Phase II Study of IRD (Ixazomib, Lenalidomide, Dexamethasone) Post Autologous Stem Cell Transplantation Followed by Maintenance Ixazomib or Lenalidomide for Multiple Myeloma
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT02253316
- Lead Sponsor
- Washington University School of Medicine
- Brief Summary
The purpose of this research study is to evaluate a treatment regimen called IRD which will be given to participants after their stem cell transplant in an effort to help prolong the amount of time the participants are disease-free after transplant. IRD is a three-drug regimen consisting of ixazomib, lenalidomide (also called Revlimid), and dexamethasone. After 4 cycles of IRD, the participants will be randomized to receive maintenance therapy either with ixazomib or lenalidomide.
- Detailed Description
Based on the further need to improve progression-free survival and overall survival post-autologous stem cell transplantation (ASCT) for multiple myeloma and the benefits seen of consolidation/maintenance treatment with immunomodulatory drugs thalidomide and lenalidomide and the proteasome inhibitor bortezomib, the natural next step is to evaluate combination regimens of immunomodulatory drugs and proteasome inhibitors as consolidation/maintenance post-ASCT. The regimen consisting of ixazomib, lenalidomide, and dexamethasone (IRD) has been shown to have low toxicity, and the availability of an oral formulation of ixazomib allows for easier administration when compared to bortezomib.
In this study, following consolidation with IRD, patients will be randomized to maintenance therapy with lenalidomide or ixazomib in order to collect pilot data comparing the toxicity and efficacy of maintenance therapy with immunomodulatory drugs and proteasome inhibitors.
09/23/2019: Upon review of the interim analysis, there will be no further randomizations into the maintenance portion of the trial. All patients will be enrolled into the lenalidomide arm with the exception of those who discontinue lenalidomide during the consolidation phase due to toxicity. Patients who discontinue lenalidomide may be enrolled into the ixazomib arm following approval from the principal investigator.
09/30/2021: Following analysis 4 in 2021, analysis of the primary endpoint, all patients receiving lenalidomide maintenance will be transitioned off-study. Patients receiving ixazomib may remain on trial until disease progression or unacceptable toxicity at the discretion of the treating physician and the site principal investigator.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 236
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Consolidation: Ixazomib, Lenalidomide, & Dexamethasone Ixazomib Consolidation therapy will begin between Day 80 and Day 120 following ASCT and will consist of four 28-day cycles of IRD (ixazomib, lenalidomide, \& dexamethasone). Barring dose modifications for toxicity, 4 mg of ixazomib and 40 mg of dexamethasone will be administered on Days 1, 8, and 15, and 15 mg of lenalidomide will be administered on daily on Days 1-21. Maintenance Arm 1: Ixazomib Ixazomib Ixazomib will be administered on Days 1, 8, and 15 of a 28-day cycle at a starting dose of 4 mg until patient progresses or experiences an unacceptable toxicity. Consolidation: Ixazomib, Lenalidomide, & Dexamethasone Lenalidomide Consolidation therapy will begin between Day 80 and Day 120 following ASCT and will consist of four 28-day cycles of IRD (ixazomib, lenalidomide, \& dexamethasone). Barring dose modifications for toxicity, 4 mg of ixazomib and 40 mg of dexamethasone will be administered on Days 1, 8, and 15, and 15 mg of lenalidomide will be administered on daily on Days 1-21. Consolidation: Ixazomib, Lenalidomide, & Dexamethasone Dexamethasone Consolidation therapy will begin between Day 80 and Day 120 following ASCT and will consist of four 28-day cycles of IRD (ixazomib, lenalidomide, \& dexamethasone). Barring dose modifications for toxicity, 4 mg of ixazomib and 40 mg of dexamethasone will be administered on Days 1, 8, and 15, and 15 mg of lenalidomide will be administered on daily on Days 1-21. Maintenance Arm 2: Lenalidomide Lenalidomide Lenalidomide will be administered daily continuously for a 28-day cycle at a starting dose of 10 mg. If lenalidomide is tolerated well (i.e. no dose modification required) during the first three cycles, lenalidomide dose will be increased to 15 mg daily and will continue until patient progresses or experiences an unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Number of Participants With Improvement in Minimal Residual Disease (MRD) After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment) For the purposes of this study, a patient will be considered as having minimal residual disease if a positive result (1x10E06) is obtained using the Adaptive Clonoseq MRD testing.
