Phase II Study on the Combination of Ibrutinib and Venetoclax in Treatment naïve Patients With Waldenström Macroglobulinemia
Overview
- Phase
- Phase 2
- Intervention
- IBRUTINIB
- Conditions
- Waldenstrom Macroglobulinemia
- Sponsor
- Dana-Farber Cancer Institute
- Enrollment
- 45
- Locations
- 2
- Primary Endpoint
- Number of Participants With Very Good Partial Response Within 24 Cycles of Therapy
- Status
- Active, not recruiting
- Last Updated
- 9 months ago
Overview
Brief Summary
This study evaluates the safety and efficacy of Ibrutinib combined with Venetoclax (IVEN) in the treatment of adults diagnosed with Waldenstrom's macroglobulinemia (WM) cancer with a specific MYD88 gene mutation.
This research study involves an experimental drug combination of targeted therapies.
The names of the study drugs involved in this study are:
- Venetoclax
- ibrutinib
Detailed Description
* This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied. * The names of the study drugs involved in this study are: * Venetoclax * ibrutinib * The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. * Participants will be on the research study for up to 2 years on combined venetoclax and ibrutinib and 4 years of follow-up . * It is expected that about 50 people will take part in this research study. * The U.S. Food and Drug Administration (FDA) has not approved venetoclax for your specific disease but it has been approved for other uses. -- Venetoclax is a targeted therapy that blocks BCL-2, a protein that is important for the survival of WM cells. Laboratory studies and early clinical data have shown that the investigational new agent, venetoclax, may kill cancer cells and may cause tumors to shrink. * The U.S. Food and Drug Administration (FDA) has approved ibrutinib as a treatment option for this disease. --Ibrutinib is a targeted therapy that blocks BTK. It has been FDA approved in chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), chronic graft vs. host disease (cGVHD), and Waldenstrom's macroglobulinemia (WM). It is also used in research studies in participants with recurrent B-cell lymphoma), diffuse large B-cell lymphoma (DLBCL), and prolymphocytic leukemia. In a study of ibrutinib in relapsed/refractory WM patients, response rates were high and the treatment was well tolerated. * The U.S. Food and Drug Administration (FDA) has not approved the combination of ibrutinib and venetoclax as a treatment for any disease. * The U.S. Food and Drug Administration (FDA) has not approved the MYD88 test. This test is investigational.
Investigators
Jorge J. Castillo, MD
Principal Investigator
Dana-Farber Cancer Institute
Eligibility Criteria
Inclusion Criteria
- •Participants must meet the following criteria on screening examination to be eligible to participate. Screening evaluations including consent, physical exam, and laboratory assessments will be done within 30 days prior to Cycle 1 Day
- •Bone marrow biopsy \& aspirate, and CT C/A/P will be done within 90 days prior to Cycle 1 Day
- •Clinicopathological diagnosis of Waldenström macroglobulinemia \[28\].
- •Known tumor expression of mutated MYD88 performed by a CLIA certified laboratory.
- •Symptomatic disease meeting criteria for treatment using consensus panel criteria from the Second International Workshop on Waldenström macroglobulinemia \[29\].
- •Participants with symptomatic hyperviscosity (e.g. nosebleeds, headaches, blurred vision) must undergo plasmapheresis prior to treatment initiation.
- •Age ≥ 18 years
- •ECOG performance status ≤2 (see Appendix A)
- •Measurable disease, defined as presence of serum immunoglobin M (IgM) with a minimum IgM level of \>2 times the upper limit of normal of each institution is required
- •At the time of screening, participants must have acceptable organ and marrow function as defined below:
Exclusion Criteria
- Not provided
Arms & Interventions
Ibrutinib and Venetoclax
The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. * Ibrutinib will be administered at a predetermined dose, once daily for 28 days * TLS Prophylaxis (Treatment to reduce risk of tumor lysis syndrome) prior to first dose of venetoclax (and for at least the first 2 weeks of treatment) * Venetoclax Cycle 2-24. PO daily, predetermined dosage ramp up during cycle 2.
Intervention: IBRUTINIB
Ibrutinib and Venetoclax
The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. * Ibrutinib will be administered at a predetermined dose, once daily for 28 days * TLS Prophylaxis (Treatment to reduce risk of tumor lysis syndrome) prior to first dose of venetoclax (and for at least the first 2 weeks of treatment) * Venetoclax Cycle 2-24. PO daily, predetermined dosage ramp up during cycle 2.
Intervention: Venetoclax
Outcomes
Primary Outcomes
Number of Participants With Very Good Partial Response Within 24 Cycles of Therapy
Time Frame: The primary objective of VGPR within 24 cycles of therapy was assessed starting at Cycle 3 Day 1 through the End of Treatment visit, range of 2 to 21 months after the initiation of therapy.
Proportion of patients with VGPR to therapy within 24 cycles of therapy initiation. (VGPR is \>90% reduction in serum IgM from baseline)
Secondary Outcomes
- Median Time to Response(24 months)
- Progression Free Survival (PFS) at 48 Months(48 Months)
- Overall Response(72 months)
- Rate of VGPR at 30 Months(30 Months)
- Overall Survival(72 months)
- Number of Participants With Complete Response (CR) After 6 Cycles(6 Cycles (28 day cycle))
- Median Time to Major Response(24 months)
- Progression Free Survival (PFS) at 24 Months(24 months)
- Progression Free Survival (PFS) at 60 Months(60 Months)
- Time to Next Treatment(72 months)
- Number of Participants With Treatment Related Adverse Events as Assessed (CTCAE) Version 5.0(6 Months)
- Number of Participants With Complete Response (CR) After 12 Cycles(12 Cycles (28 day cycle))
- Number of Participants With Complete Response (CR) After 24 Cycles(Complete response to therapy was assessed starting at Cycle 3 Day 1 through the End of Treatment visit, range of 2 to 21 months after the initiation of therapy.)
- Progression Free Survival (PFS) at 36 Months(36 Months)