Bendamustine, Obinutuzumab, and Venetoclax in Patients With Untreated Mantle Cell Lymphoma

Inclusion Criteria: * Signed informed consent form * Ability and willingness to comply with the requirements of the study protocol * Histologic diagnosis of mantle cell lymphoma. This diagnosis must be confirmed at the treating center and patients must have this diagnosis confirmed by at least one of the following criteria: * Fluorescent in situ hybridization (FISH) or conventional cytogenetics positive for t(11;14) * Cyclin D1 positive by immunohistochemistry * Documentation by a hematopathologist at the treating institution that there is pathologic evidence of mantle cell lymphoma if neither criteria above are met * No previous therapy for diagnosis of lymphoma (note that in patients deemed to be high-risk for tumor lysis syndrome or for rapid clinical deterioration due to symptomatic disease by the investigator, a short course of steroids designed to decrease tumor burden is permitted) * Eastern Cooperative Oncology Group performance status of 0, 1, or 2 * Hemoglobin ≥ 9 g/dL * Absolute neutrophil count ≥ 1.5 x 10⁹/L * Platelet count ≥ 75 x 10⁹/L * Serum creatinine ≤ 2.0 mg/dL or creatinine clearance ≥ 40 mL/min * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN) * Total bilirubin \< 1.5 x ULN (or ≤ 3 x ULN for patients with documented Gilbert syndrome) * NOTE: Patients with renal or hepatic impairment that is disease-related (ie, hydronephrosis, hepatic involvement) in the opinion of the investigator but who meet all other eligibility criteria may be considered for enrollment in consultation with the investigational new drug (IND) sponsor, Dr. Jonathon Cohen. Documentation of prior adequate renal/hepatic function and clear association with the disease will be required * For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of \< 1% per year during the treatment period and for at least 30 days after the last dose of venetoclax or 18 months after the last dose of obinutuzumab, whichever is longer * A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus) * Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices * The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception * For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below: * With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of \< 1% per year during the treatment period and for at least 6 months after the last dose of obinutuzumab. Men must refrain from donating sperm during this same period * With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 6 months after the last dose of obinutuzumab to avoid exposing the embryo * The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception Exclusion Criteria: * 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. * Individuals in documented remission without treatment for ≥ 2 years prior to enrollment may be included at the discretion of the investigator. Patients with more recently treated low risk prostate cancer, thyroid cancer, or ductal carcinoma in situ (DCIS) who are felt to be at low risk for progression and who are not currently taking any chemotherapy, hormonal therapy or other anti-cancer therapy are eligible. Patients who have been treated and been in remission for \< 2 years must be cleared with the study chair prior to initiating study therapy * 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 * Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment * Requires the use of warfarin (because of potential drug-drug interactions that may potentially increase the exposure of warfarin) * Received strong or moderate cytochrome P450 3A (CYP3A) inhibitors or inducers within 7 days of initiating venetoclax. Consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit within 3 days prior to 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 and to remain on hepatitis B prophylaxis during therapy * Patients with human immunodeficiency virus (HIV) are eligible if they have a cluster of differentiation 4 (CD4) count \> 400 and an undetectable viral load. They must be under the care of an infectious disease physician and have no history of an acquired immune deficiency syndrome (AIDS)-defining illness (except lymphoma) * Receipt of live-virus vaccines within 28 days prior to the initiation of study treatment or need for live-virus vaccines at any time during study treatment * Pregnant or lactating, or intending to become pregnant during the study * Women of childbearing potential must have a negative serum pregnancy test result within 21 days prior to initiation of study drug * Recent major surgery (within 6 weeks prior to the start of cycle 1, day 1) other than for diagnosis or line placement * Malabsorption syndrome or other condition that precludes enteral route of administration * Known allergy to both xanthine oxidase inhibitors (ie, allopurinol) and rasburicase