Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed acute myeloid leukemia

          -  Patients must have an 11q23 translocation or partial tandem duplication, confirmed by
             cytogenetics, fluorescence in situ hybridization (FISH), or myeloid panel. Both de
             novo and therapy-related acute myeloid leukemia (AML) with an 11q23 rearrangement or
             partial tandem duplication (PTD) are considered eligible

          -  Patients may not have any other targetable mutations (such as FLT3, IDH1, and IDH2)
             identified on myeloid mutational panel testing or must refuse treatment with a
             targeted agent if such a mutation is detected

          -  Eastern Cooperative Oncology Group (ECOG) performance status < 3 (Karnofsky > 60%)

          -  Prothrombin time (PT) and activated partial thromboplastin time (aPTT) =< 1.5 x upper
             limit of normal (ULN)

          -  Total bilirubin < 2 times the upper limit of institutional normal (ULN) unless due to
             Gilbert's disease

          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =<
             2.5 x institutional upper limit of normal

          -  Creatinine =< 2 times the upper limit of institutional normal (ULN) OR creatinine
             clearance glomerular filtration rate (GFR) >= 30 mL/min/1.73 m^2

          -  Patients treated in the up-front setting must decline standard-of-care therapy

          -  Ability to understand and the willingness to sign a written informed consent document.
             Participants with impaired decision-making capacity with a close legal
             guardian/caregiver may be considered

          -  Patients must have measurable disease, defined as abnormal blasts detectable in the
             peripheral blood or bone marrow or the presence of extramedullary disease, including
             leukemia cutis. Patients with extramedullary disease but no bone marrow disease are
             still considered eligible

          -  Patients may have had previous treatment with standard-of-care or experimental agents.
             Patients who have previously undergone bone marrow transplantation may also be
             included

          -  Patients who are human immunodeficiency virus (HIV) positive (+), hepatitis B virus
             (HBV)+, and/or hepatitis C virus (HCV)+ may be eligible as follows:

               -  Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral
                  therapy with undetectable viral load within 6 months are eligible for this trial.
                  The antiretroviral therapy should not strongly induce or inhibit CYP3A4

               -  If evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be
                  undetectable on suppressive therapy if indicated

               -  If history of hepatitis C virus (HCV) infection, must be treated with
                  undetectable HCV viral load

          -  The effects of pinometostat on the developing human fetus are unknown. For this reason
             and because histone methyltransferase inhibitors as well as hypomethylating agents are
             known to be teratogenic, women of child-bearing potential and 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 and for 4 weeks after the
             last dose of study treatment. Should a woman become pregnant or suspect she is
             pregnant while she or her partner is participating in this study, she should inform
             her treating physician immediately. Men treated or enrolled on this protocol must also
             agree to use adequate contraception prior to the study, for the duration of study
             participation, and 90 days after completion of pinometostat and azacitidine
             administration

        Exclusion Criteria:

          -  Patients who are receiving any other investigational agents

          -  Patients with active central nervous system (CNS) disease are excluded from this
             clinical trial because they may develop progressive neurologic dysfunction that would
             confound the evaluation of neurologic and other adverse events. Patients with a prior
             history of CNS disease will not be excluded

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to pinometostat or azacitidine

          -  Patients receiving any medications or substances that are inhibitors or inducers of
             the CYP3A4 or CYP450 system should have their medications reviewed and adjusted for
             interactions as appropriate for local institutional practice. Because the lists of
             these agents are constantly changing, it is important to regularly consult a
             frequently-updated medical reference. As part of the enrollment/informed consent
             procedures, the patient will be counseled on the risk of interactions with other
             agents, and what to do if new medications need to be prescribed or if the patient is
             considering a new over-the-counter medicine or herbal product

          -  Patients receiving any medications or substances that are inhibitors or inducers of
             MATE1 and MATE2-K transporters should have their medications reviewed and adjusted for
             interactions as appropriate for local institutional practice. Pinometostat has been
             demonstrated to be an inhibitor of MATE1 and MATE2-K transporters in vitro, although
             the clinical significance of this is unclear. Drug interactions may occur between
             pinometostat and other therapies that are MATE substrates, including metformin.
             Consultation with a frequently updated medical reference and/or pharmacist should be
             sought to guide necessary changes in the patient's other medications

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris,
             uncontrolled or clinically significant cardiac arrhythmia, or psychiatric
             illness/social situations that would limit compliance with study requirements.
             Patients with these conditions that are medically well controlled may be considered
             for enrollment

          -  Pregnant women are excluded from this study because pinometostat is an agent with the
             potential for teratogenic or abortifacient effects. Because there is an unknown but
             potential risk for adverse events in nursing infants secondary to treatment of the
             mother with pinometostat, breastfeeding should be discontinued if the mother is
             treated with pinometostat. These potential risks may also apply to other agents used
             in this study

          -  HIV-positive patients on combination antiretroviral therapy should have their regimen
             reviewed for potential pharmacokinetic interactions with pinometostat and azacitidine.
             In the event of a potential interaction, alternative therapies may be considered in
             consultation with the patient's primary HIV physician

          -  Absence of an 11q23 rearrangement or absence of an 11q23 partial tandem duplication

          -  Patients with an active bleeding diathesis

          -  Patients at increased risk of QT prolongation (e.g. from known long-QT syndrome) or
             who have a corrected QT interval that is persistently longer than 450 ms despite
             adjustments to other medications

          -  Patients who are eligible for or willing to receive intensive induction therapy for de
             novo AML