Study of ACY-1215 in Combination With Lenalidomide, and Dexamethasone in Multiple Myeloma
|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:||December 2017|
|Primary Completion Date:||March 2016 (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
This is phase 1, single-arm, multicenter, open-label study in patients with relapsed or relapsed/refractory MM. The study employs a sequential group dose-escalation design to determine the DLT and MTD of ACY-1215 in combination with lenalidomide and dexamethasone, all administered orally (PO). The safety, tolerability, single- and multiple-dose PK, pharmacodynamics, and anti-tumor activity of ACY 1215 in combination with lenalidomide and dexamethasone also will be evaluated.
Each cohort will enroll 3 patients. Study drug doses will be escalated sequentially after the Safety Review Committee (SRC) reviews safety data collected in C1 (28 days) from patients enrolled at the current dose level as well as emerging data from ongoing studies of ACY-1215. If there are no DLTs (as defined in Section 5.2.6) during C1 or concerns based on data from other ongoing studies, the study will proceed with dose escalation to the next cohort following safety data review by the SRC. If 1 of 3 patients has a DLT, then up to 3 additional patients will be enrolled in that cohort; if none of the additional 3 patients experience a DLT during C1, escalation may then continue to the next cohort following SRC review. If 2 or more patients have DLTs during C1, the DLT dose level will have been reached.
The MTD is defined as the dose level immediately below the DLT dose level. A total of up to 6 additional patients may be enrolled at the MTD or other appropriate dose level to obtain additional AE, PK, pharmacodynamic, and anti-tumor activity data on ACY 1215 in combination with lenalidomide and dexamethasone.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01583283
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Dana Farber Cancer Institute|
|Boston, Massachusetts, United States, 02215|
|United States, North Carolina|
|UNC Lineberger Comprehensive Cancer Center|
|Chapel Hill, North Carolina, United States, 27599-7305|
|United States, Tennessee|
|Sarah Cannon Research Institute|
|Nashville, Tennessee, United States, 37203|
|United States, Washington|
|Fred Hutchinson Cancer Research Institute|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||Noopur Raje, MD||Massachusetts General Hospital|