Inclusion Criteria:

• Age >/= 18 years and < 60 years.
• Must be in first relapse of AML, or must receive treatment as first salvage in primary refractory AML; or have high-risk MDS (>/= 10% blasts) with not more than one prior regimen of chemotherapy (therapy with hematopoietic growth factors, biological or targeted therapies are not counted).

Patients in CML myeloid blast phase may receive clofarabine as frontline therapy or in first salvage.

• Total bilirubin </= 2mg/dL, SGPT </= 4 ULN, creatinine </= 2.0mg/dL.
• ECOG performance status </= 2.
• Signed informed consent.
• Male and female patients who are fertile agree to use an effective barrier method of birth control (ie, latex condom, diaphragm, cervical cap, etc) to avoid pregnancy. Female patients need a negative serum or urine pregnancy test within 7 days of study enrollment (applies only if patient is of childbearing potential. Non-childbearing is defined as >= 1 year postmenopausal or surgically sterilized).

Exclusion Criteria:

• Previous treatment with clofarabine.
• Active, uncontrolled, systemic infection considered opportunistic, life threatening, or clinically significant at the time of treatment, or any severe, concurrent disease, which, in the judgment of the investigator and after discussion with the Principal Investigator, would make the patient inappropriate for study entry.
• Symptomatic CNS involvement.
• Patients who receive other chemotherapy. Patients must have been off previous therapy of >/= 2 weeks and must have recovered from acute toxicity of all previous therapy prior to enrollment. Treatment may start earlier following discussion with the Principal Investigator.
• Cardiac ejection fraction </= 30%.