Study of ADI-PEG 20, Venetoclax and Azacitidine in Acute Myeloid Leukemia

This is an open label, single arm, phase 1 trial with recommended phase 2 dose (RP2D) cohorts based on subject inclusion criteria. Lead In: 6 patients will be enrolled to be treated with standard dose of azacitidine and venetoclax and the expected RP2D of ADI-PEG 20 (dose level 0). In case of DLT occurring in \>1 patient in cycle 1, 6 additional patients will be accrued at dose level -1 of ADI-PEG 20 while keeping the doses of azacitidine and venetoclax unchanged (Dose level -1). Enrollment to cohort 1 and 2 will start after ≤1 patient out of 6 encounters DLT in cycle 1 at one of these dose levels. The 6 patients enrolled at that dose level will be counted for efficacy analysis. Cohort 1: Relapsed or refractory AML: target response 25%. Historical expectation for venetoclax and azacitidine is 15%. Cohort 2: Newly diagnosed high risk AML: Target response 55%. Historical expectation for venetoclax and azacitidine is 40%. Treatment may be continued for a maximum of 24 cycles or 104 doses of ADI-PEG 20 (study Week 103), whichever is reached first.