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Study of ACY-241 Alone and in Combination With Pomalidomide and Dexamethasone in Multiple Myeloma

Primary Purpose

Multiple Myeloma

Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
ACY-241
Pomalidomide
Dexamethasone
Sponsored by
Celgene
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

  • Must have a documented diagnosis of MM and have relapsed or relapsed-and-refractory disease. All patients must have relapsed after having achieved at least stable disease (SD) for at least 1 cycle of treatment to at least 1 prior regimen and then developed progressive disease (PD). Relapsed-and-refractory patients also have documented evidence of PD during or within 60 days of completing last treatment
  • Must have undergone prior treatment with at least 2 cycles of lenalidomide and at least 2 cycles of proteasome inhibitor unless not a candidate.
  • May have undergone prior treatment with pomalidomide if patient is not refractory to pomalidomide and has previously achieved a response of MR or better to pomalidomide.
  • Must have measurable disease (serum M-protein or urine M-protein).
  • Must have Eastern Cooperative Oncology Group (ECOG) Performance score of 0, 1, or 2.
  • Must be able to take low-dose aspirin, low molecular weight heparin, or other equivalent antithrombotic or anticoagulant daily as prophylactic anticoagulation.

Key Exclusion Criteria:

  • Prior therapy with pomalidomide with best response of PD or SD.
  • Prior therapy with histone deacetylase (HDAC) inhibitor.
  • Any of the following laboratory abnormalities: Absolute neutrophil count(ANC) < 1,000/µL, Platelet count < 75,000/µL or < 50,000/µL for patients in whom ≥ 50% of bone marrow nucleated cells are plasma cells, Hemoglobin < 8 g/dL, Creatinine clearance < 45 mL/min according to Cockcroft-Gault formula. If creatinine clearance calculated from the 24 hour urine sample is ≥ 45 mL/min, patient will qualify for the trial, Aspartate transaminase (AST) or Alanine transaminase (ALT) > 3.0 × Upper Limited Normal (ULN), Serum total bilirubin > 2.0 mg/dL or > 3.0 × ULN for patients with hereditary benign hyperbilirubinaemia.
  • Hematologic growth factors are not allowed at screening or during the first cycle of phase 1a or 1b.
  • Nonsecretory myeloma or free light chain detected in serum only (ogliosecretory).
  • Hypersensitivity to thalidomide, lenalidomide, pomalidomide, or dexamethasone
  • Patients who received an allogeneic bone marrow or allogeneic peripheral blood stem cell transplant less than 12 months prior to initiation of study

Sites / Locations

  • Local Institution - 109
  • Colorado Blood Cancer Institute
  • University of Miami Medical Center
  • Local Institution - 108
  • Local Institution - 103
  • Local Institution - 104
  • Local Institution - 105
  • Local Institution - 101
  • Gabrail Cancer Center Research
  • CTRC at The UT Health Science Center at San Antonio
  • Local Institution - 111
  • Local Institution - 340
  • Local Institution - 341
  • Local Institution - 330
  • Local Institution - 320
  • Local Institution - 301
  • Local Institution - 300

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ACY-241, Pomalidomide, and dexamethasone

Arm Description

Open label dosing cohorts will evaluate oral ACY-241 (dosing ranging from 180 mg to 480 mg days 1-21) in combination with oral pomalidomide (4 mg days 1-21), and oral dexamethasone (40 mg qd on days 1, 8, 15, 22).

Outcomes

Primary Outcome Measures

Maximum tolerated dose of ACY-241 as monotherapy as assessed by dose limiting toxicities
Maximum tolerated dose of ACY-241 in combination with pomalidomide and low dose dexamethasone as assessed by dose limiting toxicities
First cycle of combination therapy

Secondary Outcome Measures

Frequency and severity of AEs as measured by safety and tolerability
Single- and multiple-dose peak-plasma concentration
Single- and multiple-dose area under the plasma concentration versus time curve
Change in acetylation of histone and tubulin as a measure of pharmacodynamics
Change in fetal hemoglobin expression as a measure of pharmacodynamics
ACY-241 metabolite concentration in blood samples
Exposure response analyses of potential biomarkers of response.
Frequency and severity of AEs as measured by safety and tolerability in combination
Change in fetal hemoglobin expression as a measure of pharmacodynamics
Change in acetylation of histone and tubulin as a measure of pharmacodynamics
Single- and multiple-dose area under the plasma concentration versus time curve
Quantification of M-protein as a measure of anti-tumor activity

