An Early Phase Study of Venetoclax, Lenalidomide, and Rituximab/Hyaluronidase in Slow-Growing Lymphomas That Have Come Back After Treatment or Have Not Responded to Treatment (NCT04447716)

Usually NOT eligible if any of the following apply:

• Exclusion Criteria: Known hypersensitivity to any of the study drugs study drugs
• Known central nervous system (CNS) involvement by lymphoma
• Prior allogeneic stem cell transplant is not permitted if patient is fewer than 4 months from transplant and has either active graft versus host disease or on immunosuppression
• History of severe allergic reactions to humanized monoclonal antibodies
• Prior use of lenalidomide or venetoclax or other BCL2 family inhibitors; prior rituximab is allowed as long as they continue to express CD20 and are not rituximab refractory as defined as: \* Did not respond (at least a partial response \[PR\]) to rituximab or rituximab (R)-chemoregimen therapy \* Time to disease progression \< 6 months after last rituximab dose
• History of other malignancy that could affect compliance with the protocol or interpretation of results \* Patients with a history of curatively treated basal or squamous cell carcinoma or stage 1 melanoma of the skin or in situ carcinoma of the cervix are eligible \* Patients with a malignancy that has been treated with surgery alone with curative intent will also be excluded. Individuals in documented remission without treatment for \>= 2 years prior to enrollment may be included at the discretion of the investigator
• Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results or that could increase risk to the patient, including renal disease that would preclude chemotherapy administration or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)
• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) 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) within 4 weeks prior to registration
• Requires the use of warfarin (because of potential drug-drug interactions that may potentially increase the exposure of warfarin)
• Received the following agents within 7 days prior to registration: \* Steroid therapy for anti-neoplastic intent \* Strong and moderate CYP3A inhibitors \* Strong and moderate CYP3A inducers \* Consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit within 3 days prior to the first dose of venetoclax
• Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis Presence of positive test results for hepatitis B virus (HBV), hepatitis B surface antigen (HBsAg), or hepatitis C (HCV) antibody \* Patients who are positive for HCV antibody must be negative for HCV by polymerase chain reaction (PCR) to be eligible for study participation \* Patients with occult or prior HBV infection (defined as positive total hepatitis B core antibody \[HBcAb\] and negative HBsAg) may be included if HBV deoxyribonucleic acid (DNA) is undetectable. These patients must be willing to undergo monthly DNA testing.
• Known infection with human immunodeficiency virus (HIV) or human T-cell leukemia virus 1 (HTLV-1)