Methylation is a change that occurs to DNA that has an effect on gene usage in human cells. Abnormal methylation is very common in leukemias. Decitabine is a new drug that blocks DNA methylation. The goal of this clinical research study is learn if decitabine (given at 3 different doses) can help to control MDS. The safety of these 3 treatments will also be studied.

Since decitabine is effective in MDS, we would like to continue investigating its activity, correlate methylation profiles with response, and improve on the efficacy: toxicity profile of the regimen. Preclinical studies indicate that longer exposure to decitabine is more active since the drug has to integrate into one, then the second DNA strand, before inducing the full hypomethylating effect. Therefore, an exposure of > 5 days (rather than the 3-day schedule used in MDS by Wijermans et al) may be better. On the other hand, it is yet unknown whether a longer exposure (10 days versus 5 days) would be clinically even more effective,and whether it would have more side-effects if the total dose of decitabine per course is the same. A subcutaneous decitabine schedule in MDS will also have multiple advantages (quality of life, less catheter-related infections, less hospital environment) in addition to possible better pharmacokinetic profile and better efficacy. We thus propose to investigate, in a phase II randomized study, the comparative efficacy and toxicity of three different schedules of decitabine which deliver the same total dose of the drug per course: 1) decitabine 10 mg/m2 IV over 1 hour daily x 10; versus 2) decitabine 20 mg/m2 IV over 1 hour daily x 5 (total 100 mg/m2 per course); versus 3) decitabine 10 mg/m2 SQ BID x 5 days (20 mg/m2/day x 5 = 100 mg/m2 per course).

Genders Eligible for Study:  Both

Criteria

Eligibility Criteria:

• Patients with MDS and > 5% blasts or IPSS risk intermediate or high; patients with CMML. No prior intensive chemotherapy or high-dose ara-C (> 1g/m2). Prior biologic therapies, targeted therapies, or single agent chemotherapy allowed. Patients must have been off chemotherapy for 2 weeks prior to entering this study and recovered from the toxic effects of that therapy, unless there is evidence of rapidly progressive disease. Hydroxyurea is permitted for control of counts prior to treatment. Procrit, GCSF are allowed before therapy. Procrit, GCSF or other growth factors are permitted on therapy. Use of hydroxyurea with rapidly proliferative disease is allowed for the first two weeks on therapy.
• Performance 0-2 (ECOG). Adequate liver function (bilirubin of < 2mg/dl) and renal function (creatinine < 2mg/dl). Adequate cardiac functions (NYHA cardiac III-IV excluded)
• Signed informed consent

Exclusion Criteria

• Nursing and pregnant females. Patients of childbearing potential should practice effective methods of contraception. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Active and uncontrolled infections.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.