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

Sponsor

Mirati Therapeutics Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT02018926

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

1.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndrome	Drug: Mocetinostat Drug: Azacitidine	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Dec 1, 2013

Actual Primary Completion Date :

Sep 1, 2015

Actual Study Completion Date :

Sep 1, 2015

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Number of subjects with adverse events, including pericardial events, as a measure of safety [6 months]

Secondary Outcome Measures

Number of subjects experiencing clinical disease response [1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Georegetown University	Washington, D.C.	District of Columbia	United States	20057
2	Lakes Research	Miami Lakes	Florida	United States	33014
3	Mayo Clinic	Rochester	Minnesota	United States	55905
4	Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
5	New York Medical College	Valhalla	New York	United States	10595
6	Duke University Medical Center	Durham	North Carolina	United States	27705
7	St. Francis Hospital	Greenville	South Carolina	United States	29601
8	Cancer Care Centers of South Texas	New Braunfels	Texas	United States	78130
9	Cancer Care Centers of South Texas	San Antonio	Texas	United States	78229
10	Fletcher Allen Health Care and Vermont Cancer Center	Burlington	Vermont	United States	05405