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

Phase 1
Completed
Conditions
Myelodysplastic Syndrome
Interventions
Registration Number
NCT02018926
Lead Sponsor
Mirati Therapeutics Inc.
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
18
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Mocetinostat and azacitidineAzacitidineDrug: 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
Mocetinostat and azacitidineMocetinostatDrug: 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
Primary Outcome Measures
NameTimeMethod
Number of subjects with adverse events, including pericardial events, as a measure of safety6 months
Secondary Outcome Measures
NameTimeMethod
Number of subjects experiencing clinical disease response1 year

Trial Locations

Locations (9)

Georegetown University

🇺🇸

Washington, D.C., District of Columbia, United States

Lakes Research

🇺🇸

Miami Lakes, Florida, United States

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center

🇺🇸

Lebanon, New Hampshire, United States

New York Medical College

🇺🇸

Valhalla, New York, United States

Duke University Medical Center

🇺🇸

Durham, North Carolina, United States

St. Francis Hospital

🇺🇸

Greenville, South Carolina, United States

Cancer Care Centers of South Texas

🇺🇸

San Antonio, Texas, United States

Fletcher Allen Health Care and Vermont Cancer Center

🇺🇸

Burlington, Vermont, United States

Georegetown University
🇺🇸Washington, D.C., District of Columbia, United States

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