Phase 1/1b Trial Of Olutasidenib And Ziftomenib For NPM1 And IDH1 Co-Mutated Acute Myeloid Leukemia

Inclusion criteria

• ✓. Age \> 18 years
• ✓. Diagnosis of relapsed or refractory AML (including biphenotypic or bilineage leukemia) as defined by ≥ 5% marrow blasts; patients with isolated extramedullary AML without marrow involvement are not eligible
• ✓. AML disease must be characterized by IDH1 and NPM1 co-mutations as determined by local molecular testing (next generation sequencing, PCR)
• ✓. Eastern Cooperative Oncology Group (ECOG) Performance Status \</=2
• ✓. Adequate renal function with CrCl ≥30 ml/min to be calculated using Cockroft Gault formula
• ✓. Adequate hepatic function (total bilirubin \< 3.0x upper limit of normal (ULN) unless increase is due to Gilbert's disease or leukemic involvement, and AST and/or ALT \< 3x ULN unless considered due to leukemic involvement, in which case total bilirubin \< 5x ULN or AST and/or ALT \< 5x ULN will be considered eligible
• ✓. Baseline QTcF ≤ 480 msec
• ✓. In the absence of rapidly proliferative disease, the interval from prior treatment to time of initiation of study therapy will be 14 days from last cytotoxic or non-cytotoxic (immunotherapy agent(s), or an interval of 5 half- lives of the prior therapy whichever is shorter. Cytarabine (up to 2 gm/m2), leukapheresis, and oral hydroxyurea are permitted in patients with rapidly proliferative disease before the start of study therapy for clinical benefit as needed. Hydroxyurea can also be administered during cycles 1-2 of study therapy for cytoreduction as deemed necessary by the treating physician 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.

Exclusion criteria