Assessing Minimal Residual Disease to Minimize Exposure in Patients with Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia Who Have Been Treated with Venetoclax, Veneto-STOP Study
- SCREENING PHASE OF THE STUDY
- Diagnosis of chronic lymphocytic leukemia or small lymphocytic lymphoma confirmed by the enrolling institution
- Receiving treatment with a venetoclax-based regimen as defined below: * Venetoclax monotherapy * Venetoclax in combination with anti CD20 monoclonal antibody (Patients must have completed the anti CD20 monoclonal antibody portion of the regimen prior to discontinuing therapy)
- Patients must be receiving commercially supplied venetoclax (+/- anti CD20 monoclonal antibody)
- Have 3-5 bone marrow aspirate slides (fresh or banked), 3-5 formalin-fixed paraffin-embedded (FFPE) slides (fresh or banked), available banked tumor cells or deoxyribonucleic acid (DNA), or fresh blood sample collected from the patient at any time from original diagnosis of CLL/SLL to present to identify the CLL/SLL clone(s) for future MRD assessments by clonoSEQ
- The screening ID sample (high disease burden sample) can be sent prior to start of venetoclax-based therapy to identify the clone for tracking
- INTERVENTION PHASE OF THE STUDY
- Patients must have received venetoclax-based therapy for at least 6 months (including dose interruptions)
- Patients must have two MRD-negative assessments (defined by >= 10^-5 sensitivity) on the peripheral blood by the clonoSEQ assay at least 28 days apart. Given that MRD status is a dynamic endpoint which may improve with time, if a patient is screen failure based on MRD status (i.e. MRD positive at the 10^-5 sensitivity) they may be rescreened for MRD status every three months to assess for study eligibility
- Patients must have achieved a complete or partial remission with the venetoclax-based regimen. Criteria for remission are per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines. For this protocol, bone marrow biopsy/aspirate evaluation is not necessary to determine remission status
- Participation in a clinical trial that supplies venetoclax and/or anti CD20 monoclonal antibody
- Unwilling or unable to participate in all required study evaluations and procedures
- Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local patient privacy regulations)
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.
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.
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 48 months from stopping venetoclax.
Trial Phase Phase II
Trial Type Treatment
Memorial Sloan Kettering Cancer Center
Anthony R. Mato
- Primary ID 19-395
- Secondary IDs NCI-2020-04226
- Clinicaltrials.gov ID NCT04419519