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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01997840
Recruitment Status : Active, not recruiting
First Posted : November 28, 2013
Last Update Posted : May 24, 2019
Information provided by (Responsible Party):

Brief Summary:

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

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: ACY-1215 (Ricolinostat) in combination with pomalidomide and dexamethasone Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 101 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : March 1, 2014
Estimated Primary Completion Date : January 27, 2021
Estimated Study Completion Date : January 27, 2021

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
  • Ricolinostat
  • Dexamethasone

Primary Outcome Measures :
  1. 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 ]
  2. 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 ]

Secondary Outcome Measures :
  1. 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. ]
  2. 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. ]
  3. Phase 1b: Plasma levels of ACY-1215 and plasma levels of pomalidomide [ Time Frame: Up to 8 days post first dose ]
  4. 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 ]

Other Outcome Measures:
  1. Phase 2: Relationship between response to treatment and any cytogenetic abnormalities [ Time Frame: Duration on study, estimated average of 4 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01997840

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United States, Georgia
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States, 30322
United States, Indiana
Horizon Oncology Center
Lafayette, Indiana, United States, 47905
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Michigan
Univesity of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109-0922
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, New York
New York Medical College
Hawthorne, New York, United States, 10532
Mt. Sinai Medical Center Division of Hematology/Oncology
New York, New York, United States, 10029
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Ohio State University Arthur G. James Cancer Hospital
Columbus, Ohio, United States, 43210-1240
United States, Pennsylvania
University of Pittsburgh Medical Center - Cancer Pavilion
Pittsburgh, Pennsylvania, United States, 15232
United States, Texas
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1023
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Canada, Alberta
Tom Baker Cancer Center
Calgary, Alberta, Canada, T2N 4N2
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Ontario
Princess Margaret Cancer Centre
Toronto, Ontario, Canada, M5G 2M9
Alexandra Hospital, University of Athens
Athens, Greece, 11528
Azienda Ospedaliera Citta della Salute e della Scienza di Torino
Torino, Italy, 01012
Sponsors and Collaborators
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Principal Investigator: Noopur Raje, MD Massachusetts General Hospital

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Responsible Party: Celgene Identifier: NCT01997840     History of Changes
Other Study ID Numbers: ACE-MM-102
First Posted: November 28, 2013    Key Record Dates
Last Update Posted: May 24, 2019
Last Verified: May 2019
Keywords provided by Celgene:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Blood Protein Disorders
Hematologic Diseases
Dexamethasone acetate
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
BB 1101
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal