A Phase 1 Study of AOH1996 in Patients With Relapsed/Refractory Acute Myeloid Leukemia

Inclusion Criteria: * Documented informed consent of the participant and/or legally authorized representative * Age: ≥ 18 years * Eastern Cooperative Oncology Group (ECOG) ≤ 2 * Life expectancy \> 3 months * Patients with histologically confirmed AML, according to International Consensus Classification (ICC) or World Health Organization (WHO) criteria, with refractory/relapsed (R/R) disease who have failed treatment with, or are ineligible for, available therapies known to be effective for treatment of their AML * Patients with extramedullary disease may be included if they also have marrow involvement * Patients with acute promyelocytic leukemia (APL) will not be eligible * Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 to prior anti-cancer therapy * Ability to swallow pills * White blood cell (WBC) ≤ 25 x 10\^9/L prior to initiation of study therapy. Cytoreduction with hydroxyurea prior to treatment and/or during cycle 1 may be required (within 14 days prior to day 1 of protocol therapy) * Total bilirubin ≤ 1.5 X upper limit of normal (ULN) (within 14 days prior to day 1 of protocol therapy) * Aspartate aminotransferase (AST) =\< 3.0 x ULN (within 14 days prior to day 1 of protocol therapy) * Alanine aminotransferase (ALT) =\< 3.0 x ULN (within 14 days prior to day 1 of protocol therapy) * Creatinine clearance of ≥ 50 mL/min per 24 hour urine test or the Cockcroft-Gault formula (within 14 days prior to day 1 of protocol therapy) * International normalized ratio (INR) OR prothrombin (PT) ≤ 1.5 x ULN (within 14 days prior to day 1 of protocol therapy) * Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN (within 14 days prior to day 1 of protocol therapy) * Corrected QT interval (QTc)F ≤ 480 ms based on Fridericia's formula * Note: To be performed within 28 days prior to day 1 of protocol therapy * Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (within 14 days prior to day 1 of protocol therapy) * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required * Agreement by females and males of childbearing potential\* to use an effective method of birth control (nonhormonal) or abstain from heterosexual activity for the course of the study through at least 2 months after the last dose of protocol therapy * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only) Exclusion Criteria: * Hematopoietic stem cell transplant within 100 days prior to day 1 of protocol therapy. Patients who have stopped calcineurin inhibitors (CNI) must be off CNIs for at least 2 weeks prior to day 1 of protocol therapy * Chemotherapy, radiation therapy, biological therapy, immunotherapy within 14 days prior to day 1 of protocol therapy with the following exception of hydroxyurea which is allowed prior to treatment and through cycle 1 for control of rapidly progressing leukemia * Strong inducers or strong inhibitors of CYP enzymes (e.g., 1A2, 2B6, 2C8, 2C9, 2C19, and 3A4), other than azole antifungals with CYP3A4 inhibition potential, or drug transporters (e.g., organic anions \[OATP1B1/1B3\], BCRP, P-gp, organic cations \[OCT1, OCT2, OCT3\], MATE1 or MATE2K), or sensitive substrates of these CYPs or drug transporters, within 4-5 half-lives or 14 days prior to the first dose of study drug, whichever is longer. * Foods/supplements that are strong inhibitors or strong or moderate inducers of CYP3A (such as St. John's wort) within 3 days prior to initiation of and during study treatment * Systemic steroid therapy \> 10 mg/day (≤ 10mg/day prednisone equivalent ok) or any other form of immunosuppressive medication within 14 days. Inhaled or topical steroids, and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent, are permitted * Must not have received or planning to receive live vaccine while being on study or 4 weeks before and after completion of treatment * Patients with blast phase chronic myeloid leukemia (CML) * Patients with translocation (t)(15;17) karyotypic abnormality or acute promyelocytic leukemia (French-American-British \[FAB\] class M3-AML) * Active central nervous system (CNS) disease * Active graft versus (vs) host disease (GVHD) * Unstable cardiac disease as defined by one of the following: * Cardiac events such as myocardial infarction (MI) within the past 6 months * Uncontrolled atrial fibrillation or hypertension * No measurable disease in the bone marrow * Gastrointestinal disorder that interferes with oral drug absorption such as malabsorption syndrome * History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent * Uncontrolled active infection * Clinically significant uncontrolled illness * Other active malignancy. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial * Females only: Pregnant or breastfeeding * Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures * Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)