Combining Venetoclax, Rituximab, and Ibrutinib for Treating Chronic Lymphocytic Leukemia

Venetoclax and Delayed Rituximab With Ibrutinib Consolidation Aiming at Undetectable Minimal Residual Disease (uMRD) in Treatment-naïve Patients With Chronic Lymphocytic Leukemia (CLL)

This study is testing if adding ibrutinib to a year-long treatment of venetoclax and rituximab can help people with newly diagnosed Chronic Lymphocytic Leukemia reach a state where the disease is undetectable.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 55 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: IRCCS San Raffaele (Academic / other)
• Drugs / interventions: rituximab, ibrutinib
• Locations: 1 site (Milan, MI)
• Trial ID: NCT04758975 on ClinicalTrials.gov

What this trial studies

This Phase 2, multicenter, open-label interventional study evaluates the effectiveness of adding ibrutinib to a 12-month treatment regimen of venetoclax and rituximab in patients with treatment-naïve Chronic Lymphocytic Leukemia (CLL) who have undetectable minimal residual disease (uMRD). The treatment involves an initial ramp-up of venetoclax followed by a combination with rituximab, with the goal of achieving uMRD status by the end of the treatment cycles. Patients will be monitored for their MRD status to determine the continuation or cessation of therapy based on their response. This approach aims to optimize treatment outcomes for CLL patients.

Who should consider this trial

Good fit: Ideal candidates for this study are treatment-naïve adults aged 18 to 64 years with active CLL requiring treatment.

Not a fit: Patients with a history of prior CLL treatment or those with certain comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve outcomes for patients with CLL by achieving and maintaining undetectable minimal residual disease.

How similar studies have performed: Other studies have shown promising results with similar combinations of targeted therapies in CLL, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Age ≥18 years but \<65 years
2. Active CLL/SLL requiring treatment per iwCLL 2018 criteria
3. No previous therapy for CLL/SLL
4. Adequate bone marrow function:

   1. ANC ≥1.0 x 109/L;
   2. Plt ≥25 x 109/L;
   3. Hgb ≥8.0 g/dl

Exclusion Criteria:

1. Any prior therapy used for treatment of CLL or SLL
2. History of other malignancies, except in situ carcinoma or malignancy treated with curative intent
3. Known or suspected history of Richter's transformation
4. Known hypersensitivity to one or more study drugs
5. Inadequate renal function: CrCl \<30 mL/min
6. Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia
7. Requires the use of warfarin or derivatives
8. Treatment with any of the following within 7 days prior to the first dose of study drug:

   1. Steroid therapy for anti-neoplastic intent
   2. Moderate or strong cytochrome P450 3A (CYP3A) inhibitors (see Appendix G for examples)
   3. Moderate or strong CYP3A inducers (see Appendix G for examples)

Where this trial is running

Milan, MI

• IRCCS Ospedale San Raffaele — Milan, Mi, Italy (Recruiting)

Study contacts

• Study coordinator: Paolo Ghia, MD, PhD

Conditions Chronic Lymphocytic Leukemia