Study of ACY-1215 in Combination With Lenalidomide, and Dexamethasone in Multiple Myeloma
The purpose of this study is to determine the best dose of ACY-1215 in combination with lenalidomide and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma. Once determined, the purpose of this study will be to determine the efficacy of ACY-1215 in combination with lenalidomide and dexamethasone in patients with relapsed multiple myeloma who have had 1-3 prior therapies and who are not lenalidomide-refractory.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II, Open Label, Multicenter Study of ACY-1215 in Combination With Lenalidomide and Dexamethasone for the Treatment of Relapsed or Relapsed/Refractory Multiple Myeloma|
- Establish optimal dose of ACY-1215 in combination with lenalidomide and dexamethasone [ Time Frame: Upon completion of a 28 day treatment cycle ] [ Designated as safety issue: Yes ]
Determine maximum tolerated dose (MTD) of combination therapy. Patients will be assessed for dose-limiting toxicities (DLT) at each visit during Cycle 1.
During the second part of the study, investigate efficacy of the dose determined during the first part of the study by objective response rate and progression-free survival.
- Evaluate safety by assessing toxicities [ Time Frame: Upon completion of a 28 day treatment cycle ] [ Designated as safety issue: Yes ]Evaluate safety by assessing possible toxicities of thrombocytopenia, neutropenia, serum creatinine, total bilirubin, diarrhea, and/or vomiting.
- Determine the preliminary anti-tumor activity of ACY-1215 in combination with lenalidomide and dexamethasone [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: Yes ]Change in M-protein (baseline to the end of each 28 day cycle, up to 24 weeks), objective response rate assessed according to the IMWG criteria (baseline, every other day 15 of each cycle, up to 24 weeks).
- Area under the plasma concentration versus time curve (AUC) [ Time Frame: Upon completion of a 28 day cycle. ] [ Designated as safety issue: No ]AUC of ACY-1215 and lenalidomide
- Changes in acetylated tubulin and acetylated histone levels [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]Evaluation of changes in acetylated tubulin(blood and bone marrow)and acetylated histones (blood and bone marrow)at baseline and post-treatment (Day 1 and up to week 24)
|Study Start Date:||April 2012|
|Estimated Study Completion Date:||October 2014|
|Estimated Primary Completion Date:||October 2014 (Final data collection date for primary outcome measure)|
Experimental: ACY-1215, Lenalidomide and dexamethasone
Open label dosing cohorts will evaluate oral ACY-1215 (doses ranging from 40 - 480 mg days 1-5, 8-12, 15-19) in combination with oral Lenalidomide (doses ranging from 15 - 25 mg days 1-21) and oral dexamethasone (40 mg once weekly).
Dose escalation up to 480 mg administered orally on Days 1-5, 8-12 and 15-19 of a 28 day dosing schedule.
Other Name: Histone deacetylase inhibitorDrug: lenalidomide
Dosed on Days 1-21 of a 28 day cycle.
Other Name: RevlimidDrug: Dexamethasone
Dosed on Days 1, 8, 15 and 22 of a 28 day treatment cycle.
Other Name: steroid
|Contact: Gretchen Patrickfirstname.lastname@example.org|
|United States, Massachusetts|
|Massachusetts General Hospital||Recruiting|
|Boston, Massachusetts, United States, 02114|
|Contact: Nicole Couture 617-724-2689 email@example.com|
|Principal Investigator: Andrew Yee, MD|
|United States, North Carolina|
|UNC Lineberger Comprehensive Cancer Center||Recruiting|
|Chapel Hill, North Carolina, United States, 27599-7305|
|Contact: Elizabeth Tita, RN, BSN 919-843-7657 firstname.lastname@example.org|
|Principal Investigator: Peter Voorhees, MD|
|United States, Tennessee|
|Sarah Cannon Research Institute||Recruiting|
|Nashville, Tennessee, United States, 37203|
|Contact: Cindy Farley 615-329-7237 email@example.com|
|Principal Investigator: Jesus Berdeja, MD|
|United States, Washington|
|Fred Hutchinson Cancer Research Institute||Recruiting|
|Seattle, Washington, United States, 98109|
|Contact: Cari Morin 206-667-6238 firstname.lastname@example.org|
|Principal Investigator: William Bensinger, MD|
|Principal Investigator:||Noopur Raje, MD||Massachusetts General Hospital|