Tosedostat in Combination With Cytarabine or Decitabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

Inclusion Criteria: * Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent * All adults \>= 60 years of age with untreated AML or high-risk MDS (10-19% marrow blasts) including those with prior myelodysplasia (MDS)/AML, therapy-related AML, AML with trilineage dysplasia (AML-TLD), and AML with adverse cytogenetics; patients may be enrolled if they received prior treatment with hydroxyurea to control blood counts or demethylating agents specifically for the purpose of treating MDS * Adults age 18 to 59 with untreated AML or high-risk MDS and a transplant-related mortality (TRM) score of \>= 9.2; previous data suggests these people would have a 25% mortality with standard therapy, making this treatment a reasonable alternative * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 - 2 * Serum creatinine =\< 2.0 mg/dL; if serum creatinine \> 2.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be \> 50 mL/min/1.73 m\^2 as calculated by the Modification of Diet in Renal Disease equation * Serum bilirubin =\< 1.5 × upper limit of normal (ULN) (in the absence of Gilbert's syndrome) * Aspartate transaminase (AST)/alanine transaminase (ALT) =\< 3.0 × ULN * Alkaline phosphatase =\< 2.5 × ULN * Male subjects, even if surgically sterilized (i.e., status postvasectomy) must agree to 1 of the following: practice effective barrier contraception during the entire study treatmen…