Assessing Minimal Residual Disease by Next- Generation Sequencing to Minimize Exposure in People With CLL or SLL Who Have Been Treated With Venetoclax

Study Overview
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Brief Summary
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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.

Detailed Description
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Screening Phase: Patients will be identified by clinical investigators at participating centers. Patients who sign the screening consent will undergo MRD assessment with the clonoSEQ® assay. If the assessment identifies the patient to be MRD negative, the patient will undergo a repeat MRD assessment ≥ 28 days later. If two consecutive MRD assessments indicate MRD-negativity, the patient will then 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.)

Official Title
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Veneto-STOP Study: Sequential Assessment of Minimal Residual Disease by Next Generation Sequencing to Optimize Outcomes and Minimize Exposure in Venetoclax-Treated CLL/SLL Patients

Conditions
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Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL)

Intervention / Treatment
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* Drug: Venetoclax monotherapy
* Drug: Venetoclax with anti CD20 monoclonal antibody


Participation Criteria
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Eligibility Criteria
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Screening Phase Inclusion Criteria: ≥ 18-years-old Diagnosis of chronic lymphocytic leukemia or small lymphocytic lymphoma confirmed by the enrolling institution Receiving treatment or planning to receive treatment within 30 days 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) Patient has or will have specimen to identify the CLL or SLL clone(s) for future MRD assessments by clonoSEQ® defined as any of the following: 3-5 bone marrow aspirate slides (banked), 3-5 FFPE slides (banked), banked tumor cells or banked DNA collected from the patient at any time from original diagnosis of CLL or SLL to present Peripheral blood, marrow, or lymph node involvement for fresh sample collection 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) If receiving venetoclax in combination with anti-CD20 monoclonal antibody, patients must have completed or discontinued the anti CD20 monoclonal antibody portion of the regimen prior to discontinuing therapy 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 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): Ongoing 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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a multicenter clinical stopping trial for venetoclax-treated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) patients.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Venetoclax monotherapy<br> | Drug: Venetoclax monotherapy<br>* Venetoclax monotherapy<br>|
| Experimental: Venetoclax with anti-CD20 monoclonal antibody<br> | Drug: Venetoclax with anti CD20 monoclonal antibody<br>* Venetoclax with anti CD20 monoclonal antibody<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients able to remain off CLL/SLL directed therapy | This will be described as a percentage of all patients with available data at 12 cycles of follow up (evaluable population). | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Venetoclax, Anti-CD20 monoclonal antibody, 19-395