Venetoclax, Carmustine, Etoposide, Cytarabine, and Melphalan before Stem Cell Transplant in Treating Patients with Relapsed or Refractory Non-Hodgkin Lymphoma

Inclusion Criteria

• Subjects must have histologically confirmed diagnosis of non-Hodgkin’s lymphoma that is refractory after upfront induction therapy, in partial remission or worse after salvage, or relapsed. Excluded histologies are post-transplant lymphoproliferative disorder, and chronic lymphocytic leukemia/small lymphocytic lymphoma. All other histologies are eligible. These include but are not limited to: diffuse-large B-cell lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma (PTCL), hairy cell leukemia (classic or variant), lymphoblastic lymphoma, prolymphocytic leukemia (T or B-cell), follicular lymphoma (grades I, II, and III), marginal zone lymphoma, transformed indolent lymphoma, grey zone lymphoma, and undifferentiated B-cell lymphoma. Patients with non-Hodgkin's lymphoma (NHL) who are at high risk of relapse can be regardless of response * High risk is defined as 1) requiring 3 or more lines of therapy, 2) transformed lymphoma, 3) relapse within 12 months of day (D)1 of last cycle of induction chemotherapy, 4) mantle cell lymphoma (MCL) or PTCL undergoing consolidation with ASCT in CR1/PR1
• Expected survival of more than six months
• Age > 18 years
• Karnofsky performance status >= 80%
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 3 x upper limits of normal (ULN) unless due to disease (within 1 week prior to initiation of treatment)
• Total bilirubin < 2 x ULN unless due to disease (within 1 week prior to initiation of treatment)
• Calculated glomerular filtration rate (GFR) 30 ml/min or greater (within 1 week prior to initiation of treatment)
• Absolute neutrophil count (ANC) > 500 cells/mm^3 (within 1 week prior to initiation of treatment)
• Platelet count > 50 mm^3 (within 1 week prior to initiation of treatment)
• Left ventricular ejection fraction >= 40% (within 6 weeks of start of treatment)
• Diffusion capacity of carbon monoxide (DLCO) >= 50% predicted (within 6 weeks of start of treatment)
• Ability to collect 2 x 10^6/kg CD34+ cells for transplantation
• Patient must be otherwise eligible for autologous stem cell transplantation (ASCT) per local institutional guidelines
• No serious disease, or condition, that, in the opinion of the investigator, would compromise the patient’s ability to participate in the study
• Subjects must have the ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Subjects who sustained a complete metabolic response (CMR) by positron emission tomography (PET)-computed tomography (CT) (5-point scale of < 3) unless lymphoma relapsed within 12 months from the first day of last cycle of induction chemotherapy or patients have "high risk disease"
• Subjects receiving any other investigational agents
• Patients with central nervous system (CNS) involved by lymphoma can be included if CNS disease is deemed controlled prior to enrollment as determined by the investigator. Patients with uncontrolled CNS disease will be excluded
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to venetoclax or other agents used in this study
• Subjects 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 human immunodeficiency virus (HIV) positive and receiving combination antiretroviral therapy will be excluded; because of the potential for pharmacokinetic interactions with venetoclax
• Patients receiving strong inhibitors or inducers of CYP3A4. All such medications would have to be discontinued for 72 hours prior to start of venetoclax
• Female patients who are pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women. Male or female patients, who are sexually active and of the child bearing age, must be willing to practice accepted birth control measures