Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 4 for:    Ricolinostat | Myeloma
Previous Study | Return to List | Next Study

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.
 
ClinicalTrials.gov Identifier: NCT01997840
Recruitment Status : Active, not recruiting
First Posted : November 28, 2013
Last Update Posted : August 31, 2020
Sponsor:
Information provided by (Responsible Party):
Celgene

Tracking Information
First Submitted Date  ICMJE November 20, 2013
First Posted Date  ICMJE November 28, 2013
Last Update Posted Date August 31, 2020
Actual Study Start Date  ICMJE March 1, 2014
Estimated Primary Completion Date June 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 25, 2013)
  • 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 ]
  • 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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 17, 2016)
  • 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. ]
  • 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. ]
  • Phase 1b: Plasma levels of ACY-1215 and plasma levels of pomalidomide [ Time Frame: 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 25, 2013)
  • 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. ]
  • 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. ]
  • Phase 1b: Plasma levels of ACY-1215 and plasma levels of pomalidomide [ Time Frame: Up to 8 days post first dose ]
  • Phase 1b: Exposure response of treatment including biomarkers relatating to intracellular protein acetylation, protein levels, mRNA and microRA expression profiles. [ Time Frame: Up to 24 hours post first dose ]
Current Other Pre-specified Outcome Measures
 (submitted: November 25, 2013)
Phase 2: Relationship between response to treatment and any cytogenetic abnormalities [ Time Frame: Duration on study, estimated average of 4 months ]
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE ACY-1215 (Ricolinostat) in Combination With Pomalidomide and Low-dose Dex in Relapsed-and-Refractory Multiple Myeloma
Official Title  ICMJE 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
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

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE 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
Study Arms  ICMJE Experimental: ACY-1215 in combination with pomalidomide and dexamethasone
ACY-1215 (Ricolinostat) in combination with pomalidomide and dexamethasone
Intervention: Drug: ACY-1215 (Ricolinostat) in combination with pomalidomide and dexamethasone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: October 23, 2017)
101
Original Estimated Enrollment  ICMJE
 (submitted: November 25, 2013)
100
Estimated Study Completion Date  ICMJE June 30, 2022
Estimated Primary Completion Date June 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Greece,   Italy,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01997840
Other Study ID Numbers  ICMJE ACE-MM-102
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Celgene
Study Sponsor  ICMJE Celgene
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Noopur Raje, MD Massachusetts General Hospital
PRS Account Celgene
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP