Study of Bendamustine and IXAZOMIB (MLN9708) Plus Dexamethasone in Relapsed/Refractory Multiple Myeloma
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT02477215
- Lead Sponsor
- Parameswaran Hari
- Brief Summary
This Phase I/II study is designed to first identify doses of MLN9708 and bendamustine that are associated with an acceptable adverse event profile when delivered together in 28-day cycles. Additionally, the study aims to assess the efficacy of the combination in patients with relapsed/refractory multiple myeloma. Responders (stable disease or more), will continue to receive up to eight cycles total in the absence of further progressive disease.
- Detailed Description
OVERVIEW: This Phase I/II study is designed to first identify doses of MLN9708 and bendamustine that are associated with an acceptable adverse event profile when delivered together in 28-day cycles. Additionally, the study aims to assess the efficacy of the combination in patients with relapsed/refractory multiple myeloma. Responders (stable disease or more),will continue to receive up to eight cycles total in the absence of further progressive disease.
OVERVIEW OF THE DOSE ESCALATION/DE-ESCALATION: This study aims to assess the combination's efficacy in patients with relapsed/refractory multiple myeloma. Responders (stable disease or more) will continue to receive up to eight cycles total in the absence of further progressive disease. The dose of MLN9708 will be fixed at 4 mg given on days 1, 8 and 15. Dexamethasone will be administered at 40 mg (oral) on Days 1, 8, 15 of each 28 day cycle. Dexamethasone administered as 40 mg oral on Days 1, 8, 15 of each 28 day cycle. Three doses of bendamustine will be evaluated (Dose 1: 70 mg/m\^2, days 1 and 2; Dose 2: 80 mg/m\^2. days 1 and 2; and Dose 3: 90 mg/m\^2, days 1 and 2).
PHASE 1 DESIGN: A 3+3 design was employed. At each dose, three patients were initially evaluated. When no dose limiting toxicities were observed, the bendamustine dose will be increased.
PHASE 2 DESIGN: Design for Phase II portion of study: The MTD or a recommended phase 2 dose (RP2D) for the combination. The plan is to treat additional patients at that dose to assess efficacy and response to treatment. The investigators plan to enroll 19 patients (including those treated at the MTD in Phase I).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 38
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description MLN9708, Bendamustine and Dexamethasone MTD Bendamustine (MTD) Ixazomib 4 mg, days 1, 8, 15. Dexamethasone 40 mg oral weekly. Bendamustine dose levels: MTD given on days 1 and 2 MLN9708, Bendamustine and Dexamethasone Dose Escalation Bendamustine (multiple dose levels) Ixazomib 4 mg, days 1, 8, 15. Dexamethasone 40 mg oral weekly. Bendamustine dose levels: 70 mg/m\^2, 80mg/m\^2, or 90 mg/m\^2 given on days 1 and 2 MLN9708, Bendamustine and Dexamethasone MTD MLN9708 Ixazomib 4 mg, days 1, 8, 15. Dexamethasone 40 mg oral weekly. Bendamustine dose levels: MTD given on days 1 and 2 MLN9708, Bendamustine and Dexamethasone Dose Escalation MLN9708 Ixazomib 4 mg, days 1, 8, 15. Dexamethasone 40 mg oral weekly. Bendamustine dose levels: 70 mg/m\^2, 80mg/m\^2, or 90 mg/m\^2 given on days 1 and 2 MLN9708, Bendamustine and Dexamethasone Dose Escalation Dexamethasone Ixazomib 4 mg, days 1, 8, 15. Dexamethasone 40 mg oral weekly. Bendamustine dose levels: 70 mg/m\^2, 80mg/m\^2, or 90 mg/m\^2 given on days 1 and 2 MLN9708, Bendamustine and Dexamethasone MTD Dexamethasone Ixazomib 4 mg, days 1, 8, 15. Dexamethasone 40 mg oral weekly. Bendamustine dose levels: MTD given on days 1 and 2
- Primary Outcome Measures
Name Time Method Maximum Tolerated Dose of Bendamustine Six months for each dosing cohort Maximum tolerated dose of bendamustine in combination with fixed doses of ixazomib (MLN9708) and dexamethasone will be determined from the incidence of dose limiting toxicities at each dosage.
Objective Response Rate 18 months Objective response rate was defined as the number of subjects achieving a complete response (CR) or partial response (PR) after at least four cycles of ixazomib (MLN9708) and bendamustine plus dexamethasone.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) 36 months Overall survival was determined as the average number of months subjects survived following enrollment.
Progression Free Survival (PFS) 18 months This measure is the number of months participants remain free from evidence of disease.
Cumulative Response Rates in Patients After Eight Cycles. 18 months Percentage of subject response rates at any point during the eight cycles.
Duration of Response (DoR) 36 months Median time in months participants maintain CR, PR or stable disease.
Number of Participants Experiencing Dose-Limiting Toxicity (DLT) Six months A 3+3 design was employed. At each dose, three patients were initially evaluated. If no dose limiting toxicities were observed, the bendamustine dose was increased; if one dose limiting toxicity is observed, three additional patients were treated at that dose. A dose at which 2 DLTs were observed in 3 or 6 patients were judged to be too toxic and the lower dose was defined as the maximally tolerated dose (MTD).
Trial Locations
- Locations (1)
Froedtert Hospital and the Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States