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

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:

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

Exclusion Criteria:

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

Cardiopulmonary function exclusion:

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
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