STAT Inhibitor OPB-111077, Decitabine and Venetoclax in Treating Patients With Acute Myeloid Leukemia That Is Refractory, Relapsed or Newly Diagnosed and Ineligible for Intensive Chemotherapy

Prior treatment

• Subjects must not be receiving any chemotherapy agents (except hydroxyurea); intrathecal methotrexate and cytarabine are permissible
• Subjects must not be receiving growth factors, except for erythropoietin
• Subjects with other severe concurrent disease which in the judgment of the investigator would make the patient inappropriate for entry into this study are ineligible
• Subjects must not have received any investigational agents within 14 days or 5 half-lives (whichever is longer) of study entry
• Subjects must not be pregnant or breastfeeding; pregnancy tests must be obtained for all females of child-bearing potential; pregnant or lactating patients are ineligible for this study; males or women of childbearing potential may not participate unless they have agreed to use an effective contraceptive method (defined as hormonal contraceptives, intrauterine devices, surgical contraceptives, or condoms)
• Subjects who have uncontrolled infection are not eligible; patients must have any active infections under control; fungal disease must be stable for at least 2 weeks before study entry
• Subjects with bacteremia must have documented negative blood cultures prior to study entry
• Subjects who are suitable for and willing to receive standard intensive induction therapy
• Subjects who are candidates for allogeneic transplantation, have a suitable donor, and are willing to undergo transplantation

Other illness

• Subjects with a "currently active" second malignancy, other than non-melanoma skin cancer, carcinoma in situ of the cervix, resected incidental prostate cancer (staged pT2 with Gleason score =\< 6 and postoperative prostate-specific antigen \[PSA\] \< 0.5 ng/mL), or other adequately treated carcinoma-in-situ are ineligible; patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for \>= 1 year
• Subjects with uncontrolled high blood pressure, unstable angina, symptomatic congestive heart failure (New York Heart Association \[NYHA\] class 3), myocardial infarction within the past 6 months or serious uncontrolled cardiac arrhythmia are not eligible

Other

• Subjects with FAB M3 (t(15;17)(q22;q21)\[PML-RARalpha\]) are not eligible
• Subjects must not have evidence of active leukemia in the central nervous system (CNS)

• Patients must have histologic evidence of high risk acute myeloid leukemia defined as one of the following:
  • Non-M3 AML refractory to standard primary induction therapy
  • Non-M3 AML relapsed after (i) any standard induction therapy (ii) any number of standard or experimental salvage therapies
  • Newly diagnosed non-M3 AML not eligible for intensive induction chemotherapy
• Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
• Subjects must have a life expectancy of at least 4 weeks
• Subjects must be able to consume oral medication
• Subjects must have recovered from the toxic effects of any prior chemotherapy to= \< grade 1 (except alopecia)
• Creatinine clearance (CrCL) \>= 45
• Total bilirubin =\< 2 x upper limit of normal (ULN)
• Serum glutamate pyruvate transaminase (SGPT) alanine aminotransferase (ALT) =\< 2 x ULN
• Negative pregnancy test for women with child-bearing potential
• Patients must be able to sign consent and be willing and able to comply with scheduled visits, treatment plan and laboratory testing