Acalabrutinib and Venetoclax With or Without Early Obinutuzumab for the Treatment of High Risk, Recurrent, or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Trial Parameters
Brief Summary
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.
Eligibility Criteria
Inclusion Criteria: 1. Patients with a diagnosis of CLL/SLL and indication for treatment by 2018 iwCLL criteria: Cohort 1: Untreated patients with at least 1 high-risk feature (del(17p) or mutated TP53 or del(11q) or unmutated IGHV or complex karyotype) OR ≥65 years of age Cohort 2: Relapsed after and/or refractory to at least one prior therapy 2. Age 18 years or older 3. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2 4. Adequate renal and hepatic function: * 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) * ALT and AST ≤3.0 x ULN, unless clearly due to disease involvement 5. Absolute neutrophil count greater than 750 neutrophils/L, unless thought to be due to marrow infiltration with CLL. Platelet count of greater than 30,000/µl, with no platelet transfusion in 2 weeks prior to regist