Venetoclax in Combination With BEAM Conditioning Regimen for ASCT in Non-Hodgkin Lymphoma

The purpose of this study is to determine the correct dose and safety of adding a new cancer drug, Venetoclax, to a standard combination of chemotherapy drugs used prior to Autologous stem cell transplant (ASCT) in participants with Non-Hodgkin Lymphoma (NHL). In this study, Venetoclax will be added to BEAM (BCNU or carmustine, etoposide, cytarabine or ara-c, and melphalan). All NHL participants are admitted for conditioning chemotherapy which is given prior to the infusion of stem cells. Venetoclax is a new anti-cancer drug that works by targeting a protein (known as the Bcl-2 protein). By inhibiting or "blocking" this protein, a downstream cascade occurs which results in cancer cells to die. Adding Venetoclax to the standard BEAM conditioning chemotherapy with autologous stem cell transplant is believed to increase the chance of remission. Venetoclax is Food and Drug Administration (FDA) approved for participants with chronic lymphocytic leukemia (CLL). However, Venetoclax is investigational for this study because it is not yet approved for use in participants with NHL or in combination with BEAM chemotherapy.

Inclusion Criteria: * Patients must have histologically confirmed Non-Hodgkin Lymphoma (NHL) including T-cell lymphomas, after at least one prior systemic treatment regimen such as CHOP, R-CHOP, CHOEP, R-EPOCH, R-HyperCVAD, BR, VR-CAP alternating with rituximab and cytarabine, etc. * Patients in complete or partial remission, or in the case of patients with stable or refractory disease are undergoing autologous transplantation because it has been recommended by their treating physician as representing their best treatment option. * ECOG Performance status ≤ 2 at time of consent \[See Appendix I\]. * Patients must have normal organ and marrow function as defined below: * Hemoglobin ≥ 8.0 g/dl * Absolute neutrophil count ≥ 1,000/mcL * Platelet count ≥ 75,000/mcL * Total bilirubin ≤ 1.5X the upper limit of normal (ULN) unless a known history of impaired bilirubin conjugation such as Gilbert's. * AST (SGOT) ≤ 2.5 X institutional ULN * ALT (SGPT) ≤ 2.5 X institutional ULN * Patients must have a calculated serum creatinine clearance \> 50 mL/min using Cockcroft-Gault calculation or based on 24-hour urine collection performed within 7 days prior to treatment. * Cardiac ejection fraction \>45% or clearance by PI or Cardiology * DLCO of \>45% predicted or clearance by PI or Pulmonology * Specific guidelines will be followed regarding inclusion of NHL based on Hepatitis B serological testing as follows: * HBsAg negative, HBcAb negative, HBsAb negative patients are eligible. * HBsAg negative, HBcAb negative, HBsAb positive patients are eligible. * Patients who test positive for HBsAg are ineligible. * Patients with HBsAg negative, but HBcAb positive (regardless of HBsAb status) should have a HBV DNA testing performed and protocol eligibility determined as follows: * If HBV DNA is positive, the patient is ineligible. * If HBV DNA is negative, the patient may be included but must undergo HBV DNA PCR testing monthly x 3 months beginning from the start of treatment * Female patients who are not surgically sterile or postmenopausal (for at least 1year) must practice at least one of the following methods of birth control throughout the duration of study participation and for at least 30 days after study treatment: * Total abstinence from sexual intercourse * A vasectomized partner * Hormonal contraceptives (oral, parenteral, vaginal ring, or transdermal) that started at least 3months prior to study drug administration * Double-barrier method (condom+diaphragm or cervical cup with spermicidal contraceptive sponge, jellies, or cream) * Patients must have the ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: The presence of any of the following will exclude a patient from study enrollment: * Patients who have not recovered from adverse events due to agents administered more than 2 weeks earlier. * Prior treatment toxicities have not resolved to ≤ Grade 2 according to NCI CTCAE Version 5.0 (except clinically unrelated toxicities such as alopecia or peripheral neuropathy). * Patients receiving any other investigational agents. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to Venetoclax or other agents used in this study. * Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Patients who are pregnant or breastfeeding will be excluded from this study because carmustine, etoposide, cytarabine, and melphalan are chemotherapeutic agents with the potential for teratogenic or abortifacient effects. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with carmustine, etoposide, cytarabine, and melphalan, breastfeeding should be discontinued if the mother is treated with these agents. These potential risks may also apply to other agents used in this study. * HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with Venetoclax. In addition, these patients are at increased risk of lethal infections when treated with marrow suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated. HIV testing prior to enrollment is not required for screening but strongly encouraged for patients with no documented prior HIV assessment. * Malabsorption syndrome or other condition that precludes enteral route of Venetoclax administration * Patients with metastatic solid tumor malignancies. Patients who have early stage solid tumors and have completed curative treatment are eligible at the discretion of the primary investigator. Patients with unresected but localized stage prostate cancer or other carcinomas in situ that are undergoing observation are also allowed. Patients with transformed lymphoma and/or underlying indolent lymphoproliferative disorder are allowed at the discretion of the investigator. * Major surgery, other than diagnostic surgery, within 2 weeks. * Medical condition requiring chronic use of high dose systemic corticosteroids (i.e., doses of prednisone higher than 10 mg/day or equivalent). Brief (\