Phase II Study of Acalabrutinib and Venetoclax With or Without Early Obinutuzumab for Treating High-Risk or Recurrent Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

What this Trial Is About

Researchers are evaluating how well a combination of acalabrutinib and venetoclax, with or without early obinutuzumab, works to treat high-risk, recurrent, or refractory chronic lymphocytic leukemia CLL or small lymphocytic lymphoma SLL. This phase II trial aims to improve the rate of undetectable minimal residual disease in the bone marrow, which is an indicator of treatment success. The study also investigates safety, response rates, progression-free survival, and pharmacokinetics of the drugs. Participants are randomly assigned to one of two groups. In Arm I, patients receive acalabrutinib orally twice daily and start venetoclax weekly from cycle 3, then daily from cycle 4. Those with residual disease at cycle 15 receive obinutuzumab intravenously during cycles 15 to 20. In Arm II, patients start acalabrutinib in cycle 2, venetoclax similarly, and receive obinutuzumab early during cycles 1 to 6, with additional doses if residual disease remains later. Treatment cycles last 28 days or 42 days for cycle 14 and continue up to 26 cycles unless disease progresses or side effects prevent continuation. During the study, participants undergo regular assessments including bone marrow and blood tests to measure minimal residual disease and monitor response using established criteria. Researchers also track adverse events and collect pharmacokinetic data to understand drug levels. After completing treatment, patients are followed periodically to observe long-term outcomes and relapse. The total participation duration can be up to about two years, depending on treatment cycles and follow-up.

Acalabrutinib and Venetoclax With or Without Early Obinutuzumab for the Treatment of High Risk, Recurrent, or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma