Clinical Research Directory

Inclusion Criteria: * Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) diagnosis * Patients must have been diagnosed with CLL (\> 5000 B-cells per microliter of peripheral blood at any point during the course of their disease) or small lymphocytic lymphoma (SLL) with \<5000 B-cells per microliter of blood but with disease-associated lymphadenopathy by 2018 IWCLL criteria * Prior treatment * Patients must be currently receiving CLL/SLL directed therapy with a BTKi (i.e., ibrutinib, acalabrutinib, zanubrutinib) for at least six months * The dose of Bruton Tyrosine Kinase Inhibitor (BTKi) must be stable for at least the past three months * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Detectable or measurable CLL/SLL in blood or imaging during the screening period. Detectable CLL/SLL in the blood is defined either by elevation in absolute lymphocyte count or by diagnostic flow cytometry from blood demonstrating presence of CLL cells * Low Tumor Lysis Syndrome (TLS) risk, defined as having all lymph nodes less than 5 centimeters (cm) in diameter (radiographically) and absolute lymphocyte count less than 25 x 109/liter (L) in blood, within 30 days of enrollment * Required initial laboratory values * Absolute Neutrophil Count (ANC) 1,000/ cubic millimeters (mm3) except if due to bone marrow involvement * Platelet Count (untransfused) 30,000/cubic millimeters (mm3) except if due to bone marrow involvement * Calc. Creatinine Clearance 40 milliliters per minute (mL/min) (by Cockcroft-Gault) * Bilirubin 1.5 x upper limit of normal (ULN) except if due to liver involvement, hemolysis, or Gilbert's disease * Aspartate Aminotransferase (AST) / Alanine Aminotransferase (ALT) 2.5 x upper limit of normal (ULN) except if due to liver involvement * Other * Patients must be able to swallow oral medications and not have the following conditions: disease significantly affecting gastrointestinal absorption, resection of the stomach or small bowel, partial or complete bowel obstruction * Patients must be able to receive either a xanthine oxidase inhibitor or rasburicase Exclusion Criteria: * Prior treatment * Patients must not have progression of CLL/SLL on Bruton Tyrosine Kinase Inhibitor (BTKi) therapy prior to initiation of the study therapy * Patients must not have received the combination of Bruton Tyrosine Kinase Inhibitor (BTKi)+ venetoclax previously * Comorbid conditions or other active diseases * Patients must not have any history of Richter's transformation or prolymphocytic leukemia * If evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable and be on suppressive therapy, if indicated * Please note: Intravenous immunoglobulin (IVIG) can cause a false positive hepatitis B serology. If patients receiving routine IVIG have core antibody or surface antigen positivity without evidence of active viremia (negative hepatitis B DNA) they may still participate in the study, must have hepatitis serologies and hepatitis B DNA monitored periodically by the treating physician * If history of hepatitis C virus (HCV) infection, must be treated with undetectable HCV viral load * Patients with Class III or Class IV heart failure by New York Heart Association, those with unstable angina, and those with uncontrolled arrhythmia are not eligible * Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral therapy are eligible for this trial * Concomitant medications * Patients must not be receiving active systemic anticoagulation with heparin or warfarin. Patients on warfarin must discontinue the drug for at least 10 days prior to registration on the study. * Chronic concomitant treatment with strong inhibitors of CYP3A4/5 is not recommended on this study. Patients on strong CYP3A inhibitors must discontinue the drug for 14 days prior to registration on the study or discuss with the study principal investigator * Chronic concomitant treatment with strong CYP3A4/5 inducers is not recommended. Patients must discontinue the drug 14 days prior to registration on the study or discuss with the study principal investigator * Patients must not require more than 20 milligrams (mg) prednisone or equivalent corticosteroid daily * Patients must not have uncontrolled active systemic infection requiring intravenous antibiotics