Pevonedistat and Decitabine in Treating Patients With High Risk Acute Myeloid Leukemia

Inclusion Criteria: * Patients diagnosed with acute myeloid leukemia (AML) by World Health Organization (WHO) classification, meeting one of following criteria: * Age 60 or older, newly diagnosed, untreated, who are unwilling to undergo or not candidates for conventional induction chemotherapy with cytarabine/anthracyclines * Age 60 or older with relapsed or refractory disease * Younger adult patients with previously untreated high-risk disease (complex karyotype, inv\[3\] or t\[3;3\], t\[6;9\], monosomal karyotype, therapy-related and secondary disease) that are unwilling to undergo or not candidates for conventional induction chemotherapy with cytarabine/anthracyclines and/or allogeneic stem cell transplantation * Younger patients with refractory/relapsed AML who are otherwise not candidates for allogeneic stem cell transplantation * Patients with extramedullary disease who meet one of the above criteria may be included * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 * Patients with co-morbid medical illness, life expectancy attributed to this must be greater than 6 months * The effects of pevonedistat and decitabine on the developing fetus is unknown; for this reason, women of child bearing potential and men must agree to use effective contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for 4 months following duration of study participation; should a woman become pregnant or suspect that she is…