Leukemia Clinical Trials

• Age 18 and older

• Subjects with evidence of AML that meet at least one of the following criteria:

‣ Relapsed AML: as evidence by ≥5% myeloblasts in the bone marrow, or reappearance of blasts in the peripheral blood

⁃ Refractory AML: ≤2 prior induction regimens (example: patients who receive 7 + 3 followed by 5 + 2 would count as one induction regimen) OR

⁃ Subjects with WHO defined myelodysplastic syndrome with excess blasts-2 (MDS-EB-2) as defined by blast count between 10% - 19% in the bone marrow or peripheral blood blasts 5% - 19% or Auer rods noted and who are refractory or relapsed after at least 4 cycles of a hypomethylating agent (azacitidine, decitabine, or oral decitabine/cedazuridine)

• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix B).

• Participants must have adequate organ and marrow function as defined below:

‣ Estimated Creatinine Clearance ≥30 mL/min by Cockcroft-Gault calculation

⁃ Total Bilirubin ≤1.5 x ULN\*

⁃ ALT and AST ≤3x ULN\*

⁃ EF \>35%: \*unless considered due to leukemic organ involvement. NOTE: Subjects with Gilbert's Syndrome may have a total bilirubin \>1.5 x ULN per discussion with overall study PI.

• WBC \<25,000 / µL on day of 1 of cycle 1; cytoreduction is permitted with hydroxyurea which is allowed throughout cycle 1 until cycle 2 day 1

• Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.

• For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.

• Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.

• Participants with treated central nervous system (CNS) disease are eligible if follow-up brain imaging after CNS-directed therapy shows no evidence of progression

• Male subjects must agree to refrain from unprotected sex and sperm donation from initial drug administration until 90 days after the last dose of study drug.

• Females of childbearing potential (i.e not postmenopausal for at least 1 year or not surgically sterile) must have negative results by a serum pregnancy test performed within 7 days of day 1. Females must agree to refrain from unprotected sex/adequate contraception via barrier method from initial drug administration until 90 days after the last dose of study drug.

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