Phase 2 Study of Acalabrutinib Plus Venetoclax for Relapsed Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma After First-Line Fixed-Duration BTKi and BCL2i Treatment

What this Trial Is About

Researchers are evaluating the effectiveness and safety of a limited-duration combination therapy using acalabrutinib and venetoclax in patients with relapsed chronic lymphocytic leukemia CLL or small lymphocytic lymphoma SLL. The study focuses on patients who previously responded to a first-line combination treatment of covalent BTKi plus BCL2i, with or without obinutuzumab, and maintained a response for at least two years after that treatment. This phase 2 study aims to assess overall response rates and outcomes for this second-line treatment approach. Participants are grouped into low or high disease risk cohorts based on genetic markers such as IGHV mutation and TP53 aberrancy. The treatment begins with 2 cycles of acalabrutinib alone, followed by combination therapy with acalabrutinib and venetoclax for either 12 or 22 cycles depending on the risk group. After treatment, participants enter a follow-up period lasting up to 3 or 4 years, making the total study duration around 5 years for each participant. During the study, participants will undergo regular evaluations including response assessments at various treatment cycles, monitoring of progression-free and overall survival, and measurement of minimal residual disease after treatment. Safety and tolerability of the combination therapy will be closely tracked throughout the 5-year period. Participants will have scheduled visits for treatment administration, laboratory tests, and clinical assessments to monitor their health and study outcomes.

Phase 2 Study of Disease Risk Mutation-Guided Finite Acalabrutinib+Venetoclax for Relapsed CLL Post-1L Finite cBTKi+BCL2i ± Obinutuzumab