The goal of this clinical research study is to learn if the combination of vosaroxin and decitabine can help to control AML or MDS. The safety of these drugs will also be studied.
Inclusion Criteria: 1. Previously untreated AML (\>/= 20% blasts). Patients with high-risk MDS (defined as having \>/= 10% blasts in the bone marrow) or patients with Chronic Myelomonocytic Leukemia (CMML) (having \>/= 10% blasts in the bone marrow) may also be eligible after discussion with Principal Investigator (PI). Prior therapy with hydroxyurea, biological or targeted therapy (e.g. FLT3 inhibitors, other kinase inhibitors), or hematopoietic growth factors is allowed, however prior therapy with chemotherapy agents for the disease under study is not allowed. Patients may have received one dose of cytarabine (up to 2 g/m2) administered at presentation for control of hyperleucocytosis. For patients with prior MDS or CMML who transformed to AML, therapy received for MDS is not considered as prior therapy for AML. 2. Age \>/= 60 years and not candidates for conventional cytotoxic chemotherapy or refuse it; OR patients below the age of 60 years who are considered unfit and/or unable to tolerate standard chemotherapy at the discretion of the treating physician or the principal investigator. " 3. Eastern Cooperative Oncology Group performance status \</= 2. 4. Adequate hepatic (serum total bilirubin \</= 1.5 x upper limit normal (ULN), alanine aminotransferase and/or aspartate transaminase \</= 2.5 x ULN) and renal function (creatinine \</= 2.0 mg/dL). 5. Left ventricular ejection fraction (LVEF) at least 40% by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) 6. Patients must be willing and able to review, understand, and provide written consent before starting therapy. 7. Females must be surgically or biologically sterile or postmenopausal (amenorrheic for at least 12 months) or if of childbearing potential, must have a negative serum pregnancy test within 14 days before the start of the treatment. Women of childbearing potential may have a urine pregnancy test, instead of a serum pregnancy test. If either the serum or urine pregnancy test is equivocally negative the patient will be eligible for the protocol. Women of childbearing potential must agree to use an adequate method of contraception during the study until 30 days after the last treatment. Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 30 days after the last treatment. Exclusion Criteria: 1. New York Heart Association class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition such as active angina pectoris, clinically significant cardiac arrhythmia that requires therapy in the opinion of the treating physician or PI, uncontrolled hypertension (blood pressure \> 160 systolic and \> 110 diastolic not responsive to antihypertensive medication), uncontrolled diabetes mellitus in the opinion of the treating physician or PI, or uncontrolled congestive heart failure in the opinion of the treating physician or PI. 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. Pregnant or breastfeeding 5. Known Human Immunodeficiency Virus seropositivity 6. Any other medical, psychological, or social condition that may interfere with study participation or compliance, or compromise patient safety in the opinion of the investigator or medical monitor 7. Acute promyelocytic leukemia (APL).