Assessing treatment cessation in CLL or SLL patients after venetoclax therapy

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

This study tests if people with chronic lymphocytic leukemia or small lymphocytic lymphoma can safely stop taking their venetoclax treatment for a year after showing no signs of the disease.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Memorial Sloan Kettering Cancer Center (Academic / other)
• Locations: 9 sites (Basking Ridge, New Jersey and 8 other locations)
• Trial ID: NCT04419519 on ClinicalTrials.gov

What this trial studies

This study evaluates whether patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have achieved minimal residual disease (MRD) negativity after treatment with venetoclax can safely stop their treatment for at least 12 months. Participants will undergo MRD assessments using the clonoSEQ® assay to confirm their MRD-negative status before entering the intervention phase. The study will compare outcomes between patients receiving venetoclax alone and those receiving it in combination with an anti-CD20 monoclonal antibody.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older diagnosed with CLL or SLL who are currently receiving or planning to receive venetoclax-based therapy.

Not a fit: Patients who are not currently receiving venetoclax or those with active disease that does not meet MRD-negative criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could allow patients to discontinue venetoclax treatment safely, reducing their exposure to medication and potential side effects.

How similar studies have performed: Other studies have shown promising results in similar approaches to treatment cessation in hematological malignancies, suggesting potential for success in this study.

Eligibility criteria

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).

Where this trial is running

Basking Ridge, New Jersey and 8 other locations

• Memorial Sloan Kettering Basking Ridge (All protocol activities) — Basking Ridge, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Monmouth (All protocol activities) — Middletown, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Bergen (All protocol activities) — Montvale, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Commack (All protocol activities) — Commack, New York, United States (Recruiting)
• Memorial Sloan Kettering Westchester (All protocol activities) — Harrison, New York, United States (Recruiting)
• Columbia University — New York, New York, United States (Active_not_recruiting)
• Memorial Sloan Kettering Cancer Center (All Protocol Activities) — New York, New York, United States (Recruiting)
• Memorial Sloan Kettering Nassau (All protocol activities) — Uniondale, New York, United States (Recruiting)
• University of Washington — Seattle, Washington, United States (Active_not_recruiting)

Study contacts

• Principal investigator: Meghan Thompson, MD — Memorial Sloan Kettering Cancer Center
• Study coordinator: Meghan Thompson, MD

Conditions Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Venetoclax; Anti-CD20 monoclonal antibody; 19-395