This phase II trial assesses minimal residual disease to minimize exposure in patients with chronic lymphocytic leukemia or small lymphocytic leukemia who have been treated with venetoclax. Stopping treatment with venetoclax in MRD-negative chronic lymphocytic leukemia or small lymphocytic leukemia patients could help prevent the serious side effects that can occur during long-term treatment with this drug. This trial may help researchers find out whether patients who are currently receiving treatment with venetoclax can stop treatment and remain off-treatment for at least 12 months, if they are free of residual disease (MRD-negative) when they stop treatment.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT04419519.
PRIMARY OBJECTIVE:
I. To evaluate whether patients are able to remain off chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) directed therapy at 12 cycles (1 cycle = 28 days) following venetoclax-based treatment discontinuation.
SECONDARY OBJECTIVES:
I. To estimate the cumulative incidence of minimal residual disease (MRD) positivity during the study observation period of 36 cycles following discontinuation.
II. To estimate the cumulative incidence of new CLL/SLL directed therapy initiation at 36 cycles following venetoclax-based treatment discontinuation.
III. To estimate progression-free survival (PFS) as measured from start of treatment free observation.
IV. To estimate overall survival (OS) as measured from start of treatment free observation.
V. To evaluate whether outcomes (proportion of patients able to remain off CLL/SLL directed therapy, PFS, OS) at 12 cycles following treatment discontinuation is different among patients previously treated with venetoclax monotherapy versus (vs.) venetoclax in combination with anti-CD20 antibody.
VI. To estimate the overall response rate (ORR) and the complete response rate (CRR) in the subset of patients who require retreatment with CLL/SLL directed therapy during study observation period, described in aggregate and separated by CLL/SLL-directed treatment regimen received in retreatment.
VII. To estimate the minimal residual disease negativity rate in the subset of patients who require retreatment with CLL/SLL directed therapy during study observation period.
VIII. To describe the adverse event profile for venetoclax-based therapy retreatment.
IX. Quality of life assessment (AQoL-8D) pre- and post-venetoclax discontinuation for MRD negative patients.
X. To describe the baseline mutational and cytogenetic profiles of patients (including cytogenetics, next generational sequencing mutational profiles and IGHV mutational status) prior to the venetoclax treatment under study and at progression, if this testing is available for patients.
OUTLINE:
Patients stop receiving treatment with venetoclax and undergo collection of blood samples every 3 months for 36 months to find out whether blood and bone marrow has any remaining active cancer cells (MRD status). Patients whose cancer comes back and need to re-start treatment with venetoclax before 36 months continue to undergo MRD testing for at least another year, but no longer than 24 months from stopping venetoclax. Patients also undergo magnetic resonance imaging (MRI) or computed tomography (CT) scans as clinically indicated.
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorMeghan Caitlin Thompson
