S1304, Carfilzomib and Dexamethasone for Treating Patients With Relapsed or Refractory Myeloma
|ClinicalTrials.gov Identifier: NCT01903811|
Recruitment Status : Active, not recruiting
First Posted : July 19, 2013
Last Update Posted : March 7, 2018
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Plasma Cell Myeloma Refractory Plasma Cell Myeloma||Drug: Carfilzomib Drug: Dexamethasone Other: Laboratory Biomarker Analysis||Phase 2|
I. To evaluate and compare progression free survival (PFS) of two different doses of carfilzomib with dexamethasone in multiple myeloma (MM) patients with relapsed and/or refractory disease.
I. To evaluate and compare response rates (RR) for each arm. II. To evaluate response rates (RR) for patients that relapse on low dose carfilzomib and subsequently cross-over to high dose carfilzomib.
III. To evaluate the safety of this combination for this patient population. IV. To evaluate overall survival (OS).
I. To explore the molecular variability in MM cells obtained from extramedullary bone marrow relapse sites.
II. To explore the role of positron emission tomography (PET) scanning in assessing disease burden and as a tool to assess treatment response.
III. To explore changes in left ventricular ejection fraction (LVEF) in patients with relapsed or refractory multiple myeloma treated with low dose carfilzomib or high dose carfilzomib plus dexamethasone.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive dexamethasone intravenously (IV) and low-dose carfilzomib IV over 2-10 minutes on days 1, 2, 8, 9, 15, and 16. Patients with progression cross-over to Arm II.
ARM II: Patients receive dexamethasone IV and high-dose carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16.
Note that for the first course of treatment on both arms carfilzomib is given at a reduced rate to assess toxicity.
In both arms, treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 3 years from initial registration.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||143 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Randomized Study Comparing Two Doses of Carfilzomib (NSC-756640) With Dexamethasone for Multiple Myeloma Patients With Relapsed or Refractory Disease|
|Study Start Date :||October 2013|
|Actual Primary Completion Date :||November 2017|
|Estimated Study Completion Date :||July 2019|
Experimental: Arm I (dexamethasone, low-dose carfilzomib)
Patients receive dexamethasone IV and low-dose carfilzomib IV over 2-10 minutes on days 1, 2, 8, 9, 15, and 16. (Note that course 1 is given at a reduced dose.) Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients with progression cross-over to Arm II.
Other: Laboratory Biomarker Analysis
Experimental: Arm II (dexamethasone, high-dose carfilzomib)
Patients receive dexamethasone IV and high-dose carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16. (Note that course 1 is given at a reduced dose over 2-10 minutes.) Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
- Progression-free survival [ Time Frame: From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 2 years ]Assessed in each arm using the method of Kaplan Meier and compared between arms using the stratified long-rank test.
- Overall survival [ Time Frame: Up to 3 years ]Assessed in each arm using the method of Kaplan Meier and compared between arms using the stratified log-rank test.
- Response rate (stringent complete response [sCR], complete response [CR], very good partial response [VGPR], partial response [PR]) [ Time Frame: Up to 3 years ]Assessed in each arm and compared between arms using Fisher's exact test.
- Gene expression profiles [ Time Frame: Up to 3 years ]Bone marrow compared to that of an aspirate taken at the site of the EMP. Data will be log-transformed before analysis. Exploratory analyses will examine underlying distributions using boxplots, density plots, scatter plots, etc. For differential expression analysis of the two sample types t-tests will be conducted on genes. False discovery rate will be used to control the average false positive proportions among selected genes. Genes will be ranked by their q-value and pathway analysis conducted upon selected genes to determine biological plausibility and relevance to molecular functionality.
- Incidence of CR by PET, defined as the disappearance of all focal lesions and the resolution of EMD [ Time Frame: Up to week 45 ]Univariate and multivariate logistic regression will be used to determine the impact of biochemical CR on CR by PET. In the multivariate analysis adjustment for standard prognostic factors such as age, albumin, beta-2 microglobulin, serum creatinine, c-reactive protein and lactate dehydrogenase will be included.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01903811
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|Principal Investigator:||Sikander Ailawadhi||Southwest Oncology Group|