A Randomized Phase II Study of Acalabrutinib (ACA) + Venetoclax (VEN) +/- Early Obinutuzumab (OBIN) for Patients With Chronic Lymphocytic Leukemia (CLL)
M.D. Anderson Cancer Center
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.
Description
PRIMARY OBJECTIVES: I. Demonstrate improvement in bone marrow (BM) undetectable-minimal residual disease,10-4 sensitivity (MRD4) from 40% to 70% after 7 courses of combined acalabrutinib (ACA) and venetoclax (VEN) (end of C9 overall) with addition of early obinutuzumab (OBIN). (Treatment-naive \[TN\] cohort) II. Demonstrate improvement in BM undetectable-MRD4 from 40% to 70% after 12 courses of combined acalabrutinib (ACA) and venetoclax (VEN) (end of cycle \[C\]14 overall) with addition of early obinutuzumab (OBIN). (Relapsed/refractory \[R/R\] cohort) SECONDARY AND EXPLORATORY OBJECTIVES:…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
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 * Creati…
Interventions
- DrugAcalabrutinib
Given PO
- BiologicalObinutuzumab
Given IV
- DrugVenetoclax
Given PO
Location
- M D Anderson Cancer CenterHouston, Texas