The following criteria is provided for health care professionals.

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.

Exclusion Criteria:

A subject will not be eligible for study participation if he/she meets any of the following criteria:

1. Subject is known to be positive for HIV. HIV testing is not required.
2. 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 HBV (i.e., HBs Ag, anti-HBs+ and anti-HBc-) may participate.
3. 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
4. Subject exhibits evidence of uncontrolled systemic infection requiring therapy (viral, bacterial or fungal). Patients on antibiotics with controlled systemic symptoms will not be excluded.
5. Subject has uncontrolled diabetes
6. Subject has had a recent major hemorrhage or has a bleeding diathesis associated with a high risk of bleeding
7. Pregnant and breastfeeding females.
8. 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.