Omacetaxine and Decitabine in Acute Myelogenous Leukemia (AML) and Myelodysplastic Syndrome (MDS)

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a study
group based on when you join this study. Up to 2 groups of up to 6 participants (combined)
will be enrolled in the Phase 1 portion of the study, and up to 60 participants will be
enrolled in Phase 2.

If you are enrolled in Phase 1, the dose of decitabine you receive will depend on when you
joined this study. If the first group of participants to receive decitabine has intolerable
side effects, a second group will receive a lower dose.

If you are enrolled in Phase 2, you will receive decitabine at the highest dose that was
tolerated in Phase 1.

All participants will receive the same dose level of omacetaxine.

Study Drug Administration:

Each cycle is 28 days.

Omacetaxine will be given as an injection under your skin 2 times each day, 12 hours apart
(+/- 3 hours) on Days 1-3 of every cycle.

Decitabine will be given by vein over about 1 hour on Days 1-5 of every cycle.

Study Visits:

Every week (+/- 2 days), blood (about 2-3 teaspoons) will be collected for routine tests. If
the disease appears to get better, this blood will only be drawn every 2-4 weeks while you
are still receiving the study drugs, and every 4 to 8 weeks after that as long as you are on
study. If you live far from the clinic, this blood and urine can be collected at a clinic
close to your home, and the results will be reported to the study doctor.

At the beginning of every cycle, you will have a physical exam.

At Week 3 (+/- 7 days) and then every 4 weeks after that (+/- 7 days), you may (based on the
results of your blood tests) have a bone marrow aspirate/biopsy collected to check the status
of the disease and for cytogenetic testing.

Length of Study:

You may continue taking the study drugs for up to 3 years or as long as the doctor thinks it
is in your best interest. You will no longer be able to take the study drugs if the disease
gets worse, if intolerable side effects occur, or if you are unable to follow study
directions.

Your participation on the study will be over after the follow-up visits.

Follow Up:

You will have follow-up visits every 3-6 months for up to 5 years after you stop receiving
the study drugs. At these visits, you will have a physical exam. If you cannot come to the
clinic, you may just be called by the study staff and asked about your health. These calls
should last about 5-10 minutes.

This is an investigational study. Omacetaxine is FDA approved and commercially available for
the treatment of chronic myelogenous leukemia (CML). Its use in this study is
investigational. Decitabine is FDA approved and commercially available for the treatment of
MDS.

The study doctor can explain how the study drugs are designed to work.

Up to 66 participants will be enrolled in this study. All will take part at MD Anderson.

Inclusion Criteria:

1. Previously untreated AML (>/= 20% blasts) or AML M6. Patients with high-risk
(intermediate-2 or high by IPSS or >/= 10% blasts) MDS will also be eligible. Prior
therapy with hydroxyurea, biological or targeted therapy (e.g. flt3 inhibitors, other
kinase inhibitors, azacitidine), or hematopoietic growth factors is allowed. No prior
chemotherapy is allowed except for a single or a two day dose of cytarabine (up to 3
g/m2) for emergency use is also allowed as prior therapy.

2. Age >/= 70 years.

3. Eastern Cooperative Oncology Group (ECOG) performance status
4. Adequate hepatic (serum total bilirubin transaminase (SGPT) and/or SGOT mg/dL).

5. Patients must be willing and able to review, understand, and provide written consent
before starting therapy.

6. Men of childbearing potential who agree to use contraception prior to study entry and
for the duration of participation.

Exclusion Criteria:

1. New York Heart Association (NYHA) class III or IV heart disease, active ischemia or
any other uncontrolled cardiac condition such as angina pectoris, clinically
significant cardiac arrhythmia and requiring therapy, uncontrolled hypertension (blood
pressure >/= 160 systolic and >/= 110 diastolic not responsive to antihypertensive
medication), uncontrolled diabetes mellitus, or congestive heart failure.

2. Myocardial infarction in the previous 12 weeks (from the start of treatment).

3. Active and uncontrolled disease/infection as judged by the treating physician.

4. Acute promyelocytic leukemia (APL).