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

July 8, 2024 updated by: Celgene

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

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
85

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Lille, France, 59037
        • Local Institution - 340
      • Nantes Cedex 01, France, 44093
        • Local Institution - 341
  • Germany
      • Heidelberg, Germany, 69120
        • Local Institution - 330
  • Greece
      • Athens, Greece, 115 28
        • Local Institution - 320
  • Spain
      • Pamplona, Spain, 31008
        • Local Institution - 301
      • Salamanca, Spain, 37007
        • Local Institution - 300
  • United States
    • Arizona
      • Tucson, Arizona, United States, 85719
        • Local Institution - 109
    • Colorado
      • Denver, Colorado, United States, 80218
        • Colorado Blood Cancer Institute
    • Florida
      • Miami, Florida, United States, 33136-2107
        • University of Miami Medical Center
      • Tampa, Florida, United States, 33612
        • Local Institution - 108
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Local Institution - 103
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Local Institution - 104
      • Boston, Massachusetts, United States, 02215
        • Local Institution - 105
    • New York
      • New York, New York, United States, 10065
        • Local Institution - 101
    • Ohio
      • Canton, Ohio, United States, 44718
        • Gabrail Cancer Center Research
    • Texas
      • San Antonio, Texas, United States, 78229
        • CTRC at the UT Health Science Center at San Antonio
    • Washington
      • Seattle, Washington, United States, 98104
        • Local Institution - 111

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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).
Drug: ACY-241
Dose escalation up to 480 mg administered orally on Days 1-21 of a 28 day cycle.
Other Names:
  • Histone deacetylase inhibitor
Drug: Pomalidomide
4 mg qd dosed on days 1-21 of a 28 day cycle
Other Names:
  • immunomodulatory agent
Drug: Dexamethasone
40 mg qd on days 1, 8, 15, 22
Other Names:
  • corticosteriod

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Maximum tolerated dose of ACY-241 as monotherapy as assessed by dose limiting toxicities
Time Frame: Cycle 1 (28 days)
Cycle 1 (28 days)
Maximum tolerated dose of ACY-241 in combination with pomalidomide and low dose dexamethasone as assessed by dose limiting toxicities
Time Frame: Cycle 2 (28 days)
First cycle of combination therapy
Cycle 2 (28 days)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Frequency and severity of AEs as measured by safety and tolerability
Time Frame: Cycle 1 (28 days)
Cycle 1 (28 days)
Single- and multiple-dose peak-plasma concentration
Time Frame: Cycle 1 days 1, 2, 15 and 16
Cycle 1 days 1, 2, 15 and 16
Single- and multiple-dose area under the plasma concentration versus time curve
Time Frame: Cycle 1 days 1, 2, 15 and 16
Cycle 1 days 1, 2, 15 and 16
Change in acetylation of histone and tubulin as a measure of pharmacodynamics
Time Frame: Cycles 1 days 1, 2, 15, 16 and 22
Cycles 1 days 1, 2, 15, 16 and 22
Change in fetal hemoglobin expression as a measure of pharmacodynamics
Time Frame: Cycles 1 days 1, 2, 15, 16 and 22
Cycles 1 days 1, 2, 15, 16 and 22
ACY-241 metabolite concentration in blood samples
Time Frame: Cycles 1 days 1, 2, 15, 16 and 22
Cycles 1 days 1, 2, 15, 16 and 22
Exposure response analyses of potential biomarkers of response.
Time Frame: Cycles 1 days 1, 2, 15, 16 and 22
Cycles 1 days 1, 2, 15, 16 and 22
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
Beginning at Cycle 2 (28 day cycle each) until end of treatment
Change in fetal hemoglobin expression as a measure of pharmacodynamics
Time Frame: Cycle 2 days 1, 2, 15, 16 and 22
Cycle 2 days 1, 2, 15, 16 and 22
Change in acetylation of histone and tubulin as a measure of pharmacodynamics
Time Frame: Cycle 2 days 1, 2, 15, 16 and 22
Cycle 2 days 1, 2, 15, 16 and 22
Single- and multiple-dose area under the plasma concentration versus time curve
Time Frame: Cycle 2 days 1, 2, 15, and 16
Cycle 2 days 1, 2, 15, and 16
Quantification of M-protein as a measure of anti-tumor activity
Time Frame: Day 1 of each cycle beginning at Cycle 2
Day 1 of each cycle beginning at Cycle 2

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Celgene

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 7, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 3, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 3, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 3, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 23, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 27, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 9, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 8, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ACE-MM-200

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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