Decitabine, Vorinostat, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome

Exclusion Criteria

• •Patients with relapsed or refractory high risk MDS (defined as International Prognostic Scoring System \[IPSS\] score \>= 1.5) will also be eligible; IPSS score can be calculated any time from myelodysplastic syndrome (MDS) diagnosis at relapse/treatment failure for the purposes of trial eligibility
• •Patients with secondary AML or therapy related disease (t-AML) are eligible; patients who received decitabine or 5-azacytidine as prior treatment for MDS (or AML) are eligible; patients who previously received high dose cytarabine (\>= 1 gm/m\^2/dose) are eligible
• •If the patient has co-morbid medical illness, life expectancy attributed to this must be greater than 6 months
• •Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• •Total bilirubin \< 2.0 mg/dL
• •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) \< 2.5 X institutional upper limit of normal
• •Creatinine \< 2.0 mg/dL
• •New York Heart Association (NYHA) congestive heart failure (CHF) class II or better
• •Ability to understand and willingness to sign the written informed consent document
• •Patients with known human immunodeficiency virus (HIV) infection without a history of acquired immune deficiency syndrome (AIDS) and with sufficiently high cluster of differentiation (CD)4 cells (\> 400/mm\^3) and low HIV viral loads (\< 30,000 copies/ml plasma) not requiring anti-HIV therapy are eligible
• •Patients must have recovered from the toxicity of prior therapy to less than grade 2
• •Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study, or those who have not recovered from adverse events (to less than grade 2) due to agents administered more than 4 weeks earlier
• •Patients may not have taken valproic acid, or any other histone deacetylase inhibitor, for at least 2 weeks prior to study enrollment
• •Patients receiving any other investigational agents or patients that have received other investigational agents within 14 days of enrollment
• •Patients with active central nervous system disease or with granulocytic sarcoma as sole site of disease
• •Patients with history of medically serious allergic reactions attributed to decitabine, vorinostat, or cytarabine or compounds of similar chemical or biologic composition that are not easily managed
• •Patients with the following will be excluded: uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) class III or IV heart failure, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; patients with medical comorbidities that will preclude safety evaluation of the combination should not be enrolled
• •Patients with serious medical or psychiatric illness likely to interfere with participation in this clinical study
• •Pregnant women or women who are breastfeeding; breastfeeding should be discontinued; confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening; pregnancy testing is not required for post-menopausal or surgically sterilized women
• •Patients with advanced malignant solid tumors are excluded; patients with active additional hematologic malignancies are excluded
• •Patients with a history of neurologic toxicity with cytarabine or vorinostat are excluded
• •Patients with active infection are permitted to enroll provided that the infection is under control; patients with uncontrolled infection shall not be enrolled until infection is treated and brought under control
• •Patients who are unable to swallow pills are excluded
• •Patients requiring warfarin are excluded