Carfilzomib, Pomalidomide, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Multicenter, Open-label, Single-arm, Phase 1b/2 Study of the Safety and Efficacy of Combination Treatment With Pomalidomide, Dexamethasone, and Carfilzomib (PdC) in Subjects With Relapsed and Relapsed/Refractory Multiple Myeloma|
- MTD of carfilzomib when administered in combination with fixed dosing pomalidomide and dexamethasone [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
- Partial response rate after 4 courses according to IMW criteria [ Time Frame: 4 months ] [ Designated as safety issue: No ]The proportion and exact 95% binomial confidence interval for the response rate will be reported adjusted for the two-stage design of this trial.
- Overall response rate [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Defined as at least a partial response to therapy, will be reported along with its exact 95% binomial confidence
- Time to progression [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Estimated using the product-limit method of Kaplan and Meier.
- Duration of response [ Time Frame: From the date of the clinical examination which confirmed the response, until the date of disease progression, or censoring at the date of last clinical follow-up up to 2 years ] [ Designated as safety issue: No ]Assessed conditional upon achieving at least a partial response.
- Progression-free survival [ Time Frame: From the date of first therapy until the date of documented disease progression or death up to 2 years ] [ Designated as safety issue: No ]Estimated using the product-limit method of Kaplan and Meier.
- Overall survival [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Estimated using the product-limit method of Kaplan and Meier.
|Study Start Date:||August 2012|
|Estimated Study Completion Date:||December 2017|
|Estimated Primary Completion Date:||August 2017 (Final data collection date for primary outcome measure)|
Experimental: Carfilzomib, pomalidomide, dexamethasone)
Patients receive carfilzomib, pomalidomide, and dexamethasone at indicated doses and schedule every 28 days. Patients may continue to receive treatment in the absence of disease progression or unacceptable toxicity.
Other Name: CC-4047Drug: carfilzomib
Other Names:Drug: dexamethasone
Given PO or IV
I. To determine the maximally tolerated dose (MTD) of carfilzomib when administered in combination with fixed dosing pomalidomide and dexamethasone in patients with relapsed and relapsed/refractory multiple myeloma.
II. To determine the efficacy of the combination regimen at the MTD as measured by partial response (PR) response rate defined as per International Myeloma Working Group (IMW) criteria.
I. To determine the best stringent complete response (sCR)/CR/nodular complete response (nCR) and >= very good partial response (VGPR) rates.
II. To estimate the time on study (TOS), duration of response (DOR), time to progression (TTP), progression-free survival (PFS), and overall survival (OS) distributions.
III. To further define the toxicity at the MTD.
I. To perform an analysis of a subset of patients who are refractory to either pomalidomide or carfilzomib or lenalidomide, bortezomib, and dexamethasone (RVD) combination.
II. To evaluate the status of minimal residual disease (MRD) in patient who achieve sCR, CR or nCR.
III. To evaluate prognostic markers and markers of response to pomalidomide, dexamethasone, and carfilzomib (PdC) in patients refractory to lenalidomide by analyzing pre-treatment clinical covariates and pre-treatment plasma cell profiles by proteomics and gene expression profiling (GEP).
OUTLINE: This is a phase I dose-escalation study of carfilzomib followed by phase II.
Patients receive carfilzomib intravenously (IV) over 30 minutes on days 1, 2, 8, 9, 15 and 16, pomalidomide orally (PO) once daily (QD) on days 1-21, and dexamethasone PO or IV on days 1, 8, 15, and 22. Treatment repeats every 28 days for at least 8 courses in the absence of disease progression or unacceptable toxicity. Patients achieving stable disease may continue to receive treatment in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 28 days and then every 3 months for up to 2 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01665794
|United States, Illinois|
|University of Chicago Comprehensive Cancer Center||Recruiting|
|Chicago, Illinois, United States, 60637-1470|
|Contact: Andrzej J. Jakubowiak 773-834-1592 email@example.com|
|Principal Investigator: Andrzej J. Jakubowiak|
|United States, New Jersey|
|Hackensack University Medical Center||Not yet recruiting|
|Hackensack, New Jersey, United States, 07601|
|Contact: David S. Siegel 201-336-8704 firstname.lastname@example.org|
|Principal Investigator: David S. Siegel|
|Principal Investigator:||Andrzej Jakubowiak||University of Chicago Comprehensive Cancer Center|