Omacetaxine + Azacitidine in Untreated Patients With High Grade MDS

This is an open-label, phase I/II study for previously untreated patients with high grade MDS
using omacetaxine and azacitidine. Phase I features dose escalation, where patients will be
assigned to one of three cohorts to receive different doses of omacetaxine with the standard
dose and schedule of azacitidine, over a 28 day cycle. Phase II features the maximum
tolerated dose from the Phase 1 study.

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
criteria22) or chronic myelomonocytic leukemia (CMML)-1 with greater than 5% bone
marrow blasts or CMML-2, also by WHO criteria22

2. Subject must have received no prior treatment with a hypomethylating agent for MDS

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

- bilirubin ≤ 3.0 × ULN, unless due to Gilbert's syndrome

8. 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.

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 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.