Phase II Venetoclax, Obinutuzumab and Bendamustine in High Tumor Burden Follicular Lymphoma as Front Line Therapy

Inclusion Criteria

• - Patient must have a histologically confirmed (biopsy-proven) diagnosis of follicular B-cell non-Hodgkin lymphoma (WHO classification: follicular center grades 1, 2, and 3a [3b patients are not eligible]), with no evidence of transformation to large cell histology. - Patient must meet criteria for High Tumor Burden (higher risk) as defined by either the Groupe D'Etude des Lymphomes Follicularies (GELF) criteria [at least one criterion] OR the follicular lymphoma international prognostic index (FLIPI) [score of 3, 4, or 5]. - Patient must have Stage II, III or IV disease. - Baseline measurements and evaluations (PET/ CT) must be obtained within 10 weeks of randomization to the study. Patient must have at least one objective measurable disease parameter. - Age ≥ 18 years. - Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. - Ability to understand and willingness to sign Institutional Review Board (IRB)-approved informed consent. - Willing to provide mandatory tissue samples (if sufficient tissue available) for research purposes. - Adequate organ function as measured by the following criteria: - Absolute Neutrophil Count (ANC) ≥ 1000/mm³ - Hemoglobin ≥ 8 g/dL - Platelets ˃75,000/mm³ - Creatinine clearance ≥ 50 mL/min, calculated with the use of 24-hour creatinine clearance or by Cockcroft-Gault formula - Total Bilirubin ≤ 1.5x Upper Limit of Normal (ULN) or ≤ 3x ULN for patients with documented Gilbert's syndrome - Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) ≤ 2.5x ULN - Alkaline Phosphatase <5x ULN - All females of childbearing potential (not surgically sterilized and between menarche and 1 year post menopause) must have a blood or urine test to rule out pregnancy within 2 weeks prior to registration. - Women must not be pregnant or breastfeeding. - Patient must have had no prior chemotherapy, radiotherapy or immunotherapy for lymphoma. For purposes of this trial, prednisone or other corticosteroids used for non-lymphomatous conditions will not be considered as prior chemotherapy. In addition, a prior/recent short course (<2 weeks) of steroids for symptom relief of lymphoma-related symptoms will not make a patient ineligible. - Patient must have no recent history of malignancy except for adequately treated basal cell or squamous cell skin cancer, Stage I melanoma of the skin, or in situ cervical cancer. Individuals in documented remission without treatment for ≥ 2 years prior to enrollment may be included at the discretion of the investigator. - Patient must have no active, uncontrolled infections. - Patients must be tested for hepatitis B virus (HBV), hepatitis B surface antigen (HBsAg+) and hepatitis C (HCV) antibody within 6 weeks of registration. Patients who are chronic carriers of HBV with positive HBsAg+ and positive HCV serology are excluded, as chemotherapy and B-cell depleting therapy have been associated with virus reactivation and fulminant hepatitis. NOTE: Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) may be included if HBV DNA is undetectable. If enrolled, patients must be willing to undergo monthly HBV DNA testing. Patients with positive HCV antibody must be negative for HCV by polymerase chain reaction (PCR) to be eligible for study participation. - HIV positive patients are not excluded, but to enroll, must meet all of the below criteria: - HIV is sensitive to antiretroviral therapy. - Must be willing to take effective antiretroviral therapy if indicated. - No history of CD4 prior to or at the time of lymphoma diagnosis <300 cells/mm³. - No history of AIDS-defining conditions. - If on antiretroviral therapy, must not be taking zidovudine or stavudine. - Must be willing to take prophylaxis for Pneumocystis jiroveci pneumonia during therapy and until at least 2 months following the completion of therapy or until the CD4 cells recover to over 250 cells/mm³, whichever occurs later. - 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. - No major surgery within 2 weeks prior to cycle 1, other than for diagnosis. - A condition that precludes oral route of administration (venetoclax). - No known allergies to both xanthine oxidase inhibitors and rasburicase. - Patient must not require the use of warfarin (because of potential drug-drug interactions that may potentially increase the exposure of warfarin). Blood thinners of other classes are permitted. - Patient may not receive the following agents within 7 days prior to the first dose of venetoclax: - 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. - Patient must not have serious medical or psychiatric illness likely to interfere with participation in this clinical study.