CPX-351 in Treating Patients With Newly Diagnosed, High-Risk Acute Myeloid Leukemia

This phase II trial studies the best dose and how well liposomal cytarabine-daunorubicin CPX-351 (CPX-351) works in treating patients with newly diagnosed acute myeloid leukemia and who are at risk for not responding well to treatment. Liposomal cytarabine-daunorubicin CPX-351 combines two chemotherapy drugs that are known to help each other work better, and may work to stop the growth of cancer cells by blocking the cells from dividing.

Inclusion Criteria: * Ability to understand and voluntarily sign an informed consent form * Pathological diagnosis of AML according to World Health Organization (WHO) criteria (with at least 20% blasts in the peripheral blood or bone marrow): newly diagnosed de novo AML; except for acute promyelocytic leukemia (APL); newly diagnosed secondary AML, defined as having a history of an antecedent hematologic disorder (myelodysplastic syndromes \[MDS\], myeloproliferative disease \[MPD\] or history of cytotoxic treatment for non-hematologic malignancy) or apparent de novo AML with MDS-associated karyotype * Eastern Cooperative Oncology Group (ECOG) performance status 0-3 * Serum creatinine =\< 2.0 mg/dL * Serum total bilirubin =\< 2.0 mg/dL * Serum alanine aminotransferase \< 3 times the upper limit of normal (ULN); Note: If elevated liver enzymes are related to disease alanine aminotransferase (ALT) should be \< 5 times ULN * To be considered at high risk for induction mortality patients must have 1 or 2 of the following risk factors (patients \>= 60 must have at least 1 risk factor, patients \< 60 must have at least 2 risk factors) present; at least one risk factor in every patient must be an AML-related factor: * AML-related factors include: * Antecedent hematologic disorder (AHD) (MDS, chronic myelomonocytic leukemia \[CMML\], or MPD) or history of exposure to cytotoxic chemotherapy \[therapy-related (t)-AML\]), or WHO-defined AML with MDS-related changes or apparent de novo AML with MDS-associated karyotype * Unfavorable cytogenetics as defined by the European Leukemia Net * Patient-related factors: * Age \>= 70 * ECOG performance status (PS) \>= 2 * Co-morbidities: * Serum creatinine \> 1.3 g/dL * Cardiac ejection fraction \>= 50% by echocardiography or multi gated acquisition (MUGA) (when left ventricular ejection fraction \[LVEF\] expressed as a range, at least the upper limit should include 50%) * Able to adhere to the study visit schedule and other protocol requirements * All men and women must agree to practice effective contraception during the study period if not otherwise documented to be infertile Exclusion Criteria: * Patients with history of second malignancy are eligible if they have documentation of disease stability, off therapy, based on computed tomography (CT) scan or other measures for the 6 months prior to entry in core * Any serious medical condition or psychiatric illness that would prevent the patient from providing informed consent * Chemotherapy or other investigational anticancer therapeutic drugs in the two weeks prior to study entry; in the event of rapidly proliferative disease, however, the use of hydroxyurea is permitted up to 24 hours before study entry in core * Evidence of active central nervous system (CNS) leukemia * Pregnant or lactating women * Uncontrolled infection; to be eligible, patients receiving treatment for an infection (antibiotic, antifungal or antiviral treatment) must be afebrile (\< 38.3 degrees Celsius \[C\]) and without hemodynamic instability or dyspnea from pneumonia for \> 48 hours (hrs) prior to the start of induction therapy * Hypersensitivity to cytarabine, daunorubicin or liposomal products * History of Wilson's disease or other copper-metabolism disorder