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

NCT01873703 | Completed Phase 2 DMC

• 1 other identifier: MEI-003
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 24

Brief Summary

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).

Conditions

Myelodysplastic Syndrome

Keywords

MDS; High risk myelodysplastic syndrome; Intermediate-2 Myelodysplastic syndrome; Untreated

Outcome Measures

Primary Outcomes (1)

• Estimate efficacy

  Estimate the relative efficacy, measured by complete remission rate of treatment wiht pracinostat plus azacitidine versus placebo plus azacitidine

  6 months

Secondary Outcomes (7)

• Overall response rate

  6 months

• Hematologic Improvement

  6 months

• Duration of response

  6 months

• Progression free survival

  12 months

• Rate of leukemic transformation

  6 - 24 months

Study Arms (2)

pracinostat plus azacitadine

EXPERIMENTAL

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

Drug: pracinostat; Drug: Azacitidine

Placebo with Azacitadine

PLACEBO COMPARATOR

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

Drug: Placebo; Drug: Azacitidine

Interventions

pracinostat DRUG

Histone deacetylase inhibitor (HDACi)

Also known as: SB939

pracinostat plus azacitadine

Placebo DRUG

Placebo

Placebo with Azacitadine

Azacitidine 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

Also known as: Vidaza

Placebo with Azacitadine; pracinostat plus azacitadine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x the upper limit of normal (ULN) (≤5 x ULN for patients with hepatic metastases
• Total bilirubin ≤1.5 x ULN or total bilirubin of 2, whichever is higher
• Serum creatinine \<2 mg/dL, or creatinine clearance ≤1.5 x ULN
• 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

You may not qualify if:

• Received any of the following within the specified time frame prior to administration of study medication:
• Any investigational agent within 14 days or 5 half-lives prior to first study treatment, whichever is longer
• 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)
• Hydroxyurea within 48 hours prior to first study treatment
• 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
• Major surgery within 4 weeks prior to first study treatment
• Patients that have not recovered from side effects of previous therapy
• Current unstable arrhythmia requiring treatment
• History of symptomatic congestive heart failure (New York Heart Association Classes III or IV)
• History of myocardial infarction within 6 months of enrollment
• 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

Sponsors & Collaborators

• Helsinn Healthcare SA: lead

Study Sites (24)

Southern Cancer Center

Mobile, Alabama, 36608, United States

Location

Scripps Cancer Center

La Jolla, California, 92037, United States

Location

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Florida Cancer Specialists South

Fort Myers, Florida, 33916, United States

Location

Woodlands Medical Specialists

Pensacola, Florida, 32503, United States

Location

Florida Cancer Specialists North

St. Petersburg, Florida, 33705, United States

Location

Florida Cancer Specialist and Research Institute

Tallahassee, Florida, 32308, United States

Location

H. Lee Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Fort Wayne Medical Oncology and Hematology

Fort Wayne, Indiana, 46804, United States

Location

Indiana University Simon Cancer Ctr

Indianapolis, Indiana, 46202, United States

Location

Sidney Kimmel Comprehensive Cancer at Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

Center for Cancer and Blood Disorders

Bethesda, Maryland, 20817, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Michigan State University

Lansing, Michigan, 48910, United States

Location

Nebraska Methodist

Omaha, Nebraska, 68114, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89148, United States

Location

Weill Cornell Medical Center

New York, New York, 10065, United States

Location

Oncology Hematology Care

Cincinnati, Ohio, 45242, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Tennessee Oncology - Chattanooga

Chattanooga, Tennessee, 37404, United States

Location

Sarah Cannon Cancer Center, Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Cancer Care Centers of South Texas

San Antonio, Texas, 78229, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

Related Links

• Sponsor website

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

SB939 compound; Azacitidine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Guillermo Garcia-Manero, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2013
• First Posted: June 10, 2013
• Study Start: June 1, 2013
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2016
• Last Updated: September 13, 2018

Record last verified: 2018-09

Locations

US (24)