Study of ACY-1215 in Combination With Lenalidomide, and Dexamethasone in Multiple Myeloma
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|ClinicalTrials.gov Identifier: NCT01583283|
Recruitment Status : Active, not recruiting
First Posted : April 24, 2012
Last Update Posted : April 23, 2019
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma||Drug: ACY-1215 Drug: lenalidomide Drug: Dexamethasone||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||38 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||July 12, 2012|
|Estimated Primary Completion Date :||December 31, 2019|
|Estimated Study Completion Date :||December 31, 2019|
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 inhibitor
Dosed on Days 1-21 of a 28 day cycle.
Other Name: Revlimid
Dosed on Days 1, 8, 15 and 22 of a 28 day treatment cycle.
Other Name: steroid
- To determine DLT of ACY-1215 administered in combination with lenalidomide and dexamethasone in patient with relapsed/refractory MM [ Time Frame: up to 7 years ]Number of participants with Dose Limiting Toxicity (DLT)
- To determine MTD of ACY-1215 administered in combination with lenalidomide and dexamethasone in patient with relapsed/refractory MM [ Time Frame: up to 7 years ]Maximum Tolerated Dose is defined as the dose level immediately below the DLT dose level.
- Objective Response Rate of ACY-1215 [ Time Frame: up to 7 years ]The objective response rate is the proportion of subjects achieving an investigator conformed partial response (PR) or better, to treatment according to IMWG (International Myeloma Working Group).
- Duration of Response [ Time Frame: Up to approximately 7 years ]The duration of response is defined as the time (in weeks) from the date of the first documentation of objective response to the first documentation of objective tumor progression or death on study due to any cause, whichever comes first.
- Adverse Events (AEs) [ Time Frame: From enrollment until at least 28 days after completion of study treatment ]Number of participants with adverse event
- Disease Control Rate [ Time Frame: Up to approximately 7 years ]Disease control rate is defined as the proportion of subjects with a response (Unconfirmed or Confirmed) of SD or better, more specifically sCR, CR, VGPR, PR, MR, or SD respectively.
- Progression-free Survival [ Time Frame: Up to approximately 7 years ]PFS is defined as the time (in weeks) from the date of first dose to the date of first documentation of disease progression or death on study due to any cause, whichever comes first.
- Evaluate the pharmacodynamics of ACY-1215 in combination with lenalidomide and dexamethasone in patients with relapsed or relapsed/refractory MM [ Time Frame: up to 28 days ]Exposure-response of ACY-1215 in combination with lenalidomide and dexamethasone, including biomarkers relating to intracellular protein acetylation, levels of proteins, messenger ribonucleic acid (mRNA) and microRNA expression profiles will be analyzed for potential relationships.
- Pharmacokinetic- Cmax [ Time Frame: up to 28 days ]Maximum serum concentration
- Pharmacokinetic- Cmin [ Time Frame: up to 28 days ]Minimum observed concentration
- Pharmacokinetic- Tmax [ Time Frame: up to 28 days ]Time to maximum serum concentration
- Pharmacokinetic- AUC [ Time Frame: up to 28 days ]Area under the plasma concentration time curve
- Pharmacokinetic- t1/2 [ Time Frame: up to 28 days ]Serum half-life
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01583283
|United States, Massachusetts|
|Dana Farber Cancer Institute|
|Boston, Massachusetts, United States, 02215|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 2114|
|United States, North Carolina|
|University of North Carolina|
|Chapel Hill, North Carolina, United States, 27599|
|United States, Tennessee|
|Sarah Cannon Research Institute Drug Development Unit|
|Nashville, Tennessee, United States, 37203|
|United States, Washington|
|Fred Hutchinson Cancer Research Center|
|Seattle, Washington, United States, 98109|
|Study Director:||Mary Garelik, MD||Celgene|