Phase 2 Study Adding Pracinostat to a Hypomethylating Agent (HMA) in Patients With MDS Who Failed to Respond to Single Agent HMA

Inclusion Criteria

• •1. Voluntary written informed consent
• •2. Histologically or cytologically documented diagnosis of MDS (any French-American-British classification \[FAB\] subtype)
• •3. Bone marrow blasts \>5% and \<30% and a peripheral white blood cell (WBC) count of \<20,000 /µL
• •4. Bone marrow biopsy, aspirates, and peripheral blood smears within 28 days of first study treatment
• •5. Group 1:
• •Primary failures: Progression after their most recent HMA therapy according to IWG criteria after receiving single agent azacitidine and/or single agent decitabine, or has worsening cytopenias (increased transfusion requirement), increased BM blasts, progression to a higher FAB type, or develops additional clinically significant cytogenetic abnormalities; Secondary failures: Relapse after any initial CR, PR, HI, or development of clinically significant cytogenetic abnormalities at any time according to IWG criteria after receiving single agent azacitidine or decitabine
• •Group 2:
• •Failure to achieve a response (any CR, PR or HI) according to IWG criteria definition of stable disease after the most recent HMA therapy (at least 6 cycles of azacitidine or 4 cycles of decitabine)
• •6. Must have demonstrated tolerability to single agent HMA
• •7. Able to start combination therapy within 3 months of the last single agent HMA dose with no other therapy for disease under study received during this interval
• •8. Not a candidate for hematopoietic stem cell transplant within 4 months of screening
• •9. ECOG performance status of 0, 1, or 2
• •10. Adequate organ function as evidenced by:
• •* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x the upper limit of normal (ULN)
• •* Total bilirubin ≤1.5 x ULN or total bilirubin of ≤2 mg/dL, whichever is higher
• •* Serum creatinine \<2 mg/dL, or creatinine clearance ≥60 mL/min
• •* QTcF interval ≤470 msec
• •11. Female or male patients ≥18 years-of-age
• •12. Male patients with female partners are required to use two forms of acceptable contraception; Female patients of childbearing potential must have a negative pregnancy test ≤7 days before first study treatment.
• •13. Willingness and ability to understand the nature of this trial and to comply