Tazemetostat and Venetoclax in Relapsed/Refractory Non-Hodgkin Lymphoma

The goal of this clinical trial is to learn about how a combination of tazemetostat and venetoclax in people with relapsed/refractory Non-Hodgkin Lymphoma (R/R NHL). The main questions that this trial aims to answer are what is the best dose of venetoclax to give with tazemetostat to people with R/R NHL; what types of side effects do people with R/R NHL get when taking venetoclax with tazemetostat; and what effects does this combination have on R/R NHL. Participants will need to take pills by mouth every day and regularly come to the clinic for blood work and imagining to monitor side effects and cancer progression. Participants may receive study drugs for up to 24 months.

Inclusion Criteria:Histologically confirmed, biopsy-proven diagnosis of FL or DLBCL.Subjects must have been treated with at least one prior line of therapy for lymphoma with evidence of disease progression.Subjects are eligible if they have progressed after ASCT OR if they are ineligible for ASCTExclusion Criteria:Significant cardiovascular impairment, such as history of congestive heart failure, uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months of the first dose of study drugKnown hypersensitivity to any of the study drugsHistory of other cancer (some exceptions apply)Known CNS (brain or spinal cord) involvement at diagnosisRichter's transformation from CLLEvidence of uncontrolled systemic infection (viral, bacterial, or fungal)Major surgery within 3 weeks prior to the start of study treatmentVenous thrombosis or pulmonary embolism within the last 3 months before starting studyUncontrolled infection with human immunodeficiency virus (HIV) or human T-cell leukemia virus 1Pregnant or lactating (people capable of becoming pregnant or getting someone else pregnant must be willing to use highly effective birth control)Malabsorption syndrome or other condition that precludes enteral route of administrationInability to swallow tabletsKnown allergy to both xanthine oxidase inhibitors and rasburicaseClinically significant history of liver disease, including but not limited to viral or other hepatitis, current alcohol abuse, or cirrhosisActive hepatitis C (defined as a positive HCV viral load)Chronic use of moderate or strong CYP3A4 modulators (inhibitor or inducer); chronic use of a P-gp inhibitor, or a P-gp substrate with a narrow therapeutic index; or use of certain other prohibited medicationsPrior exposure to either tazemetostat or venetoclaxPrior history of T-LBL/T-ALLPrevious solid organ transplantRequires the use of warfarin (because of potential drug-drug interactions that may potentially increase the exposure of warfarin)Vaccination with live vaccines within 28 days prior to treatmentConsumed 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