Full Information

First Posted
March 3, 2015
Last Updated
October 10, 2023
Sponsor
Celgene
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1. Study Identification

Unique Protocol Identification Number
NCT02400242
Brief Title
Study of ACY-241 Alone and in Combination With Pomalidomide and Dexamethasone in Multiple Myeloma
Official Title
A Phase 1a/1b Multicenter, Single-Arm, Open-Label, Dose-Escalation Study to Determine the Maximum Tolerated Dose, Safety, and Preliminary Activity of Oral ACY-241 Alone and in Combination With Pomalidomide and Low-Dose Dexamethasone in Patients With Relapsed or Relapsed-and-Refractory Multiple Myeloma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 7, 2015 (Actual)
Primary Completion Date
January 31, 2024 (Anticipated)
Study Completion Date
January 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celgene

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a phase 1a/1b, multicenter, single-arm, open-label, dose escalation study to determine the maximum tolerated dose (MTD) and evaluate the safety and preliminary antitumor activity of ACY-241 for oral administration as monotherapy and in combination therapy with orally administered pomalidomide and low-dose dexamethasone in eligible patients with relapsed or relapsed-and-refractory multiple myeloma (MM).
Detailed Description
During phase 1a, patients will receive 1 cycle of ACY-241 monotherapy. Patients who complete the ACY-241 monotherapy cycle without a dose limiting toxicity (DLT) and are clinically stable may continue to phase 1b combination therapy, beginning with Cycle 2. During phase 1b, patients will receive ACY 241 in combination with pomalidomide and low dose dexamethasone at the currently approved pomalidomide dose and schedule. Each cohort of patients in phase 1a and phase 1b will consist of at least 3 patients. The first patient enrolled in each cohort of phase 1a will be observed for 1 week before enrollment of subsequent patients in the cohort. Patients who withdraw consent before entering phase 1b will be replaced. (Replacement patients must complete phase 1a prior to continuing to phase 1b.) Patients who experience a DLT or other unacceptable toxicity in Cycle 1 of phase 1a monotherapy or Cycle 2, the first cycle of phase 1b combination therapy, will be removed from study treatment. An assessment of the safety of treatment will be completed by the Safety Review Committee (SRC) prior to dose-escalation.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
85 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ACY-241, Pomalidomide, and dexamethasone
Arm Type
Experimental
Arm Description
Open label dosing cohorts will evaluate oral ACY-241 (dosing ranging from 180 mg to 480 mg days 1-21) in combination with oral pomalidomide (4 mg days 1-21), and oral dexamethasone (40 mg qd on days 1, 8, 15, 22).
Intervention Type
Drug
Intervention Name(s)
ACY-241
Other Intervention Name(s)
Histone deacetylase inhibitor
Intervention Description
Dose escalation up to 480 mg administered orally on Days 1-21 of a 28 day cycle.
Intervention Type
Drug
Intervention Name(s)
Pomalidomide
Other Intervention Name(s)
immunomodulatory agent
Intervention Description
4 mg qd dosed on days 1-21 of a 28 day cycle
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Other Intervention Name(s)
corticosteriod
Intervention Description
40 mg qd on days 1, 8, 15, 22
Primary Outcome Measure Information:
Title
Maximum tolerated dose of ACY-241 as monotherapy as assessed by dose limiting toxicities
Time Frame
Cycle 1 (28 days)
Title
Maximum tolerated dose of ACY-241 in combination with pomalidomide and low dose dexamethasone as assessed by dose limiting toxicities
Description
First cycle of combination therapy
Time Frame
Cycle 2 (28 days)
Secondary Outcome Measure Information:
Title
Frequency and severity of AEs as measured by safety and tolerability
Time Frame
Cycle 1 (28 days)
Title
Single- and multiple-dose peak-plasma concentration
Time Frame
Cycle 1 days 1, 2, 15 and 16
Title
Single- and multiple-dose area under the plasma concentration versus time curve
Time Frame
Cycle 1 days 1, 2, 15 and 16
Title
Change in acetylation of histone and tubulin as a measure of pharmacodynamics
Time Frame
Cycles 1 days 1, 2, 15, 16 and 22
Title
Change in fetal hemoglobin expression as a measure of pharmacodynamics
Time Frame
Cycles 1 days 1, 2, 15, 16 and 22
Title
ACY-241 metabolite concentration in blood samples
Time Frame
Cycles 1 days 1, 2, 15, 16 and 22
Title
Exposure response analyses of potential biomarkers of response.
Time Frame
Cycles 1 days 1, 2, 15, 16 and 22
Title
Frequency and severity of AEs as measured by safety and tolerability in combination
Time Frame
Beginning at Cycle 2 (28 day cycle each) until end of treatment
Title
Change in fetal hemoglobin expression as a measure of pharmacodynamics
Time Frame
Cycle 2 days 1, 2, 15, 16 and 22
Title
Change in acetylation of histone and tubulin as a measure of pharmacodynamics
Time Frame
Cycle 2 days 1, 2, 15, 16 and 22
Title
Single- and multiple-dose area under the plasma concentration versus time curve
Time Frame
Cycle 2 days 1, 2, 15, and 16
Title
Quantification of M-protein as a measure of anti-tumor activity
Time Frame
Day 1 of each cycle beginning at Cycle 2