- Secondary Outcome Measures
Name Time Method Compare Toxicity Between the Two Maintenance Arms 30 days after the completion of maintenance treatment (estimated to be Day 1125 of maintenance treatment) The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.
Compare Response Rate Between the Two Maintenance Arms Through completion of maintenance treatment (estimated to be day 1095 of maintenance treatment) * Response will be determined by the International Myeloma Working Group (IMWG) Uniform Response Criteria. Response includes stringent complete response (sCR) and complete response (CR).
* sCR requires all of the following:
* CR as defined below
* Normal free light chain ratio (0.26-1.65)
* Absence of clonal cells in the bone marrow by immunohistochemistry or immunofluorescence
* CR requires all of the following:
* Disappearance of monoclonal protein by both protein electrophoresis and immunofixation studies from the blood and urine
* If serum and urine monoclonal protein are unmeasurable, Normal free light chain ratio (0.26-1.65)
* \<5% plasma cells in the bone marrow
* Disappearance of soft tissue plasmacytomaAssociation of Overall Survival With MRD-positivity Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study) Overall survival (OS) will be defined as time from ASCT to death due to any causes, and survivors will be censored at withdrawal or study closeout.
Response Rate of IRD Consolidation After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment) For the purposes of this study, response rate is defined as the improvement in complete response rate. Response will be determined by the International Myeloma Working Group (IMWG) Uniform Response Criteria.
Overall Survival of IRD Consolidation Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study) Overall survival (OS) will be defined as time from ASCT to death due to any causes, and survivors will be censored at withdrawal or study closeout.
Toxicity of IRD Consolidation After 4 cycles of IRD consolidation treatment (approximately Day 112 of consolidation treatment) For the purposes of this study, toxicity will be defined as inability to receive 4 cycles of IRD consolidation due to toxicity.
MRD-negative Rate After ASCT Prior to beginning consolidation treatment (Day -28 to Day 0) For the purposes of this study, a patient will be considered as having minimal residual disease if a positive result (1x10E06) is obtained using the Adaptive Clonoseq MRD testing
Association of Progression-free Survival With MRD-negativity Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study) Progression-free survival (PFS) will be defined as time from ASCT to progression, relapse, or death, whichever occurs first, and those event-free survivors will be censored at withdrawal or study closeout.
Association of Progression-free Survival With MRD-positivity Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study) Progression-free survival (PFS) will be defined as time from ASCT to progression, relapse, or death, whichever occurs first, and those event-free survivors will be censored at withdrawal or study closeout.
Progression-free Survival of IRD Consolidation Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study) Progression-free survival (PFS) will be defined as time from ASCT to progression, relapse, or death, whichever occurs first, and those event-free survivors will be censored at withdrawal or study closeout.
Compare Progression-free Survival Between the Two Maintenance Arms Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study) Progression-free survival (PFS) will be defined as time from ASCT to progression, relapse, or death, whichever occurs first, and those event-free survivors will be censored at withdrawal or study closeout.
Compare Overall Survival Between the Two Maintenance Arms Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study) Overall survival (OS) will be defined as time from ASCT to death due to any causes, and survivors will be censored at withdrawal or study closeout.
Rate of MRD-positive to MRD-negative Conversion Between the Two Maintenance Arms Cycle 13 Day 1 of maintenance treatment (Approximately Day 364 of maintenance treatment) Association of Overall Survival With MRD-negativity Up to 18 months after completion of maintenance therapy (Up to 5 years after starting the study) Overall survival (OS) will be defined as time from ASCT to death due to any causes, and survivors will be censored at withdrawal or study closeout.
Trial Locations
- Locations (10)
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
University of California, San Francisco
🇺🇸San Francisco, California, United States
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Tennessee Oncology, PLLC
🇺🇸Nashville, Tennessee, United States
Colorado Blood Cancer Institute
🇺🇸Denver, Colorado, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
City of Hope
🇺🇸Duarte, California, United States
Emory University - Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States