Decitabine and Clofarabine in Higher Risk Myelodysplastic Syndromes (MDS)

The Study Drugs: Decitabine is designed to damage cells' DNA (genetic material), which may cause myelodysplastic marrow cells to work more like normal marrow cells. Clofarabine is designed to interfere with the growth and development of abnormal marrow cells. Study Groups: If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 groups. * If you are in Group 1, you will receive decitabine and clofarabine. * If you are in Group 2, you will receive only decitabine. Study Drug Administration: Each cycle is 4-8 weeks depending on how you tolerate the drug and how the MDS responds to it. Group 1: If you are in Group 1, you will receive the drugs in an alternating series of cycles. This means that you will receive decitabine for the first 3 cycles, then clofarabine for the next 3 cycles, and then repeat. This pattern will continue for up to 24 cycles. On Days 1-5 of Cycles 1-3, 7-9, 13-15, and 19-21, you will receive decitabine by vein over 1-2 hours. On Days 1-5 of Cycles 4-6, 10-12, 16-18, and 22-24, you will receive clofarabine by vein over 1-2 hours. Group 2: If you are in Group 2, you will receive decitabine by vein over 1-2 hours on Days 1-5 of every cycle. Study Visits: On Day 1 of every cycle, the following tests and procedures will be performed: * You will have a physical exam, including measurement of your weight and vital signs. * Your performance status will be recorded. Once a week, blood (about 1-2 teaspoons) will be drawn for routine tests. At the end of Cycle 3, you will have a bone marrow aspirate to check the status of the disease. If the disease has not gone into remission after Cycle 3, your next bone marrow aspirate will depend on your group. If you are in Group 1, you may have another aspirate about 3 weeks after you begin Cycle 4. After that, you may have an aspirate every 2 weeks (or more often if your doctor feels it is needed) until the response (or lack thereof) is confirmed. If you are in Group 2, you may not have another bone marrow aspirate until after the end of Cycle 6. You will need to stay in Houston to receive the study drug(s). When you have study visits where you are not receiving study drug(s), these tests can be performed by your local doctor. If your MD Anderson leukemia doctor approves, your study drug can be administered outside MD Anderson by your local doctor. Length of Study: You will be on study for up to 24 cycles. You will be taken off study early if the disease gets worse or you experience any intolerable side effects. Follow-up Visits: After your last dose of study drug, you will have follow-up visits. You will only have these visits if the disease has responded to the study drug. * Once a month, blood (about 1 tablespoon) will be drawn routine tests. This can be done at home through your local cancer doctor. * Every 6 months, you will return to Houston for a physical exam and blood (about 1 tablespoon) will be drawn for routine tests. This is an investigational study. Clofarabine is FDA approved and commercially available for use in pediatric patients with a type of blood cancer (acute lymphocytic leukemia -- ALL). Its use in patients with MDS is investigational. Decitabine is FDA approved and commercially available for use in patients with MDS. Up to 80 patients will take part in this study. All will be enrolled at MD Anderson.