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Must have a documented diagnosis of MM and have relapsed or relapsed-and-refractory disease. All patients must have relapsed after having achieved at least stable disease (SD) for at least 1 cycle of treatment to at least 1 prior regimen and then developed progressive disease (PD). Relapsed-and-refractory patients also have documented evidence of PD during or within 60 days of completing last treatment Must have undergone prior treatment with at least 2 cycles of lenalidomide and at least 2 cycles of proteasome inhibitor unless not a candidate. May have undergone prior treatment with pomalidomide if patient is not refractory to pomalidomide and has previously achieved a response of MR or better to pomalidomide. Must have measurable disease (serum M-protein or urine M-protein). Must have Eastern Cooperative Oncology Group (ECOG) Performance score of 0, 1, or 2. Must be able to take low-dose aspirin, low molecular weight heparin, or other equivalent antithrombotic or anticoagulant daily as prophylactic anticoagulation. Key Exclusion Criteria: Prior therapy with pomalidomide with best response of PD or SD. Prior therapy with histone deacetylase (HDAC) inhibitor. Any of the following laboratory abnormalities: Absolute neutrophil count(ANC) < 1,000/µL, Platelet count < 75,000/µL or < 50,000/µL for patients in whom ≥ 50% of bone marrow nucleated cells are plasma cells, Hemoglobin < 8 g/dL, Creatinine clearance < 45 mL/min according to Cockcroft-Gault formula. If creatinine clearance calculated from the 24 hour urine sample is ≥ 45 mL/min, patient will qualify for the trial, Aspartate transaminase (AST) or Alanine transaminase (ALT) > 3.0 × Upper Limited Normal (ULN), Serum total bilirubin > 2.0 mg/dL or > 3.0 × ULN for patients with hereditary benign hyperbilirubinaemia. Hematologic growth factors are not allowed at screening or during the first cycle of phase 1a or 1b. Nonsecretory myeloma or free light chain detected in serum only (ogliosecretory). Hypersensitivity to thalidomide, lenalidomide, pomalidomide, or dexamethasone Patients who received an allogeneic bone marrow or allogeneic peripheral blood stem cell transplant less than 12 months prior to initiation of study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Local Institution - 109
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85719
Country
United States
Facility Name
Colorado Blood Cancer Institute
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
University of Miami Medical Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136-2107
Country
United States
Facility Name
Local Institution - 108
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Local Institution - 103
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Local Institution - 104
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Local Institution - 105
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Local Institution - 101
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Gabrail Cancer Center Research
City
Canton
State/Province
Ohio
ZIP/Postal Code
44718
Country
United States
Facility Name
CTRC at The UT Health Science Center at San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Local Institution - 111
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Local Institution - 340
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Local Institution - 341
City
Nantes Cedex 01
ZIP/Postal Code
44093
Country
France
Facility Name
Local Institution - 330
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Local Institution - 320
City
Athens
ZIP/Postal Code
115 28
Country
Greece
Facility Name
Local Institution - 301
City
Pamplona
ZIP/Postal Code
31008
Country
Spain
Facility Name
Local Institution - 300
City
Salamanca
ZIP/Postal Code
37007
Country
Spain

12. IPD Sharing Statement

Links:
URL
https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
Description
BMS Clinical Trial Information
URL
https://www.bmsstudyconnect.com/s/US/English/USenHome
Description
BMS Clinical Trial Patient Recruiting

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Study of ACY-241 Alone and in Combination With Pomalidomide and Dexamethasone in Multiple Myeloma

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