Zanubrutinib and Venetoclax as Initial Therapy for CLL With Obinutuzumab Consolidation in Patients With Minimal Residual Disease Positivity (BruVenG)

Description

Bruton's tyrosine kinase inhibitors (BTKi), anti-CD20 antibodies, and the B cell lymphoma 2 inhibitor (BCL-2i) venetoclax are drug classes used to treat patients with chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL). Anti-CD20 therapy may not be required for all patients. The investigators hypothesis is that it may be better to give anti-CD20 therapy (obinutuzumab) only to patients that still have detectable cancer in their blood (minimal residual disease \[MRD\]) after being treated with a combination of two oral medications, zanubrutinib (a BTKi ) and venetoclax (a BCL-2i), instead of giving a combination of three drugs to all patients from the start of treatment. This strategy, if effective, will prevent overtreatment with anti-CD20 antibodies; reduce side effects of treatment while potentially increasing MRD negativity rates; and will possibly make the anti-CD20 antibody therapy more effective given the low tumor burden present when utilized. This study will test t

Trial Eligibility

Inclusion Criteria: * Participant must have confirmed diagnosis of CLL/SLL * Participant must have indications for treatment * Participants of childbearing potential must be willing to comply with pregnancy prevention interventions Exclusion Criteria: * Previous exposure to any systemic anti-cancer therapy as a treatment for CLL/SLL, including but not limited to chemotherapy, immunotherapy, radiotherapy, hormone therapy (other than contraceptives, hormone-replacement therapy or megestrol acetate) or investigational therapy. * History of malignancy except for non-melanoma skin cancers. Participants treated with curative intent via methods of local resection and or locally targeted anticancer treatment and are free of malignancy for at least 5 years from treatment end will be allowed to enroll. * Requires chronic immunosuppressive therapy for any reason or was treated with immunosuppressive therapy within 6 months of study entry. * Participants with active autoimmune hemolytic anemia or immune thrombocytopenia purpura. * Prolymphocytic leukemia or Richter's Transformation. * Active bleeding, or history of bleeding diathesis (e.g., hemophilia or von Willebrand disease). * Participant requires warfarin or equivalent vitamin K antagonist. * Uncontrolled or active significant infection requiring systemic treatment * History of suspected or confirmed PML * Myocardial infarction within 6 months before screening. * Unstable angina within 3 months before screening. * New York Heart Association class III or IV congestive heart failure * History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes). * Patients with stroke or CNS hemorrhage within 6 months. * Pregnant or breastfeeding. * Major surgical procedure within 28 days of first dose of study drug. * Has difficulty with or is unable to swallow oral medication or has significant gastrointestinal disease that would limit absorption of oral medication. * Participant is positive for human immunodeficiency virus (HIV). * Known hypersensitivity reactions (e.g., anaphylaxis) to obinutuzumab or any of the excipients, including serum sickness with prior obinutuzumab use. * Vaccination with live vaccine ≤28 days prior to start of treatment.

Study Info

Interventions

Locations Recruiting

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