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

NCT ID: NCT02400242

Last Updated: 2024-07-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 85 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-07
• Study Completion Date: 2024-06-03

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.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ACY-241, Pomalidomide, and dexamethasone

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).

Group Type: EXPERIMENTAL

ACY-241

Intervention Type: DRUG

Dose escalation up to 480 mg administered orally on Days 1-21 of a 28 day cycle.

Pomalidomide

Intervention Type: DRUG

4 mg qd dosed on days 1-21 of a 28 day cycle

Dexamethasone

Intervention Type: DRUG

40 mg qd on days 1, 8, 15, 22

Interventions

ACY-241

Dose escalation up to 480 mg administered orally on Days 1-21 of a 28 day cycle.

Intervention Type: DRUG

Pomalidomide

4 mg qd dosed on days 1-21 of a 28 day cycle

Intervention Type: DRUG

Dexamethasone

40 mg qd on days 1, 8, 15, 22

Intervention Type: DRUG

Other Intervention Names

Histone deacetylase inhibitor; immunomodulatory agent; corticosteriod

Eligibility Criteria

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.

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

Local Institution - 109

Tucson, Arizona, United States

Colorado Blood Cancer Institute

Denver, Colorado, United States

University of Miami Medical Center

Miami, Florida, United States

Local Institution - 108

Tampa, Florida, United States

Local Institution - 103

Atlanta, Georgia, United States

Local Institution - 104

Boston, Massachusetts, United States

Local Institution - 105

Boston, Massachusetts, United States

Local Institution - 101

New York, New York, United States

Gabrail Cancer Center Research

Canton, Ohio, United States

CTRC at The UT Health Science Center at San Antonio

San Antonio, Texas, United States

Local Institution - 111

Seattle, Washington, United States

Local Institution - 340

Lille, , France

Local Institution - 341

Nantes, , France

Local Institution - 330

Heidelberg, , Germany

Local Institution - 320

Athens, , Greece

Local Institution - 301

Pamplona, , Spain

Local Institution - 300

Salamanca, , Spain

Countries

United States; France; Germany; Greece; Spain

Related Links

https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html

BMS Clinical Trial Information

Other Identifiers

ACE-MM-200

Identifier Type: -

Identifier Source: org_study_id