Omacetaxine and Azacitidine in Treating Participants with High Grade Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia

Inclusion Criteria

• Subject must have confirmation of high grade myelodysplastic syndromes (MDS) (MDS with excess blasts by World Health Organization [WHO] criteria) or chronic myelomonocytic leukemia with greater than 5% bone marrow blasts
• 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 a hypomethylating (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
• Subject must have a projected life expectancy of at least 12 weeks
• Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
• 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
• Aspartate aminotransferase (AST) =< 3.0 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) =< 3.0 x ULN
• Direct bilirubin =< 3.0 x ULN
• Non-sterile male subjects must use contraceptive methods with partner(s) from time of enrollment and continuing up to 90 days 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
• 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
• 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

Exclusion Criteria

• Subject is known to be positive for human immunodeficiency virus (HIV). HIV testing is not required
• Subject is known to be positive for hepatitis B or C infection with the exception of those with an undetectable viral load. Hepatitis B or C testing is not required and subjects with serologic evidence of prior vaccination to hepatitis B virus (HBV) (i.e., hepatitis B surface antigen [HBs Ag], anti-hepatitis B surface antibody [HBs]+ and anti-hepatitis B core antigen [HBc]–) may participate
• Subject has any history of clinically significant condition(s) that in the opinion of the investigator would adversely affect his/her participating in this study including, but not limited to: * New York Heart Association heart failure > class 2 * Renal, neurologic, psychiatric, endocrine, metabolic, immunologic, hepatic, cardiovascular disease, or bleeding disorder independent of leukemia
• Subject exhibits evidence of uncontrolled systemic infection requiring therapy (viral, bacterial or fungal). Patients on antibiotics with controlled systemic symptoms will not be excluded
• Subject has uncontrolled diabetes
• Subject has had a recent major hemorrhage or has a bleeding diathesis associated with a high risk of bleeding
• Pregnant and breastfeeding females
• Subject has a history of other malignancies prior to study entry, except for: * Adequately treated in situ carcinoma of the breast or cervix uteri * Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin * Prostate cancer with no plans for therapy of any kind * Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent