A Multi-Center Phase I/II, Open-Label, Dose-Finding Pilot Study of the Combination of Carfilzomib and Pomalidomide With Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma
Overview
- Phase
- Phase 1
- Intervention
- Carfilzomib
- Conditions
- Multiple Myeloma
- Sponsor
- Criterium, Inc.
- Enrollment
- 136
- Locations
- 9
- Primary Endpoint
- Adverse Events as a Measure of Safety and Tolerability
- Status
- Terminated
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a dose finding pilot study to evaluate the safety and determine the maximum tolerated dose of the combination of carfilzomib and pomalidomide with dexamethasone (CPD) in patients with relapsed or refractory multiple myeloma followed by a phase II expansion at the MTD to evaluate efficacy.
Detailed Description
This is a dose finding pilot study to evaluate the safety and determine the maximum tolerated dose of the combination of carfilzomib and pomalidomide with dexamethasone (CPD) in patients with relapsed or refractory multiple myeloma followed by a phase II expansion at the MTD to evaluate efficacy. The study will explore the efficacy of CPD including overall response, time to progression, progression free survival, and time to next therapy.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Cytopathologically or histologically confirmed dx of multiple myeloma
- •Relapsed or refractory to the most recently received therapy.
- •All pts must have received prior lenalidomide therapy and been determined to be refractory, relapsed, or intolerant.
- •Measurable disease, as indicated by one or more of the following:
- •Serum M-protein ≥ 0.5 g/dL Urine Bence Jones protein ≥ 200 mg/24 hr Elevated Free Light Chain as per IMWG criteria, and abnormal ratio
- •Pts must be ≥ 18 years of age
- •Life expectancy of more than 3 months
- •ECOG PS of 0-2
- •Adequate hepatic function, with bilirubin \< 2 times the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3 times ULN
- •Uric acid must be within laboratory normal range
Exclusion Criteria
- •Pts with known sensitivity to any immunomodulatory drugs (IMiDs)
- •Use of any other experimental drug or therapy within 21 days prior to first dose
- •Exposure to any prior chemotherapy, steroid use, or other myeloma treatment within 14 days prior to first dose. Pts currently on long term steroids do not require any washout period. in addition, steroid use for spinal cord compression is permitted and does not require a washout period.
- •Radiation therapy within 14 days prior to first dose
- •Known allergies to carfilzomib or Captisol
- •POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- •Current diagnosis of plasma cell leukemia
- •Waldenström's macroglobulinemia
- •Major surgery within 21 days prior to first dose
- •Pregnant or lactating females
Arms & Interventions
Carfilzomib, Pomalidomide, Dexamethasone
All eligible subjects will receive the study intervention of Carfilzomib, Pomalidomide, and Dexamethasone.
Intervention: Carfilzomib
Carfilzomib, Pomalidomide, Dexamethasone
All eligible subjects will receive the study intervention of Carfilzomib, Pomalidomide, and Dexamethasone.
Intervention: Pomalidomide
Carfilzomib, Pomalidomide, Dexamethasone
All eligible subjects will receive the study intervention of Carfilzomib, Pomalidomide, and Dexamethasone.
Intervention: Dexamethasone
Outcomes
Primary Outcomes
Adverse Events as a Measure of Safety and Tolerability
Time Frame: Throughout treatment, estimated at 2-12 months per patient
Review of adverse events for safety and to determine the maximum tolerated dose of the combination treatment.
Overall Response in Phase II
Time Frame: Every 28 days while on treatment (estimated at 2- 12 months per patient)
Overall Response (SD, MR, PR, VGPR, CR, sCR)
Secondary Outcomes
- Overall Response in Phase I(Every 28 days while on treatment (estimated at 2- 12 months per patient))
- Time to Progression(Every 28 days while on treatment (estimated at 2-12 months per patient))
- Progression Free Survival(throughout follow up (every 2-3 months for 2 years))
- Time to next therapy(throughout follow up (every 2-3 months for 2 years))