Venetoclax in Treating Patients with Relapsed or Refractory Waldenstrom Macroglobulinemia

Inclusion Criteria

• Clinicopathological diagnosis of Waldenstrom’s macroglobulinemia and meeting criteria for treatment using consensus panel criteria from the Second International Workshop on Waldenstrom’s macroglobulinemia
• Measurable disease, defined as presence of serum immunoglobulin M (IgM) with a minimum IgM level of > 2 times the upper limit of normal of each institution is required
• Have received at least one prior therapy for WM
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Absolute neutrophil count >= 1,000/mm^3
• Platelets >= 50,000/mm^3
• Hemoglobin >= 8 g/dL
• Total bilirubin =< 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X the institutional upper limit of normal
• Creatinine clearance >= 50 ml/min
• Not on any active therapy for other malignancies with the exception of topical therapies for basal cell or squamous cell cancers of the skin
• Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or have or will have complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) while participating in the study; and 2) for at least 28 days after discontinuation from the study; men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy; FCBP must be referred to a qualified provider of contraceptive methods if needed
• Able to adhere to the study visit schedule and other protocol requirements
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Any serious medical condition, laboratory abnormality, uncontrolled intercurrent illness, or psychiatric illness/social condition that would prevent the participant from signing the informed consent form
• Concurrent use of any other anti-cancer agents or treatments or any other study agents
• Concurrent administration of medications or foods that are moderate or strong inhibitors or inducers of CYP3A within 7 days prior to first dose of study drug
• Prior exposure to ABT-199 or B-cell chronic lymphocytic leukemia (CLL)/lymphoma 2 (BCL2) inhibitors
• Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, electrocardiography (ECG) finding, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the patient, including symptomatic hyperviscosity; alter the absorption, distribution, metabolism or excretion of ABT-199; or impair the assessment of study results
• Grade > 2 toxicity (other than alopecia) continuing from prior anti-cancer therapy
• Known central nervous system (CNS) lymphoma
• Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening
• New York Heart Association classification III or IV heart failure
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
• Known history of human immunodeficiency virus (HIV), chronic hepatitis B virus (HBV), or hepatitis C (HCV) requiring treatment; Note: Subjects with serologic evidence of prior vaccination to HBV (i.e., hepatitis B virus surface antigen negative [HBs Ag-], anti-HBs+ and anti-hepatitis B virus core negative [HBc-]) and positive anti-HBc from intravenous immunoglobulin (IVIG) may participate
• Lactating or pregnant women
• Inability to swallow tablets
• History of non-compliance to medical regimens
• Unwilling or unable to comply with the protocol