Pomalidomide in Gene Expression Profiling (GEP)-Defined High-risk Multiple Myeloma
This is a phase II study, open-label, single institution trial of pomalidomide in GEP-defined, high-risk relapsing/refractory multiple myeloma. Prior therapy must have included lenalidomide. Patient accrual is 30 over a 2 year period.
- To determine progression-free survival (PFS) after initiation of pomalidomide therapy
- To determine the response rate (CR, n-CR, VGPR) and duration of response after pomalidomide therapy.
- To determine gene expression profiling (GEP) changes exerted within 48 hours of initiation of daily pomalidomide dosing.
- To determine gene expression profiling (GEP) changes exerted within 48 hours of initiation 3 concurrent days of exposure to lenalidomide.
- To determine MRI- and PET-CT-defined CR in studies obtained at baseline and every 6 month examinations.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Trial of Pomalidomide in GEP-defined High-risk Multiple Myeloma That is Relapsing or Refractory to Prior Therapy|
- Progression-free Survival (PFS) After Initiation of Pomalidomide Therapy [ Time Frame: 1 year following initiation of pomalidomide therapy ]Progression -free survival (PFS) after initiation of pomalidomide therapy. Progressive disease is defined as increase of > 25% from lowest response value in any one or more of the following: Serum M-component and/or (the absolute increase must be > 0.5 g/dL); Urine M-component and/or (the absolute increase must be > 200 mg/24 h); Only in patients without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels. The absolute increase must be > 10 mg/dL; Bone marrow plasma cell percentage; the absolute percentage must be > 10%; Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcaemia (corrected serum calcium > 11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder.
- Response Rate (CR, n-CR, VGPR) and Duration of Response After Pomalidomide Therapy. [ Time Frame: 1 year following initiation of pomalidomide therapy ]Response rate (CR, n-CR, VGPR) Duration of response rate after initiation of pomalidomide therapy
- Gene Expression Profiling (GEP) Changes Exerted Within 48 Hours of Initiation of Daily Pomalidomide Dosing. [ Time Frame: 48 hours ]Gene expression profiling at baseline and at 48 hours after initiation of pomalidomide
- Gene Expression Profiling (GEP) Changes Exerted Within 48 Hours of Initiation 3 Concurrent Days of Exposure to Lenalidomide. [ Time Frame: 48 hours ]Gene expression profiling at 48 hours after initiation of lenalidomide
|Study Start Date:||October 2011|
|Study Completion Date:||September 2013|
|Primary Completion Date:||September 2013 (Final data collection date for primary outcome measure)|
Only enough CC-4047 for 1 cycle of therapy may be provided to the patient each cycle. Participants will receive CC-4047 4 mg/day for 21 days, every 28 days. Treatment will continue until disease recurrence or untoward toxicity.
Other Name: CC-4047
Pomalidomide is a 2nd generation immunomodulatory agent (IMiD®) with greater efficacy than lenalidomide and with a similar toxicity spectrum. Phase I trials have shown that pomalidomide 1 to 5 mg is well-tolerated1,2.
TT3 has been remarkably successful in the management of newly diagnosed MM, inducing CR rates of >60% and 4-year estimates of overall and event-free survival of 85% and 75%. Of those achieving CR, estimated 4-year CR rate is 85%. TT3 maintenance has been with either VTD in 2003-33 or VRD in 2006-66, so that pomalidomide's role in overcoming refractoriness to lenalidomide can be assessed.
Pharmacogenomic investigations comparing GEP data obtained at baseline and 48hr post-treatment have been performed in case of thalidomide, dexamethasone, lenalidomide, bortezomib and melphalan3. Thus, as most patients on TT3 had baseline and 48-hr GEP investigations performed after bortezomib, the opportunity exists to investigate, at the time of relapse, not only a re-challenge with bortezomib with 48hr GEP but also pomalidomide's effect.
This is a phase II study, open-label, single institution trial of pomalidomide in GEP-defined, high-risk relapsing/refractory multiple myeloma. Prior therapy must have included lenalidomide.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01177735
|United States, Arkansas|
|University of Arkansas for Medical Sciences, Myeloma Institute for Research and Therapy|
|Little Rock, Arkansas, United States, 72205|
|Principal Investigator:||Saad Usmani, MD||University of Arkansas for Medical Sciences, Myeloma Institute for Research and Therapy|