CPX-351 or CLAG-M Regimen for the Treatment of Acute Myeloid Leukemia or Other High-Grade Myeloid Neoplasms in Medically Less-Fit Patients

- Diagnosis of untreated "high-grade" myeloid neoplasm (>=10% blasts in blood or bone marrow) or AML other than acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) or variants according to the 2016 World Health Organization (WHO) classification. Outside diagnostic material is acceptable to establish diagnosis; submission of peripheral blood specimen for flow cytometry performed at the study institution should be considered. Diagnostic material must have been submitted for cytogenetic and/or molecular testing as clinically appropriate

- Treatment-related mortality (TRM) score >= 13.1 as calculated with simplified model

- The use of hydroxyurea before enrollment is permitted; hydroxyurea should be discontinued prior to start of study treatment. Patients with symptoms/signs of hyperleukocytosis or white blood cells (WBC) > 100,000/uL or with concern for other complications of high tumor burden or leukostasis (e.g. hypoxia, disseminated intravascular coagulation) can be treated with leukapheresis or may receive up to 2 doses of cytarabine (up to 500 mg/m^2) any time prior to enrollment

- Patients may have received low-intensity treatment (e.g. azacitidine/decitabine, lenalidomide, growth factors) for antecedent low-grade myeloid neoplasm (i.e. < 10% blasts in blood and bone marrow)

- Bilirubin < 2.0 mg/mL unless elevation is thought to be due to hepatic infiltration by neoplastic cells, Gilbert's syndrome, or hemolysis (assessed within 14 days prior to study day 0)

- Left ventricular ejection fraction (LVEF) >= 45%, assessed within 12 months prior to registration, e.g. by multigated acquisition scan (MUGA) scan or echocardiography or another appropriate diagnostic modality

- Women of childbearing potential and men must agree to use adequate contraception beginning at the signing of the consent until at least 4 weeks after the last dose of study drug

- Ability to understand and the willingness to sign a written informed consent document

- Myeloid blast crisis of chronic myeloid leukemia (CML), unless patient is not considered candidate for tyrosine kinase inhibitor treatment

- Concomitant illness associated with a likely survival of < 1 year

- Active systemic fungal, bacterial, viral, or other infection, unless disease is under treatment with anti-microbials and/or controlled or stable. Patients with fever thought to be likely secondary to leukemia are eligible

- Known hypersensitivity to any study drug used in this trial

- Pregnancy or active breast feeding

- Concurrent treatment with any other approved or investigational anti-leukemia agent. Treatment with a FLT3-inhibitor for FLT3-mutated AML is permissible