to randomization
* Hemoglobin \>= 9.0 g/dL or \>= 5.6 mol/L (within 28 days prior to randomization)
* (Criteria must be met without erythropoietin dependency and without packed red blood cell transfusion within last 2 weeks)
* Leukocytes \>= 3 x 10\^3/uL (within 28 days prior to randomization)
* Absolute neutrophil count \>= 1.5 x 10\^3/uL (within 28 days prior to randomization)
* Platelets \>= 100 x 10\^3/uL (within 28 days prior to randomization)
* Total bilirubin =\< 1.5 x institutional upper limit of normal (IULN), OR direct bilirubin =\< IULN for participants with total bilirubin \> 1.5 x IULN (unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin =\< 5 x institutional IULN) (within 28 days prior to randomization)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 x institutional upper limit of normal (ULN) (within 28 days prior to randomization)
* Participants must have a serum creatinine =\< the IULN OR calculated creatinine clearance \>= 50 mL/min/1.73m\^2 using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to registration
* Participants must have adequate cardiac function. Participants must have left ventricular ejection fraction \>= 50% as assessed by either echocardiography (ECHO) or multigated acquisition scan (MUGA) assessed within 28 days prior to registration. 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 and must be class 2B or better
* Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at randomization and have undetectable viral load test on the most recent test results obtained within 6 months prior to randomization
* 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 randomization, if indicated
* Note: No testing for Hepatitis B is required unless mandated by local health authority
* 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 test on the most recent test results obtained within 6 months prior to randomization, if indicated
* Note: No testing for hepatitis C is required unless mandated by local health authority
* Participants with history of diabetes must not have uncontrolled diabetes in the opinion of the treating investigator
* Participants must not have uncontrolled hypertension in the opinion of the treating investigator
* Participants must not have had a major surgery within 14 days prior to randomization. Participants must have fully recovered from the effects of prior major surgery in the opinion of the treating investigator
* Participants must not have severe or active infections within 14 days prior to Randomization, including but not limited to hospitalization for infection, bacteremia, or severe pneumonia
* Participants must not have a diagnosis of immunodeficiency and be receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to randomization
* Participants must not have active autoimmune disease that has required systemic treatment in 2 years prior to randomization (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment
* Participants must not have a history of (non-infectious) pneumonitis that required steroids, or has current (non-infectious) pneumonitis
* Participants must not have received a live vaccine within 30 days prior to randomization. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist \[registered trademark\]) are live attenuated vaccines and are not allowed
* 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 treatment regimen
* Participants must not be pregnant or nursing. 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 have one (1) physical 4-5-micron single hematoxylin and eosin (H\&E) slide from the archival pretreatment diagnostic biopsy available for submission
* 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 questionnaires in English, Spanish, or French must be offered the opportunity to participate in the Patient-Reported Outcome study
* NOTE: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
* 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
* As part of the registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system PROCEDURE: Biospecimen Collection, DRUG: Carboplatin, DRUG: Cyclophosphamide, DRUG: Docetaxel, DRUG: Doxorubicin, DRUG: Paclitaxel, BIOLOGICAL: Pembrolizumab, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration, PROCEDURE: Surgical Procedure
Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8, Anatomic Stage IIIB Breast Cancer AJCC v8, Early Stage Triple-Negative Breast Carcinoma
A Study to Investigate the Efficacy and Safety of Bemdaneprocel in Adults Who Have Parkinson's Disease (exPDite-2)
Patient Engagement - clinicaltrials@bluerocktx.com
NCT06944522
Inclusion Criteria:
* Diagnosis of clinically established PD as defined by the International Parkinson and Movement Disorders Society
* Individual of any sex ≥45 to ≤75 years of age at informed consent
* Robust and clear response to DA therapy as defined by MDS-UPDRS Part III
* ≥4 and \<12 years from time of PD diagnosis at informed consent
* Must demonstrate responsiveness to levodopa therapy
* Receiving medical therapy for the treatment of PD symptoms
* ≥2.5 hours of daily OFF-time
* Vaccinated per current national guidelines or local practice for patients with altered immunocompetence
Exclusion Criteria:
* PD presenting with recurrent falls
* Diagnosis of primary mitochondrial disorder, epilepsy, stroke, multiple sclerosis, or clinical features suggestive of a neurodegenerative disease other than PD, including multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, or Lewy body dementia
* Any current or relevant previous history of serious, severe, or unstable physical, neurological, or psychiatric illness that may interfere with study participation, participant's safety, or assessment of endpoints per investigator's judgment
* History of gene therapy or cell therapy
* Prior treatment with intrajejunal or subcutaneous infusion therapies for PD
* Prior surgical or radiation therapy to the brain, including deep brain stimulation (DBS) and lesion therapy, or prior history of intradural spinal cord surgery
* Contraindication to surgery, general anesthesia, cell therapy, immunosuppression, or other required drugs, or anything that prevents use of PET or MRI
* Any active infection (including but not limited to HIV, HCV, HBV, CMV, syphilis, or tuberculosis) or condition that, in the opinion of the investigator could put the participant at significant risk from immunosuppression or impact the participant's ability to perform study assessments
* Current or previously active malignant disease within the past 5 years
* Chronic immunosuppressive therapy
* Receipt of another investigational therapy within 5 half-lives of the active treatment
* Pregnancy or breastfeeding BIOLOGICAL: bemdaneprocel, PROCEDURE: Sham surgery
Parkinsons Disease (PD)
exPDite-2, Cell Therapy, Cellular Therapy, Dopaminergic Neuronal Cell Therapy, Parkinsons Disease