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

NCT02400242 | Terminated Phase 1

• 1 other identifier: ACE-MM-200
• Study Type: interventional
• Target: 85
• Locations: 5 countries
• Sites: 17

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).

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose of ACY-241 as monotherapy as assessed by dose limiting toxicities

  Cycle 1 (28 days)

• 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

  Cycle 2 (28 days)

Secondary Outcomes (12)

• Frequency and severity of AEs as measured by safety and tolerability

  Cycle 1 (28 days)

• Single- and multiple-dose peak-plasma concentration

  Cycle 1 days 1, 2, 15 and 16

• Single- and multiple-dose area under the plasma concentration versus time curve

  Cycle 1 days 1, 2, 15 and 16

• Change in acetylation of histone and tubulin as a measure of pharmacodynamics

  Cycles 1 days 1, 2, 15, 16 and 22

• Change in fetal hemoglobin expression as a measure of pharmacodynamics

  Cycles 1 days 1, 2, 15, 16 and 22

Study Arms (1)

ACY-241, Pomalidomide, and dexamethasone

EXPERIMENTAL

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).

Drug: ACY-241; Drug: Pomalidomide; Drug: Dexamethasone

Interventions

ACY-241 DRUG

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

Also known as: Histone deacetylase inhibitor

ACY-241, Pomalidomide, and dexamethasone

Pomalidomide DRUG

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

Also known as: immunomodulatory agent

ACY-241, Pomalidomide, and dexamethasone

Dexamethasone DRUG

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

Also known as: corticosteriod

ACY-241, Pomalidomide, and dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Celgene: lead

Study Sites (17)

Local Institution - 109

Tucson, Arizona, 85719, United States

Location

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

University of Miami Medical Center

Miami, Florida, 33136-2107, United States

Location

Local Institution - 108

Tampa, Florida, 33612, United States

Location

Local Institution - 103

Atlanta, Georgia, 30322, United States

Location

Local Institution - 104

Boston, Massachusetts, 02114, United States

Location

Local Institution - 105

Boston, Massachusetts, 02215, United States

Location

Local Institution - 101

New York, New York, 10065, United States

Location

Gabrail Cancer Center Research

Canton, Ohio, 44718, United States

Location

CTRC at The UT Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

Local Institution - 111

Seattle, Washington, 98104, United States

Location

Local Institution - 340

Lille, 59037, France

Location

Local Institution - 341

Nantes, 44093, France

Location

Local Institution - 330

Heidelberg, 69120, Germany

Location

Local Institution - 320

Athens, 115 28, Greece

Location

Local Institution - 301

Pamplona, 31008, Spain

Location

Local Institution - 300

Salamanca, 37007, Spain

Location

Related Links

• BMS Clinical Trial Information

MeSH Terms

Conditions

Multiple Myeloma

Interventions

citarinostat; Histone Deacetylase Inhibitors; pomalidomide; Adjuvants, Immunologic; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Immunologic Factors; Physiological Effects of Drugs; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2015
• First Posted: March 27, 2015
• Study Start: May 7, 2015
• Primary Completion: June 3, 2024
• Study Completion: June 3, 2024
• Last Updated: July 9, 2024

Record last verified: 2024-07

Locations

FR (2); ES (2); US (11); DE (1); GR (1)