Azacitidine, Mitoxantrone Hydrochloride, and Etoposide in Treating Older Patients With Poor-Prognosis Acute Myeloid Leukemia

Inclusion Criteria: * Acute myeloid leukemia (AML) as defined by World Health Organization (WHO) criteria, any subtype, de novo or secondary, except acute promyelocytic leukemia (APL) * One of the following: * Previously untreated, with adverse-risk cytogenetics, including any one of the following: * Complete or partial deletion of chromosome 7 * Complete or partial deletion of chromosome 5 * At least 3 numerical or structural abnormalities, other than t(15;17), t(8;21) or inv(16) or variant * 11q23 abnormalities * Inv(3) or variant such as t(3:3) * Previously untreated, transformed from prior myelodysplastic syndrome (MDS) or myeloproliferative disorder (MPD) other than CML * Persistent leukemia following one cycle of 3+7 induction therapy (cytarabine plus either daunorubicin or idarubicin), any cytogenetic risk group * Left ventricular ejection fraction (LVEF) \> 50% based on multi gated acquisition scan (MUGA) scan or 2-dimensional (2-D) echocardiogram * Serum creatinine =\< 1.5 x upper limit of normal (ULN) * Serum bilirubin =\< 1.5 x ULN * Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x ULN * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnofsky \>= 60%) * Patients with high initial white blood cell (WBC) should have the WBC reduced to below 50 x 10\^9/L with hydroxyurea, to minimize the risk of leukostasis related-complications; hydroxyurea is permitted up to 24 hours prior to starting azacitidine * Men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; men should not father a child while participating in this study * Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: * Patients who have had chemotherapy, radiotherapy or investigational agents within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier * Patients who have received prior radiation greater than 3000 cGy to marrow producing areas * Patients may not be receiving any other investigational agents * Patients with active central nervous system (CNS) leukemia; prior CNS leukemia is permitted provided the cerebrospinal fluid has cleared and there is no other evidence of active CNS leukemia * Prior therapy for AML with decitabine, azacitidine, mitoxantrone, or etoposide * Prior therapy with azacitidine or decitabine for pre-existing MDS * History of allergic reactions attributed to decitabine, azacitidine, etoposide, mitoxantrone, or compounds of similar chemical or biologic composition * Uncontrolled intercurrent illness including, but not limited to, active uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Human immunodeficiency virus (HIV)-positive patients with cluster of differentiation (CD) counts less than 500/mm\^3 and/or a history of HIV/acquired immune deficiency syndrome (AIDS)-related complications will be excluded from the study