Safety Study of Mocetinostat in Combination With Azacitidine in Subjects With MDS

A Phase I/II, Multi-Center Study of Mocetinostat (MGCD0103) in Combination With Azacitidine in Subjects With Intermediate or High Risk Myelodysplastic Syndrome (MDS)

Mocetinostat is an orally administered histone deacetylase (HDAC) inhibitor. Azacitidine is a hypomethylating agent (HMA) used to treat MDS. In this study, patients with intermediate- or high-risk MDS will receive treatment with mocetinostat and azacitidine to evaluate the safety of the study treatment. Safety assessments will include echocardiograms, electrocardiograms and routine safety laboratory studies (hematology and serum chemistry). In addition, clinical response to treatment will be monitored using bone marrow aspirates or biopsies, and other routine methods.

Study Overview

• Status: Completed
• Conditions: Myelodysplastic Syndrome
• Intervention / Treatment: Drug: Mocetinostat; Drug: Azacitidine

Detailed Description

The study will include multiple cohorts of patients. In the first cohort, patients may have previously received treatment with hypomethylating agents such as azacitidine. In later cohorts, prior treatment with this class of anti-cancer agents will be excluded. Later cohorts will include patients that are receiving this class of agents, specifically azacitidine, for the first time.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, D.C., District of Columbia, United States, 20057
      • Georegetown University
  • Florida
    • Miami Lakes, Florida, United States, 33014
      • Lakes Research
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center
  • New York
    • Valhalla, New York, United States, 10595
      • New York Medical College
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center
  • South Carolina
    • Greenville, South Carolina, United States, 29601
      • St. Francis Hospital
  • Texas
    • New Braunfels, Texas, United States, 78130
      • Cancer Care Centers of South Texas
    • San Antonio, Texas, United States, 78229
      • Cancer Care Centers of South Texas
  • Vermont
    • Burlington, Vermont, United States, 05405
      • Fletcher Allen Health Care and Vermont Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Diagnosis of intermediate- or high-risk (IPSS criteria) myelodysplastic syndrome.

Cohort 1: Any prior treatment, enrollment complete. Cohort 2: Limited or no prior treatment for MDS. Prior treatment should not include hypomethylating agents such as azacitidine or decitabine, or HDAC inhibitors.

ECOG Performance Status 0 or 1.

Exclusion Criteria:

Current or history of small, moderate or large pericardial effusion, tamponade and/or pericarditis.

Significant cardiac abnormalities such as recent myocardial infarction, congestive heart failure ≥ Class 3, or symptomatic, uncontrolled atrial fibrillation, atrial flutter or sinus tachycardia.

Prolonged QT/QTc interval.

Other active cancer excluding basal cell carcinoma or cervical intraepithelial neoplasia.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Mocetinostat and azacitidine; Drug: Mocetinostat (MGCD0103) Mocetinostat (a histone deacetylase [HDAC] inhibitor) 70 mg or 90 mg dose, oral capsules 3 times weekly beginning on day 5 for 10 doses in each 28 day cycle Drug: Azacitidine (Vidaza) Azacitidine (a hypomethylating agent [HMA]) 75 mg/m2 dose, by intravenous (IV) infusion or subcutaneous (SC) injection beginning on day 1 for 7 doses in each 28 day cycle

Drug: Mocetinostat; Mocetinostat (a histone deacetylase [HDAC] inhibitor) 70 mg or 90 mg dose, oral capsules 3 times weekly beginning on day 5, for 10 doses in each 28 day cycle; Other Names: MGCD0103; Drug: Azacitidine; Azacitidine (a hypomethylating agent [HMA]) 75 mg/m2 dose, by intravenous (IV) infusion or subcutaneous (SC) injection beginning on day 1 for 7 doses in each 28 day cycle; Other Names: Vidaza

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of subjects with adverse events, including pericardial events, as a measure of safety	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of subjects experiencing clinical disease response	1 year

Collaborators and Investigators

• Sponsor: Mirati Therapeutics Inc.
• Investigators: Study Director: Isan Chen, MD, Mirati Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: December 12, 2013
• First Submitted That Met QC Criteria: December 17, 2013
• First Posted (Estimate): December 23, 2013

Study Record Updates

• Last Update Posted (Actual): September 14, 2017
• Last Update Submitted That Met QC Criteria: September 6, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: MDS; Azacitidine; Myelodysplastic syndrome; HDAC; Vidaza; HMA; Mocetinostat
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Histone Deacetylase Inhibitors; Azacitidine; Mocetinostat
• Other Study ID Numbers: 0103-014