Tazemetostat and Venetoclax in Relapsed/Refractory Non-Hodgkin Lymphoma

Launched by WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY · Nov 15, 2022

Keywords

ClinConnect Summary

This clinical trial is studying the combination of two medications, tazemetostat and venetoclax, to see how they work together in treating patients with relapsed or refractory Non-Hodgkin Lymphoma, specifically types like Follicular Lymphoma and Diffuse Large B Cell Lymphoma. The researchers want to find out the best dose of venetoclax to use with tazemetostat, what side effects might occur, and how effective this combination is in fighting the cancer. Participants will take the medications in pill form daily and will need to visit the clinic regularly for blood tests and scans to monitor their health and the progress of their cancer.

To be eligible for this study, participants must have a confirmed diagnosis of Follicular Lymphoma or Diffuse Large B Cell Lymphoma, and they should have already received at least one treatment that hasn’t worked. The trial is open to both men and women aged 65 and older. Participants may receive the study medications for up to 24 months. It’s important to note that there are certain health conditions and recent medical events that could prevent someone from joining the trial, such as significant heart problems or recent surgeries. Overall, this trial aims to explore a new treatment option for patients who have not responded to previous therapies.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• Patients must meet the following criteria for study entry:
• • 1. Adults aged ≥18
• • 2. Require therapy as determined by the treating physician
• 3. Patients must have adequate organ and bone marrow function:
• • Absolute neutrophil count (ANC) ≥ 1 x 109/L without growth factor support (filgrastim or pegfilgrastim) for at least 14 days
• • Platelet count ≥75 x 109/L, evaluated at least 7 days after last platelet transfusion
• • Hemoglobin ≥9.0g/dL, independent of transfusion
• • Total bilirubin \< 1.5 x's the upper limit of the normal range (ULN), except Gilbert's disease
• • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 3 x's ULN.
• • Calculated creatinine clearance according to the Cockcroft-Gault equation. ≥ 40 mL/min
• • 4. ECOG PS 0-2
• • 5. Ability and willingness to provide signed Informed Consent Form
• • 6. Ability and willingness to comply with the requirements of the study protocol
• • 7. Measurable disease (defined as ≥ 1.5cm in diameter) In addition, patients must meet the following conditions for enrollment based on whether they have DLBCL or FL.
• R/R DLBCL Cohort:
• • 1. Histologically confirmed, biopsy-proven diagnosis of DLBCL (as determined by WHO standard classification criteria).
• • Please note: Transformed DLBCL patients are eligible, with the exception of Richter's transformation.
• • 2. Subjects must have received at least two prior lines of therapy for lymphoma with evidence of disease progression.
• • 3. Subjects are eligible if they have progressed after ASCT OR if they are ineligible for ASCT, as determined by their treating physician.
• R/R FL Cohort:
• • 1. Histologically confirmed, biopsy-proven diagnosis of FL
• • 2. Subjects are eligible if they have progressed after two or more lines of therapy for lymphoma or have no satisfactory treatment alternatives
• Exclusion Criteria:
• Patients who meet any of the following criteria will be excluded from study entry:
• • 1. Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months of the first dose of study drug; or cardiac ventricular arrhythmia.
• • 2. Known hypersensitivity to any of the study drugs
• • 3. History of other malignancy that could affect compliance with the protocol or interpretation of results
• • a. Patients with a history of curatively treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix are generally eligible. Patients with a malignancy that has been treated, but not with curative intent, will also be excluded, unless the malignancy has been in remission without treatment for 2 years prior to enrollment.
• • 4. Known CNS involvement at diagnosis (CNS evaluation not required in the absence of clinical suspicion)
• • 5. Richter's transformation from CLL
• • 6. Evidence of other clinically significant uncontrolled condition(s) including, but not limited to, uncontrolled systemic infection (viral, bacterial, or fungal).
• • 7. Major surgery within 3 weeks prior to the start of study treatment
• • 8. Venous thrombosis or pulmonary embolism within the last 3 months before starting study; whereas subjects greater than 3 months since deep vein thrombosis/pulmonary embolism are eligible but are recommended to receive prophylaxis.
• • 9. Uncontrolled infection with human immunodeficiency virus (HIV) or human T-cell leukemia virus 1
• • 10. Pregnant or lactating
• • 11. Patients capable of becoming pregnant or getting someone else pregnant must be willing to use highly effective birth control as described in Section 4.4
• 12. Malabsorption syndrome or other condition that precludes enteral route of administration Patients who meet any of the following criteria will be excluded from study entry:
• • 13. Inability to swallow tablets
• • 14. Known allergy to both xanthine oxidase inhibitors and rasburicase
• • 15. Clinically significant history of liver disease, including but not limited to viral or other hepatitis, current alcohol abuse, or cirrhosis Note: Subjects with positive HBV core antibody or surface antigen are eligible as long as they have an undetectable HBV DNA PCR and are willing to undergo monthly DNA testing, and receive concurrent antiviral therapy with entecavir, tenofovir, or lamivudine, and continued for a minimum of 6 months after completion of therapy.
• • 16. Active hepatitis C (defined as a positive HCV viral load)
• • 17. Chronic use of moderate or strong CYP3A4 modulators (inhibitor or inducer) or any other prohibited medications. A washout period of 5 half-lives or 14 days, whichever is longer, is required prior to venetoclax or tazemetostat dosing if a prohibited medication is discontinued.
• • 18. Chronic use of a P-gp inhibitor, or a P-gp substrate with a narrow therapeutic index (see Section 7.8). A washout period of 5 half-lives or 14 days, whichever is longer is required prior to venetoclax or tazemetostat dosing if a prohibited medication is discontinued.
• • 19. Prior exposure to either tazemetostat or venetoclax
• • 20. Has a prior history of T-LBL/T-ALL
• • 21. Subjects who have undergone a solid organ transplant
• • 22. Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the subject's participation in this study OR interfere with their ability to receive study treatment or complete the study.
• • 23. Requires the use of warfarin (because of potential drug-drug interactions that may potentially increase the exposure of warfarin)
• • 24. Vaccination with live vaccines within 28 days prior to treatment
• • 25. Consumed grapefruit or grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit within 3 days prior to the first dose of study drug