Phase 2 Study of Pracinostat With Azacitidine in Patients With Previously Untreated Myelodysplastic Syndrome

NCT ID: NCT01873703

Last Updated: 2018-09-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

102 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-06-30

Study Completion Date

2016-11-30

Brief Summary

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The purpose of this randomized, double-blind, placebo-controlled study is to determine the safety and efficacy of pracinostat compared to placebo when combined with azacitidine, and FDA approved treatment for Myelodysplastic Syndrome (MDS).

Detailed Description

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Conditions

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Myelodysplastic Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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pracinostat plus azacitadine

60 mg of pracinostat by mouth 3 times a week for 3 weeks followed by 1 week of rest repeated every 28 days.

75 mg/m2 Azacitidine for 7 days of each 28 day cycle, via subcutaneous (SC) injection or intravenous infusion if SC injections are intolerable

Group Type EXPERIMENTAL

pracinostat

Intervention Type DRUG

Histone deacetylase inhibitor (HDACi)

Azacitidine

Intervention Type DRUG

Active comparator 75 mg/m2 Azacitidine for 7 days of each 28 day cycle, via subcutaneous (SC) injection or intravenous infusion if SC injections are intolerable

Placebo with Azacitadine

Placebo by mouth 3 times a week for 3 weeks followed by 1 week of rest repeated every 28 days.

75 mg/m2 Azacitidine for 7 days of each 28 day cycle, via subcutaneous (SC) injection or intravenous infusion if SC injections are intolerable

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo

Azacitidine

Intervention Type DRUG

Active comparator 75 mg/m2 Azacitidine for 7 days of each 28 day cycle, via subcutaneous (SC) injection or intravenous infusion if SC injections are intolerable

Interventions

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pracinostat

Histone deacetylase inhibitor (HDACi)

Intervention Type DRUG

Placebo

Placebo

Intervention Type DRUG

Azacitidine

Active comparator 75 mg/m2 Azacitidine for 7 days of each 28 day cycle, via subcutaneous (SC) injection or intravenous infusion if SC injections are intolerable

Intervention Type DRUG

Other Intervention Names

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SB939 Vidaza

Eligibility Criteria

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Inclusion Criteria

* Voluntary written informed consent
* Histologically or cytologically documented diagnosis of MDS (any French-American-British \[FAB\] classification subtype; that is classified as intermediate 2 (1.5 to 2.0 points) or high risk (≥2.5 points) according to the International Prognostic Scoring System risk category, with \>5% and \<30% blasts, and a peripheral blast count of \<20,000
* Bone marrow aspirate smears and bone marrow biopsies within 28 days of first study treatment
* There must be a clinical indication for treatment with azacitidine.
* Previously untreated with hypomethylating agents (prior therapy with transfusions, hematopoietic growth factors, or immunosuppressive therapy is allowed)
* Eastern Cooperative Oncology Group performance status of 0, 1, or 2
* Adequate organ function as evidenced by:

1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x the upper limit of normal (ULN) (≤5 x ULN for patients with hepatic metastases
2. Total bilirubin ≤1.5 x ULN or total bilirubin of 2, whichever is higher
3. Serum creatinine \<2 mg/dL, or creatinine clearance ≤1.5 x ULN
4. QTcF interval ≤470 msec
* Female or male patients ≥18 years-of-age
* Male patients who are surgically sterile or willing to use adequate contraceptive measures or abstain from heterosexual intercourse during the entire study treatment period
* Female patients who are surgically sterile or post menopausal or female patients who are not of child-bearing potential and female patients of child-bearing potential who agree to use adequate contraceptive measures or abstain from intercourse during the study treatment period, who are not breastfeeding, and who have had a negative serum pregnancy test ≤7 days prior to first study treatment.
* Willingness and ability to comply with the trial and follow-up procedures

Exclusion Criteria

* Received any of the following within the specified time frame prior to administration of study medication:

1. Any investigational agent within 14 days or 5 half-lives prior to first study treatment, whichever is longer
2. Previous therapy for malignancy within 21 days prior to first study treatment, including any chemotherapy, immunotherapy, biological or hormonal therapy (6 weeks for nitrosoureas or mitomycin C)
3. Hydroxyurea within 48 hours prior to first study treatment
4. Hematopoietic growth factors: erythropoietin, granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor (GM-CSF), or thrombopoietin receptor agonists at least 7 days (14 days for Aranesp) prior to study enrollment
5. Major surgery within 4 weeks prior to first study treatment
* Patients that have not recovered from side effects of previous therapy
* Cardiopulmonary function exclusion:

1. Current unstable arrhythmia requiring treatment
2. History of symptomatic congestive heart failure (New York Heart Association Classes III or IV)
3. History of myocardial infarction within 6 months of enrollment
4. Current unstable angina
* Concomitant treatment with histone deacetylase (HDAC) inhibitors or drugs with significant action as HDAC inhibitors, such as valproic acid, is not permitted
* Clinical evidence of central nervous system involvement
* Patients with gastrointestinal (GI) tract disease, causing the inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis).
* Active infection with HIV or chronic hepatitis B or C
* Life-threatening illness unrelated to cancer, or any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with participation in this study
* Presence of a malignant disease within the last 12 months, with the exception of adequately treated in-situ carcinomas, basal or squamous cell carcinoma, or non-melanomatous skin cancer
* Inability (including psychological, familial, sociological, or geographical conditions) to comply with trial and/or follow-up procedures
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Helsinn Healthcare SA

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Guillermo Garcia-Manero, MD

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

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Southern Cancer Center

Mobile, Alabama, United States

Site Status

Scripps Cancer Center

La Jolla, California, United States

Site Status

Colorado Blood Cancer Institute

Denver, Colorado, United States

Site Status

Florida Cancer Specialists South

Fort Myers, Florida, United States

Site Status

Woodlands Medical Specialists

Pensacola, Florida, United States

Site Status

Florida Cancer Specialists North

St. Petersburg, Florida, United States

Site Status

Florida Cancer Specialist and Research Institute

Tallahassee, Florida, United States

Site Status

H. Lee Moffitt Cancer Center

Tampa, Florida, United States

Site Status

Fort Wayne Medical Oncology and Hematology

Fort Wayne, Indiana, United States

Site Status

Indiana University Simon Cancer Ctr

Indianapolis, Indiana, United States

Site Status

Sidney Kimmel Comprehensive Cancer at Johns Hopkins

Baltimore, Maryland, United States

Site Status

Center for Cancer and Blood Disorders

Bethesda, Maryland, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Michigan State University

Lansing, Michigan, United States

Site Status

Nebraska Methodist

Omaha, Nebraska, United States

Site Status

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Site Status

Weill Cornell Medical Center

New York, New York, United States

Site Status

Oncology Hematology Care

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

Tennessee Oncology - Chattanooga

Chattanooga, Tennessee, United States

Site Status

Sarah Cannon Cancer Center, Tennessee Oncology

Nashville, Tennessee, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Cancer Care Centers of South Texas

San Antonio, Texas, United States

Site Status

Swedish Cancer Institute

Seattle, Washington, United States

Site Status

Countries

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United States

Related Links

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http://MEIPharma.com

Sponsor website

Other Identifiers

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MEI-003

Identifier Type: -

Identifier Source: org_study_id

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