SOHO 2020: Chemotherapy-Free Combination Therapy for CLL Under Study in Phase III Trial
Posted: Monday, September 21, 2020
Jennifer R. Brown, MD, PhD, of Dana-Farber Cancer Institute, Boston, and international colleagues are conducting a phase III trial comparing acalabrutinib plus venetoclax with or without obinutuzumab with the investigator’s choice of chemoimmunotherapy for patients with previously untreated chronic lymphocytic leukemia (CLL) without del(17p) or TP53 mutation. The investigators believe the combination of a Bruton’s tyrosine kinase (BTK) inhibitor with an anti-CD20 antibody and a BCL-2 inhibitor in a chemotherapy-free fixed-duration regimen may potentially improve outcomes over the front-line standard of care in this patient population. They discussed the framework and the study endpoints in a presentation during the virtual edition of the 2020 Society of Hematology Oncology (SOHO) Annual Meeting (Abstract CLL-092).
“I am excited about the potential of a time-limited combination of a second-generation BTK inhibitor with venetoclax, hopefully leading to high rates of undetectable minimal residual disease and long remissions off therapy, particularly for young fit patients,” Dr. Brown told JNCCN 360.
The design of this newer randomized, global, multicenter study (ACE-CL-311) will include three treatment arms: arm A = acalabrutinib plus venetoclax; arm B = acalabrutinib, venetoclax, and obinutuzumab; and arm C = chemoimmunotherapy. The expected enrollment of this currently recruiting study is about 780 patients, divided evenly among the three arms. Patients who have received any prior CLL-specific therapies or who have del(17p) or TP53 mutation are excluded from the study.
The primary study endpoint is an independent review committee–assessed progression-free survival (arm A vs. arm C). Among the many secondary studies, endpoints are investigator-assessed progression-free survival (arm A vs. arm C), independent review committee–assessed and investigator-assessed progression-free survival (arm B vs. arm C), the rate of undetectable minimal residual disease, objective response rate, duration of response, event-free survival, time to next therapy, and overall survival. In addition, the incidence and severity of adverse events as well as patient-reported outcomes will be assessed.