A Study of Weekly Carfilzomib in Combination With Dexamethasone for Progressive Multiple Myeloma
This is a Phase 1/2, multicenter, single-arm, nonrandomized, open-label and dose-escalation study of weekly carfilzomib and dexamethasone (Cd-qw) for patients with progressive multiple myeloma. The Phase 1 dose escalation portion will enroll patients into sequential dose-escalating cohorts consisting of 3 patients each to establish the maximum tolerated dose (MTD) of carfilzomib administered weekly as a 30 minute intravenous (IV) infusion with dexamethasone. The Phase 2 portion will enroll patients using the MTD established for carfilzomib from the Phase 1 portion of the study. Dexamethasone will be administered IV or PO at the same dose and schedule as used in the Phase 1 portion of the study.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1/2, Multicenter, Single-arm, Nonrandomized, Open-label and Dose-escalation Study of Weekly Carfilzomib and Dexamethasone (Cd-qw) for Patients With Progressive Multiple Myeloma.|
- Phase 1: Determine the Maximum Tolerated Dose [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]Phase 1: Determine the MTD for patients with progressive multiple myeloma treated with weekly carfilzomib and dexamethasone.
- Phase 2: Overall Response Rate [ Time Frame: 18 months ] [ Designated as safety issue: No ]Phase 2: Estimate the overall response rate (ORR, defined as the proportion of patients who achieve a confirmed PR or better) for patients with progressive multiple myeloma treated with weekly carfilzomib and dexamethasone.
- Clinical Benefit Response Rate [ Time Frame: 18 months ] [ Designated as safety issue: No ]Estimate the clinical benefit response rate (CBR) in accordance with IMWG Criteria
- Progression Free Survival [ Time Frame: 18 months ] [ Designated as safety issue: No ]Estimate the progression-free survival (PFS)
- Time To Progression [ Time Frame: 18 months ] [ Designated as safety issue: No ]Estimate the time to progression (TTP)
- Duration of Response [ Time Frame: 18 months ] [ Designated as safety issue: No ]Estimate the duration of response (DOR)
|Study Start Date:||July 2012|
|Estimated Study Completion Date:||July 2015|
|Estimated Primary Completion Date:||July 2014 (Final data collection date for primary outcome measure)|
Phase 1: Carfilzomib will be administered as a 30-minute intravenous (IV) infusion on Days 1, 8, and 15 of each 28-day cycle. On only Day 1 of Cycle 1, all patients will receive carfilzomib at 20 mg/m2. All subsequent carfilzomib doses (45, 56, 70 or 88 mg/m2) will be administered according to the dose assignment for each cohort.
Phase 2: using the MTD established for carfilzomib from the Phase 1 portion of the study (except on Cycle 1 Day 1 the carfilzomib dose will be 20 mg/m2); this arm will be administered drug on the same schedule as in Phase 1.
This Phase 1/2 study in patients with progressive multiple myeloma is designed to achieve the following: to determine the MTD of carfilzomib and dexamethasone administered once weekly (Cd-qw) for 3 consecutive weeks in a 28-day cycle and to determine the magnitude of responses achieved in patients treated with the MTD.
The Cd-qw dosing schedule proposed in this protocol may be beneficial from a patient convenience perspective compared to the twice-weekly dosing schedule, however, as the clinical benefit and safety of weekly carfilzomib administration has not been assessed in multiple myeloma patients, patients who progress on weekly carfilzomib will be allowed 1 attempt to recapture response by increasing the dose frequency to the twice-weekly carfilzomib dosing schedule that has demonstrated efficacy and tolerability. This information will be valuable in assessing the dose intensity impact on the suppression of multiple myeloma in the relapsed setting.
Finally, this protocol will eliminate the requirement for fluid administration with carfilzomib after Cycle 1 and will reduce the time that is required to treat the patient in clinic. This modification will be studied for its effect on the carfilzomib safety profile.
|Contact: Onyx Medical Information||877-ONYX-121 (877-669-9121)||firstname.lastname@example.org|
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|Study Director:||Priti Patel, MD||Onyx Therapeutics Medical Monitor|