The goal of this clinical research study is to learn if omacetaxine given with cytarabine can help to control the disease in patients with AML or high-risk MDS. The safety of the study drugs will also be studied.

Study Drugs:

Omacetaxine is designed to block certain proteins, which may cause cancer cells to die.

Cytarabine is designed to insert itself into DNA (the genetic material of cells) of cancer cells and stop the DNA from repairing itself.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive omacetaxine and cytarabine as an injection under the skin. You will receive instructions on how to give these injections to yourself. You will be given a Research Medication Diary to record the drugs you take each day. You must bring the Research Medication Diary and any unused drugs with you to each study visit. You will also be told how to properly store the drugs.

On Days 1-3 of each cycle, you will give yourself an injection of omacetaxine every 12 hours (+/- 3 hours).

On Days 1-7 of each cycle, you will give yourself an injection of cytarabine every 12 hours (+/- 3 hours).

Each cycle will be 4-7 weeks, depending on how well the disease responds to the study drugs.

Depending on how the disease responds to the study drugs, the number of days you receive your injections may stay the same, increase, or decrease. Your doctor will discuss this with you.

Study Visits:

On Day 1 of each cycle, you will have a physical exam.

Women who are able to become pregnant must have a negative blood (about 1/2 teaspoon) or urine pregnancy test within 3 days before receiving the first dose of study drug.

Blood (about 1 tablespoon) will be drawn every week for routine tests. Once you have a response to treatment, blood will then be drawn every 2-4 weeks while you are receiving treatment. If your doctor thinks it is needed, you may have more blood samples drawn during Cycles 1 and 2.

On Day 21 of Cycle 1 (+/- 7 days), then every 4 weeks after that, you will have a bone marrow aspiration and/or biopsy to check the status of the disease. If the doctor thinks it is needed, these may be done more or less often, depending on your response to treatment.

Length of Study:

You may receive up to 24 cycles of treatment. You will be taken off study early if the disease gets worse or intolerable side effects occur.

Follow-up:

Once you stop taking the study drugs, you will have follow-up for 5 years.

Every 4-8 weeks, blood (about 1 tablespoon) will be drawn for routine tests. If you cannot return to the clinic, you may have blood drawn at a clinic close to your home.

Every 3-6 months, you will be contacted during a clinic visit and asked how you are doing. If you cannot make it to the clinic for this visit, you will be called. The phone call should last about 5 minutes.

This is an investigational study. Omacetaxine is FDA approved to treat patients with certain types of leukemia. Its use in this study is investigational. Cytarabine is FDA approved and commercially available for the treatment of AML. The use of these drugs in combination is investigational.

Up to 60 patients will take part in this study. All will be enrolled at M. D. Anderson.

Inclusion Criteria:

1. Previously untreated AML (>/= 20% blasts). Patients with high-risk (intermediate-2 or high by International Prostate Symptom Score (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. 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 >/= 60 years.
3. Eastern Cooperative Oncology Group (ECOG) performance status </= 2.
4. Adequate hepatic (serum total bilirubin </= 1.5 x ULN, serum glutamate pyruvate transaminase (SGPT) and/or serum glutamate oxaloacetate transaminase (SGOT) </= 2.5 x ULN) and renal function (creatinine </= 2.0 mg/dL).
5. Patients must be willing and able to review, understand, and provide written consent before starting therapy.

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), 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. Pregnancy.
5. Acute promyelocytic leukemia (APL).
6. Women of childbearing potential and men who do not practice contraception. Non-childbearing is defined as >/= 1 year postmenopausal or surgically sterilized.
7. Women of childbearing potential and men must agree to use contraception prior to study entry and for the duration of study participation.