Overview
This study will find out whether people with CLL or SLL who have received treatment with venetoclax, either alone or in combination with another drug, and who are found to be MRD-negative, can stop treatment with venetoclax and remain off-treatment for 12 months or more. The researchers will also see whether study participants remain MRD-negative after they stop treatment with venetoclax.
Description
Screening Phase:
Patients will be identified by clinical investigators at participating centers. Patients who sign the screening consent patients will undergo an MRD assessment with the clonoSEQ assay. If the assessment identifies the patient to be MRD negative, the patient will undergo a repeat MRD assessment no less than 28 days later. If two consecutive MRD assessments indicate MRD-negativity, the patient will then be directed to sign the study intervention phase informed consent form and will undergo the rest of the screening process.
Enrollment
Once the patient fulfills all eligibility criteria, the patient will be enrolled into one of two cohorts based on the type of therapy they are receiving at the time of enrolled:
Cohort A: Venetoclax monotherapy at time of enrollment.
Cohort B: Venetoclax with anti CD20 monoclonal antibody at time of enrollment (The latter includes patients who initiated anti CD20 monoclonal antibody with venetoclax and have since completed the anti CD20 monoclonal antibody portion of the regimen.)
Eligibility
Screening Phase Inclusion Criteria:
- 18-years-old
- 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 (and anti CD20 monoclonal antibody)Have 3-5 bone marrow aspirate slides (fresh or banked), 3-5 FFPE slides (fresh or banked), available banked tumor cells or DNA, or fresh blood sample collected from the patient at any time from original diagnosis of CLL to present to identify the CLL 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.
Study Intervention Phase Inclusion Criteria:
- 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 iwCLL 2018 guidelines. For this protocol, bone marrow biopsy/aspirate evaluation is not necessary to determine remission status.
Exclusion Criteria (both study phases):
- 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).