AR-42 and Decitabine in Treating Patients With Acute Myeloid Leukemia

Inclusion Criteria: * Adult patients (stratum 1) must be age \>= 18 with relapsed or refractory acute myeloid leukemia (AML) or age \>= 60 with previously untreated AML who are not candidates for or refuse standard/conventional induction chemotherapy (e.g. the 7+3 combination of cytarabine and an anthracycline); pediatric patients, age 3 to \< 18 years (stratum 2) will be eligible with AML in second relapse or with refractory disease * Patients with secondary AML or therapy related disease (t-AML) are eligible * Patients who received decitabine or 5-azacitidine as prior treatment for myelodysplastic syndrome (MDS) (or AML) remain eligible for the dose escalation phase of the study; however, neither of these agents is permitted within 3 months of study entry; patients who have received prior decitabine or 5- azacitidine will be excluded from the expansion phase of the trial * If the patient has co-morbid medical illness, life expectancy attributed to this must be greater than 6 months * Performance status: Adults (\>= 18 years) must be Eastern Cooperative Oncology Group (ECOG) performance status =\< 2; pediatric patients (\< 18 years) must be at least Lansky \> 50% * 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 (adults \> 18 years); \< 1.3 x upper limit normal for age (pediatric patients \< 18 years) * New York Heart Association (NYHA) congestive heart failure (CHF) class II or better * The effects of decitabine and AR-42 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, both men and women must agree to use adequate contraception (barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; if the patient does not agree, the patient is not eligible; should a woman become pregnant or suspect she is pregnant while participating in the study, she should inform her treating physician immediately * Ability to understand and willingness to sign the written informed consent document * Patients must have recovered from the toxicity of prior therapy to less than grade 2 Exclusion Criteria: * Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study; hydroxyurea may be administered for control of leukocytosis both pre-treatment and during cycle 1 only * Patients receiving any other investigational agents or patients that have received other investigational agents within 28 days of enrollment * Patients with active central nervous system disease or with a single granulocytic sarcoma as sole site of disease * Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to decitabine or AR-42 that cannot be managed with oral antihistamines, antipyretics (ie. acetaminophen) or low dose corticosteroids (\< 10 mg oral prednisone or equivalent corticosteroid) * 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; as infection is a common feature of AML, patients with active infection are permitted to enroll provided that the infection is under control; myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, uncontrolled hypertension, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities * Patients with serious medical or psychiatric illness likely to interfere with participation in this clinical study * Patients with a known confirmed diagnosis of human immunodeficiency virus (HIV) infection (due to concern for increased toxicity with the regimen in combination with highly active antiretroviral therapy \[HAART\]) * Patients with a known diagnosis of chronic hepatitis B infection (ie. persistence of hepatitis B surface antigen in the blood for 6 months or longer) or a diagnosis of hepatitis C (ie. the presence of anti-hepatitis C (hepatitis C virus \[HCV\]) antibodies in the peripheral blood) are excluded; patients with a recent diagnosis (\< 6 months) of active viral hepatitis B or C are excluded * Patients who have advanced malignant solid tumors at the time of consideration for enrollment on this trial are excluded; patients who have a history of an advanced malignant solid tumor, but have no evidence of disease at the time of consideration for enrollment, are eligible * Patients with a known impairment of gastrointestinal (GI) function due to a GI disease such as inflammatory bowel disease (Crohn's disease, ulcerative colitis) or celiac disease, that may significantly alter the absorption of AR-42 are excluded * Pregnant women or women who are breastfeeding are excluded from this study; confirmation that the subject is not pregnant must be established by a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test result obtained during screening; pregnancy testing is not required for post-menopausal or surgically sterilized women * Diagnosis of prolonged QT syndrome * Patients with a mean corrected QT interval (QTc) \> 450 msec in males and \> 470 msec in females * Inability to swallow capsules