Omacetaxine + Azacitidine in Untreated Patients With High Grade MDS

Inclusion Criteria

• •A subject will be eligible for study participation if he/she meets the following criteria within 14 days prior to the first day of therapy (bone marrow biopsy can be performed 28 days prior to the first day of therapy).
• •1. Subject must have confirmation of high grade MDS (MDS with excess blasts by WHO criteria) or chronic myelomonocytic leukemia with greater than 5% bone marrow blasts
• •2. Subjects in the newly-diagnosed Phase 2 cohort must have received no prior treatment with a hypomethylating agent for MDS. Subjects in the relapsed/refractory Phase 2 cohort must have received at least 1 prior line of an HMA-containing regimen. "Refractory" is defined as having received at least four cycles of any HMA or HMA-containing regimen with \>5-19% bone marrow blasts. "Relapsed" is defined as having \>5-19% bone marrow blasts after having achieved a morphologic remission (≤5% bone marrow blasts) after at least one cycle of any HMA or HMA-containing regimen.
• •3. Subject must be ≥ 18 years of age
• •4. Subject must have a projected life expectancy of at least 12 weeks
• •5. Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance status of ≤2
• •6. Subject must have adequate renal function as demonstrated by a calculated creatinine clearance ≥ 30 mL/min; determined via urine collection for 24-hour creatinine clearance or by the Cockcroft Gault formula
• •7. Subject must have adequate liver function as demonstrated by:
• •* aspartate aminotransferase (AST) ≤ 3.0 × ULN
• •* alanine aminotransferase (ALT) ≤ 3.0 × ULN
• •* direct bilirubin ≤ 3.0 × ULN
• •8. Non-sterile male subjects must use contraceptive methods with partner(s) from time of enrollment and continuing up to 90 das after the last dose of study drug. Male subjects must agree to refrain from sperm donation from initial study drug administration until 90 days after the last dose of study drug.
• •9. Female subjects must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) for at least 28 days before starting omacetaxine; 2) throughout the entire duration of omacetaxine treatment; 3) during dose interruptions; and 4) for at least 90 days after omacetaxine discontinuation.
• •10. Subject must voluntarily sign and date an informed consent, approved by an Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.