Vosaroxin and Infusional Cytarabine in Treating Patients With Untreated Acute Myeloid Leukemia

Inclusion Criteria:

* Ability to provide informed consent
* Ability to tolerate intensive therapy with vosaroxin 90 mg/m\^2 and cytarabine
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2 at time of study entry
* Morphologically confirmed new diagnosis of AML in accordance with World Health Organization (WHO) diagnostic criteria
* Patients who have received hydroxyurea alone or have previously received "non-cytotoxic" therapies for myelodysplastic syndromes (MDS) or myeloproliferative neoplasms (MPN) (e.g., thalidomide or lenalidomide, 5-azacytidine or decitabine, histone deacetylase inhibitors, low-dose Cytoxan, tyrosine kinase or dual tyrosine kinase \[TK\]/SRC proto-oncogene, non-receptor tyrosine kinase \[src\] inhibitors) will be allowed
* Serum creatinine =\< 2.0 mg/dL
* Hepatic enzymes (alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\]) =\< 2.5 x upper limit of normal
* Total bilirubin =\< 1.5 x upper limit of normal unless clearly related to Gilbert's disease, hemolysis or leukemic infiltrate
* FOR PATIENTS IN STAGE 1 (PATIENTS #1-#17)
* \>= 55 years of age with AML of any risk classification, or 18-54 years of age with high-risk AML disease based on one of the following:

  * Antecedent hematologic disorder including myelodysplasia (MDS)-related AML (MDS/AML) and prior myeloproliferative disorder (MPD)
  * Treatment-related myeloid neoplasms (t-AML/t-MDS)
  * AML with FMS-like tyrosine kinase 3 (FLT3) - internal tandem duplication (ITD)
  * Myeloid sarcoma
  * AML with multilineage dysplasia (AML-MLD)
  * Adverse cytogenetics (defined as -5/-5q; -7/-7q; abnormal 3q, 9q, 11q, 20q, 21q or 17p; t(6;9); t(9;22); trisomy 8; trisomy 13; trisomy 21; complex karyotypes (\>= 3 clonal abnormalities); monosomal karyotypes
* FOR PATIENTS IN STAGE 2 (ENROLLED PATIENT #18 AND BEYOND)
* \>= 55 years of age with AML of any risk classification, or 18-54 years of age with intermediate or high risk AML as defined by National Comprehensive Cancer Network (NCCN) risk assignment

Exclusion Criteria:

* STAGES 1 AND 2
* Patients with acute promyelocytic leukemia (APL) as diagnosed by morphologic criteria, flow cytometric characteristics, and rapid cytogenetics or fluorescence in situ hybridization (FISH) or molecular testing
* Any previous treatment with vosaroxin
* Concomitant chemotherapy, radiation therapy

  * For patients with hyperleukocytosis with \> 50,000 blasts/μL; leukapheresis or hydroxyurea may be used prior to study drug administration for cytoreduction at the discretion of the treating physician
* Active, uncontrolled infection

  * Patients with infection under active treatment and controlled with antibiotics, antivirals, or antifungals are eligible
  * Chronic hepatitis is acceptable
* Active, uncontrolled graft vs. host disease (GVHD) following allogeneic transplant for non-AML condition (e.g. MDS, lymphoid malignancy, aplastic anemia); patients with GVHD controlled on stable doses of immunosuppressants are eligible
* Presence of other life-threatening illness
* Left ventricular ejection fraction (LVEF) \< 40% as measured by echocardiogram or multi gated acquisition scan (MUGA)
* Known or suspected central nervous system (CNS) involvement of active AML
* Other active malignancies including other hematologic malignancies or other malignancies within 12 months before randomization, except nonmelanoma skin cancer or cervical intraepithelial neoplasia
* History of myocardial infarction (MI), unstable angina, cerebrovascular accident, or transient ischemic attack (CVA/TIA) within 3 months before randomization
* Prior or current therapy:

  * Hydroxyurea or medications to reduce blast count within 24 hours before randomization
  * Treatment with an investigational product within 14 days before randomization, or not recovered from all acute effects of previously administered investigational products
* Renal insufficiency requiring hemodialysis or peritoneal dialysis
* Pregnant or breastfeeding
* Known human immunodeficiency virus (HIV) seropositivity
* 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
* ADDITIONAL EXCLUSION CRITERIA APPLIED TO STAGE 1
* Patients 18-54 years of age with "good risk" AML defined as the presence of t(8;21), inv(16), or t(16;16) as diagnosed by morphologic criteria, flow cytometric characteristics, and rapid cytogenetics or FISH
* Patients with t(8;21), inv(16), t(16;16) who are unable to receive anthracycline based induction will be allowed to enroll provided the medical reason they are unable to receive anthracyclines is clearly documented and provided they fulfill all other eligibility and criteria