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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Myelodysplastic Syndrome

Intervention / Treatment
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* Drug: Mocetinostat
* Drug: Azacitidine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mocetinostat and azacitidine<br>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<br>* 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<br>* Other names: MGCD0103;Drug: Azacitidine<br>* 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<br>* Other names: Vidaza;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mocetinostat, Azacitidine, Vidaza, Myelodysplastic syndrome, HDAC, HMA, MDS