The aim of this phase I/II trial is to determine the maximal tolerated dose (MTD) of carfilzomib together with pegylated liposomal doxorubicin hydrochloride (PLD) with or without dexamethasone, and then to establish the efficacy and safety of this novel combination in patients with relapsed or refractory multiple myeloma
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Washington University School of Medicine
St Louis, Missouri, United States
Maximum Tolerated Dose (MTD) of Carfilzomib and Pegylated Liposomal Doxorubicin (Phase I - Part 1).
* MTD is the maximum tolerated dose level tested unless dose limiting toxicity (DLT) are observed during Cycle 1. If DLT is observed, MTD will be the next lower dose level. * Please note that the maximum tolerated dose of carfilzomib and pegylated liposomal doxorubicin was not reached. The data below is the recommended dosage for further studies.
Time frame: 28 days (completion of first cycle of all Phase I - Part 1 patients)
Maximum Tolerated Dose (MTD) of Carfilzomib and PLD (Phase I - Part 2).
-MTD is the maximum tolerated dose level tested unless dose limiting toxicity (DLT) are observed during Cycle 1. If DLT is observed, MTD will be the next lower dose level.
Time frame: 28 days (completion of first cycle of all Phase I - Part 2 patients)
Maximum Tolerated Dose (MTD) of Dexamethasone (Phase I - Part 2).
-MTD is the maximum tolerated dose level tested unless dose limiting toxicity (DLT) are observed during Cycle 1. If DLT is observed, MTD will be the next lower dose level.
Time frame: 28 days (completion of first cycle of all Phase I - Part 2 patients)
Phase 2 - Efficacy of Carfilzomib in Combination With PLD and Dexamethasone as Measured by the Percentage of Participants With Confirmed Tumor Responses
-A confirmed response is defined to be a complete response (CR), very good partial response (VGPR), or partial response (PR) per IMWG Criteria.
Time frame: Completion of treatment (median number of cycles was 9.5 (range 1-34))
Phase 2 - Toxicity of Carfilzomib in Combination With PLD and Dexamethasone as Measured by Number of Participants Who Experience Grade 3/4 Toxicity
Time frame: Through 30 days after completion of treatment (median number of cycles was 9.5 (range 1-34))
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Median Overall Survival
Time frame: Completion of follow-up (median of 23.3 months)
Progression-free Survival Time (Phase 2 Only)
-Progression per IMWG Criteria
Time frame: Through completion of follow-up (median follow-up was 23.3 months)
Median Duration of Overall Response
* For participants with confirmed tumor responses * A confirmed response is defined to be a complete response (CR), very good partial response (VGPR), or partial response (PR) per IMWG Criteria
Time frame: Through completion of follow-up (median follow-up was 23.3 months)