A Phase 2 Study of Olutasidenib in Combination With Azacitidine Followed by Olutasidenib Maintenance After Venetoclax Plus a Hypomethylating Agent Regimen (HMA-VEN) for IDH1-Mutated Acute Myeloid Leukemia (AML)
This phase II trial studies how well giving olutasidenib with azacitidine, followed by olutasidenib maintenance, works in treating patients with IDH1-mutated acute myeloid leukemia (AML) who have received prior treatment with venetoclax plus a hypomethylating agent (HMA-Ven). Olutasidenib and azacitidine may inhibit the growth of cancer cells by blocking certain enzymes required for cell growth. Maintenance therapy can help prevent or delay cancer from coming back. Olutasidenib with azacitidine followed by olutasidenib maintenance may be effective in treating patients with IDH1-mutated AML who have received prior HMA-Ven.
• Pathologically documented AML (except acute promyelocytic leukemia with the t(15;17) translocation) as defined by the World Health Organization (WHO) or International Consensus Classification criteria
• Achieved complete response (CR)/complete remission with incomplete count recovery (CRi) response to first line HMA-Ven according to the European Leukemia Net (ELN) recommendations for diagnosis as determined by investigator review
• Documented IDH1-R132 mutations (≥ 0.01%) detected in the bone marrow or blood. Mutation must be present at the time of AML diagnosis or after initiating HMA-Ven
• Receiving first-line HMA-Ven with less than or equal to 4 cycles of HMA-Ven at the time of enrollment. Participants must discontinue venetoclax (Ven) at least 1 week (or 5 half-lives, whichever is shorter) from initiating study treatment
• Candidate for standard of care azacitidine
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 50%)
• No prior solid organ allograft
• Recovery from the non-hematologic toxic effects of prior treatment to grade ≤ 1, or baseline value according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) classification (excluding infertility or alopecia)
• Aged ≥ 18 at the time of consent
• Creatinine clearance ≥ 40 mL/min (calculated by the Cockcroft-Gault formula or measured by 24-hour urine collection)
• Serum alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN)
• Serum aspartate aminotransferase (AST) ≤ 3 × ULN
• Bilirubin ≤ 2 x ULN unless due to Gilbert's syndrome or controlled autoimmune hemolytic anemia (not requiring immunosuppressive other than ≤ 20 mg of prednisolone daily)
⁃ Note: Patients with Gilbert's syndrome may be included if total bilirubin is ≤ 3 × ULN and direct bilirubin is ≤ 2 × ULN
• Prothrombin time (PT) or international normalized ratio (INR)/activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN
• Women of child-bearing potential, men, and their respective partners, must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days after the last dose of olutasidenib
• Must sign and date the informed consent form prior to undergoing any study procedures