A Study of Carfilzomib, Lenalidomide, Vorinostat, and Dexamethasone in Relapsed and/or Refractory Multiple Myeloma (QUAD)
|Multiple Myeloma||Drug: Vorinostat, Lenalidomide, Carfilzomib, Dexamethasone||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of Carfilzomib, Lenalidomide, Vorinostat, and Dexamethasone in Relapsed and/or Refractory Multiple Myeloma|
- Safety and dose of carfilzomib, lenalidomide, vorinostat and dexamethasone for MM [ Time Frame: 12 months ]
Primary Objective: To evaluate safety and establish the maximum tolerated dose (MTD) [and/or a protocol defined dose below the MTD] of carfilzomib, lenalidomide, vorinostat and dexamethasone in relapsed and/or refractory multiple myeloma subjects.
Secondary Objectives: To observe evidence of efficacy (response rate, duration of response, time to progression, time to next treatment)
- Overall response rate (ORR) Time to next treatment (TTNT) Time to progression (TTP) Duration of response (DOR [ Time Frame: 12 Months ]Secondary Objectives: To observe evidence of efficacy (response rate, duration of response, time to progression, time to next treatment)
|Study Start Date:||April 2011|
|Estimated Study Completion Date:||August 2015|
|Estimated Primary Completion Date:||August 2015 (Final data collection date for primary outcome measure)|
Experimental: carfilzomib for MML
Vorinostat, Lenalidomide, Carfilzomib, Dexamethasone - This study will be conducted as an open-label Phase I/II, single-center study in which subjects will receive carfilzomib, lenalidomide, vorinostat and dexamethasone, for relapsed and/or refractory multiple myeloma. Study treatment will be administered in sequential cohorts, with 3-6 subjects in each cohort. Treatment will be administered in 28-day cycles, with the fourth week as a rest week, for 12 cycles or until disease progression or unacceptable toxicity develops.
Drug: Vorinostat, Lenalidomide, Carfilzomib, Dexamethasone
Dose Escalation Schema Cohort Carfilzomib (mg/m2) Lenalidomide (mg) Vorinostat (mg) Dexamethasone (mg)
Phase I/II studies of the novel proteasome inhibitor, carfilzomib, have shown it to have significant activity in patients with advanced multiple myeloma, including patients with bortezomib refractory disease. This drug, unlike bortezomib, has minimal neurotoxicity and appears to have minimal gastrointestinal (GI) toxicity. Experience with the combination of bortezomib, lenalidomide and dexamethasone has shown both neuropathy and chronic diarrhea to be limiting.
Vorinostat is a histone deacetylase inhibitor with modest single agent activity in multiple myeloma. Dysesthesia, GI issues and fatigue have been problematic in this patient population. More recent studies combining vorinostat with lenalidomide and dexamethasone or with bortezomib have demonstrated a much more robust activity, including in patients refractory to lenalidomide or bortezomib-based combinations. Again, neuropathy, fatigue and GI issues have been problematic.
The investigators own anecdotal experience with combinations of proteasome inhibitor, histone deacetylase inhibitor, immunomodulators and dexamethasone has shown this combination to be extremely active and well tolerated. The combination of vorinostat, carfilzomib, lenalidomide and dexamethasone should offer the opportunity to maximize activity while limiting toxicities, particularly neuropathy and GI.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01297764
|Contact: Palka Anand, RN||201-336-3040||PAnand@humed.com|
|Contact: Laura J McBride, RN, BSN, OCN||201-336-8020||Lmcbride@humed.com|
|United States, New Jersey|
|Hackensack University Medical Center||Recruiting|
|Hackensack, New Jersey, United States, 07601|
|Contact: Laura McBride, RN 201-336-8054 LMcBride@humed.com|
|Contact: Palka Anand, RN 201-996-3040 PAnand@humed.com|
|Principal Investigator:||David Siegel, MD, PhD||Hackensack University Medical Center|