STop and Restart Acalabrutinib In fRail Patients With Previously Untreated Chronic Lymphocytic Leukemia

The irreversible Bruton's Tyrosine Kinase (BTK) inhibitor acalabrutinib (ACA) has potent clinical activity as a single agent in patients with treatment naive and Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL). However, a growing body of concerns is raising regarding the unlimited administration of targeted therapy as BTKi. First, long-term treatments expose the patients to increased risk of specific adverse events (infections, bleeding events or cardiovascular problems). Second, continuous administration might also increase the risk of clonal evolution and therapeutic resistance resulting from genetic alterations such as BTK or PLCG2 mutations. Discontinuation of therapy after a fixed period is expected to prevent these events. Rapid and deep responses yielded by ACA in elderly patients pave the way of investigating a limited 18-months period schedule. This study aims to investigate the 1-year PFS upon ACA discontinuation and efficacy of restarting ACA upon symptomatic relapse.

NCT Number	NCT04963946
Lead Sponsor	French Innovative Leukemia Organisation
Conditions	Untreated Chronic Lymphocytic Leukemia
Enrollment	160 participants
Start Date	2021-10-18
Primary Completion	2025-08-01 (estimated)
Study Completion	2028-08-01 (estimated)
Updated on ClinicalTrials.gov	2025-12-03