Phase 1b/2 Study of Decitabine and Venetoclax in Combination With the Targeted Mutant IDH1 Inhibitor Olutasidenib

Exclusion Criteria

• •1. Severe cardiac disorder (eg, congestive heart failure requiring treatment, ejection fraction ≤50%, or chronic stable angina).
• •2. Severe pulmonary disorder (eg, DLCO ≤65% or forced expiratory volume in 1 second \[FEV1\] ≤65%).
• •3. Creatinine clearance ≥30 mL/min to \<45 mL/min.
• •4. Moderate hepatic impairment with total bilirubin \>1.5 to .3.0 x upper limit of normal (ULN)
• •5. ECOG performance status of 2 or 3
• •6. Any other comorbidity that per the investigator renders a patient inappropriate for intensive chemotherapy
• •9. In the absence of rapidly proliferative disease, the interval from prior treatment to time of initiation will be at least 14 days for cytotoxic or non-cytotoxic (immunotherapy agent(s), or an interval of 5 half-lives of the prior therapy. Oral hydroxyurea and/or cytarabine (up to 2 g/m2) for patients with rapidly proliferative disease is allowed before the start of study therapy, as needed, for clinical benefit and after discussion with the PI. Concurrent intrathecal therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted.
• •10. Male participants who are sexually active with a women of childbearing potential (WOCBP) and who have not had vasectomies must be willing to use a barrier method of contraception and refrain from sperm donation from initial study drug until 90 days after last dose of study drug.
• •11. Willing and able to provide informed consent.
• •1. Participants with t(15;17) karyotypic abnormality or acute promyelocytic leukemia (French-American-British \[FAB\] class M3-AML).
• •2. Participants with any concurrent uncontrolled clinically significant medical condition including life-threatening severe infection, or psychiatric illness, which could place the participants at unacceptable risk of study treatment.
• •3. Participants with active, uncontrolled leukemia involvement of the CNS
• •4. Participants with active graft-versus-host-disease (GVHD) status post stem cell transplant including active cGVHD requiring topic therapy. Patients must have discontinued calcineurin inhibitors at least 4 weeks prior to start of study treatment.
• •5. Participants with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications.
• •6. Known active hepatitis B (HBV) or Hepatitis C (HCV) infection or known HIV infection.
• •7. Participant has a white blood cell count \> 25 x 10\^9/L. (Note: Hydroxyurea and cytarabine is permitted to meet this criterion.)
• •8. Nursing women, women of childbearing potential (WOCBP) with positive urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception.
• •A) Appropriate highly effective method(s) of contraception include oral or injectable hormonal birth control, IUD, and double barrier methods (for example a condom in combination with a spermicide).