Decitabine and Clofarabine in Higher Risk Myelodysplastic Syndromes (MDS)

Inclusion Criteria:

1. Patients with higher risk MDS (IPSS int-2 or high, or >/= 10% blasts as defined by WHO or FAB). - No prior intensive chemotherapy or high-dose cytarabine (>/= 1 g/m2). - Prior biologic therapies (</= 1 cycle of prior decitabine or azacitidine), targeted therapies, or single agent chemotherapy is allowed. - Off chemotherapy for 2 weeks prior to entering this study with no toxic effects of that therapy, unless there is evidence of rapidly progressive disease. - Hydroxyurea is permitted for control of counts prior to treatment. - Hematopoietic growth factors are allowed.
2. Age >/= 18 years.
3. ECOG performance status </= 2.
4. Have adequate renal function (serum creatinine </= 1.5 mg/dL)
5. Serum bilirubin </= 1.5 x upper limit of normal (ULN)
6. Aspartate transaminase (AST) or alanine transaminase (ALT) </= 2.5 x ULN
7. Alkaline phosphatase </= 2.5 x ULN
8. Provide signed written informed consent.
9. Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent.
10. Female patients of childbearing potential must have a negative pregnancy test within 2 weeks prior to enrollment.
11. Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.

Exclusion Criteria:

1. Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.
2. Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea. The patient must have recovered from all acute toxicities from any previous therapy.
3. Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment.
4. Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment)
5. Pregnant or lactating patients.
6. Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results
7. Any concurrent malignancy (with the exception of exclusion # 8)
8. Exceptions to inclusion # 7: a) Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed; b) Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values are also eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed.