A Phase II Randomized, Double-Blinded, Placebo-Controlled Study of Pracinostat in Combination with Azacitidine in Patients with Previously Untreated International Prognostic Scoring System (IPSS) Intermediate Risk 2 or High-Risk Myelodysplastic Syndrome (MDS) (Protocol MDS 14/MEI-003

Trial ID:
IRB-13-6230
Marin Xavier
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).

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