This phase II trial studies how well acalabrutinib and venetoclax with or without early obinutuzumab work for the treatment of chronic lymphocytic leukemia or small lymphocytic lymphoma that is high risk, has come back (recurrent), or does not respond to treatment (refractory). Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Venetoclax may stop the growth cancer cells by blocking BCL-2 protein needed for cell growth. Immunotherapy with monoclonal antibodies, such as obinutuzumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving acalabrutinib and venetoclax together with early obinutuzumab may improve clinical outcomes and control the disease.
Age 18 years or older
Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2
Total bilirubin ≤1.5 x upper limit of normal (ULN) or ≤3 x ULN for patients with Gilbert's disease
Creatinine clearance >50 mL/min (calculated according to institutional standards or using Cockcroft-Gault, MDRD, or CKD-EPI formula)
Prior treatment with combined BTKi and BCL2i where patients do not achieve at least partial response or progress and need new treatment within 2 years of completing fixed-duration combined treatment.
Major surgery, radiotherapy, chemotherapy, biologic therapy, immunotherapy, investigational therapy or live virus vaccination within 3 weeks prior to the first dose of the study drugs, unless patients have rapidly progressive disease, in which case, washout will be 3 drug half-lives
History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
Uncontrolled clinically significant active infection (viral, bacterial, and fungal)
Parallel
Acalabrutinib
DrugGiven PO
Obinutuzumab
Biological/VaccineGiven IV
Venetoclax
DrugGiven PO
Disease assessment of bone marrow (BM) undetectable-minimal residual disease,10-4 sensitivity (MRD4) (Treatment-naive [TN] cohort)
Disease assessment of BM undetectable-MRD4 (Relapsed/refractory [R/R] cohort)
Incidence of adverse events
Toxicities (defined as prolonged grade \>= 3 neutropenia or thrombocytopenia lasting \> 42 days; febrile neutropenia; hospitalization due to infection; early death; major bleeding due to thrombocytopenia) will be monitored for each treatment arm separately using the Bayesian method of Thall, Simon and Estey.
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M.D. Anderson Cancer Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator
AstraZeneca
Collaborator
Genentech, Inc.
Collaborator
