ACY-1215 (Ricolinostat) in Combination With Pomalidomide and Low-dose Dex in Relapsed-and-Refractory Multiple Myeloma

February 14, 2024 updated by: Celgene

A Phase 1B/2 Multi-Center, Open Label, Dose-Escalation Study to Determine the Maximum Tolerated Dose, Safety, and Efficacy of ACY-1215 (RICOLINOSTAT) in Combination With Pomalidomide and Low-Dose Dexamethasone in Patients With Relapsed and Refractory Multiple Myeloma

Phase 1b: To evaluate the side effects and determine the best dose of ACY-1215 in combination with Pomalidomide and low-dose dexamethasone in patients with relapsed-and-refractory multiple myeloma.

Phase 2: To determine the overall response rate of ACY-1215 in combination with Pomolidomide and low-dose dexamethasone in patients with relapsed-and-refractory multiple myeloma

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

103

Phase

  • Phase 2
  • 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

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Local Institution - 201
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic

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

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Must have a documented diagnosis of multiple myeloma and have relapsed-and-refractory disease. Patients must have received at least 2 lines of prior therapies. Patients must have relapsed after having achieved at least stable disease (SD) for at least one cycle of treatment to at least one prior regimen and then developed progressive disease (PD). Patients must also have documented evidence of PD during or within 60 days (measured from the end of the last cycle) of completing treatment with the last anti-myeloma drug regimen used just prior to study entry (refractory disease)
  • Must have undergone prior treatment with at least 2 cycles of lenalidomide and at least 2 cycles of a proteasome inhibitor (either in separate regimens or within the same regimen)
  • Must not be a candidate for autologous stem cell transplant (ASCT), has declined the option of ASCT, or has relapsed after prior ASCT
  • Must have measurable levels of myeloma paraprotein in serum (≥ 0.5 g/dL) or urine (≥ 0.2 g/24 hours)
  • Must have Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
  • Females of child bearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to, and again within 24 hours of starting pomalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking pomalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods,and Education and Counseling Guidance must be followed per protocol
  • Must be able to take acetylsalicylic acid (ASA) (81 or 325 mg) daily as prophylactic anticoagulation. Patients intolerant to ASA may use low molecular weight heparin. Lovenox is recommended. Coumadin will be allowed provided the patient is fully anticoagulated, with an international normalized ratio (INR) of 2 to 3

Exclusion Criteria:

  • Pregnant or lactating females
  • Prior therapy with HDAC inhibitor

  • Any of the following laboratory abnormalities:

    • ANC < 1,000/µL
    • Platelet count < 75,000/ µL for patients in whom < 50% of bone marrow nucleated cells are plasma cells; and < 50,000/ µL for patients in whom ≥ 50% of bone marrow nucleated cells are plasma cells
    • Hemoglobin < 8g/dL (<4.9 mmol/L; prior red blood cell [RBC] transfusion is permitted)
    • Creatine clearance < 45mL/min according to Cockcroft-Gault formula. If creatine clearance calculated from the 24-hour urine sample is ≥ 45 mL/min, patient will qualify for the study
    • Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST), or serum glutamic pyruvic transaminase (SGPT)/ alanine aminotransferase (ALT) > 3.0 × ULN
    • Serum total bilirubin > 2.0 mg/dL

  • Prior history of malignancies, other than MM, unless the patient has been free of the disease for ≥ 3 years. Exceptions include the following:

    • Basal or squamous cell carcinoma of the skin
    • Carcinoma in situ of the cervix or breast
    • Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b)
  • Corrected QT interval using Fridericia's formula (QTcF) value > 480 msec at screening; family or personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy; previous history of drug-induced QTc prolongation or the need for treatment with medications known or suspected of producing prolonged QTc intervals on electrocardiogram (ECG)
  • Positive human immunodeficiency virus (HIV), hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection
  • Hypersensitivity to thalidomide, lenalidomide, or dexamethasone (such as Steven Johnson Syndrome). Hypersensitivity, such as rash, that can be medically managed is allowable
  • Peripheral neuropathy ≥ Grade 2 despite supportive therapy
  • Radiotherapy or systemic therapy (standard or an investigational or biologic anticancer agent) within 14 days of initiation of study drug treatment
  • Current enrollment in another clinical trial involving treatment and/or is receiving an investigational agent for any reason
  • Inability or unwillingness to comply with birth control requirements or regional REMS/RevAid programs

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
Intervention / Treatment
Experimental: ACY-1215 in combination with pomalidomide and dexamethasone
ACY-1215 (Ricolinostat) in combination with pomalidomide and dexamethasone
Drug: ACY-1215 (Ricolinostat) in combination with pomalidomide and dexamethasone
ACY-1215 (Ricolinostat) 160mg QD Days 1-21 with pomalidomide 4mg QD Days 1-21 and dexamethasone 40mg QD Days 1,8,15,22 of a 28-day cycle
Other Names:
  • Pomalyst
  • Dexamethasone
  • Ricolinostat

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Phase 1b: MTD and dosing schedule of ACY-1215 administered in combination with pomalidomide and low-dose dexamethasone in patients with MM
Time Frame: 28 days
28 days
Phase 2: Overall response rate of ACY-1215 in combination with pomalidomide and dexamethasone in patients with relapsed-and-refractory multiple myeloma
Time Frame: Every 56 days for the duration on treatment, an estimated average of 4 months
Every 56 days for the duration on treatment, an estimated average of 4 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Phase 1b & 2: Safety assessed by type, frequency and severity of AEs and relationship of AEs to study drug
Time Frame: Upon completion of a 28 day treatment cycle and for the duration of treatment, an estimated average of 4 months.
Upon completion of a 28 day treatment cycle and for the duration of treatment, an estimated average of 4 months.
Phase 1b and 2: Efficacy assessed by time to response, duration of response, time to progression, progression free survival, and objective response as assessed by a central adjudication committee
Time Frame: Every 56 days on treatment, estimated average of 4 months. Survival will be evaluated every 4 months for up to 5 years.
Every 56 days on treatment, estimated average of 4 months. Survival will be evaluated every 4 months for up to 5 years.
Phase 1b: Plasma levels of ACY-1215 and plasma levels of pomalidomide
Time Frame: Up to 8 days post first dose
Up to 8 days post first dose
Phase 1b: Exposure response of treatment including biomarkers relating to intracellular protein acetylation, protein levels, mRNA and microRA expression profiles.
Time Frame: Up to 24 hours post first dose
Up to 24 hours post first dose

Other Outcome Measures

Outcome Measure
Time Frame
Phase 2: Relationship between response to treatment and any cytogenetic abnormalities
Time Frame: Duration on study, estimated average of 4 months
Duration on study, estimated average of 4 months

Collaborators and Investigators

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

Sponsor

Celgene

Investigators

  • 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)

March 1, 2014

Primary Completion (Estimated)

February 29, 2024

Study Completion (Estimated)

February 29, 2024

Study Registration Dates

First Submitted

November 20, 2013

First Submitted That Met QC Criteria

November 25, 2013

First Posted (Estimated)

November 28, 2013

Study Record Updates

Last Update Posted (Actual)

February 15, 2024

Last Update Submitted That Met QC Criteria

February 14, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACE-MM-102

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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