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

• Status: Not yet recruiting
• Trial end date: 2023-02-01
• Target enrollment: 0
• Participant gender: All

Summary

Pegylated arginine deiminase (ADI-PEG 20) will be combined with venetoclax and azacitidine for treatment of subjects with previously treated or untreated with high risk factor acute myeloid leukemia (AML). Venetoclax and azacitidine are front-line therapy for such patients, and ADI-PEG 20 will be added to this regimen in a phase IA/B study.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Polaris Group
• Treatments: Azacitidine; Venetoclax

Criteria

Inclusion Criteria:

• Lead In and Cohort 1

1. Previously treated AML based on the revised 2017 European LeukemiaNet (ELN) criteria and having ≥10% blasts in bone marrow or peripheral blood

2. Age ≥18 years

• Cohort 2

1. Untreated AML per ELN criteria with high risk features

2. Age ≥ 65 years and ineligible for intensive chemotherapy because of older than 75 years, cardiac disease or prior anthracycline use or high probability of treatment-related mortality

• Life expectancy reasonably adequate for evaluating the treatment

• White blood cell (WBC) count of 10 × 109/L or less. (Use of hydroxyurea to control WBC is allowed till 48 hours prior to protocol treatment)

• Adequate renal function: Creatinine ≤ 1.5 x upper limit of normal (ULN) or creatinine clearance > 40 mL/minute (measured or calculated according to the Cockcroft-Gault formula)

• Adequate liver function

• Total bilirubin ≤ 1.5 x ULN

• ALT and AST both ≤ 2.5 x institutional ULN or ≤ 5 times the ULN for patients with leukemic involvement of liver

Exclusion Criteria:

• Prior treatment for antecedent hematological disorders with hypomethylating agent (more than 2 cycles, those with exposure to <2 cycles will be allowed), venetoclax, or chemotherapy for antecedent hematologic disorders (treatment with other agents including hydroxyurea for myelodysplastic syndrome or myeloproliferative neoplasm is permitted)

• Favorable risk AML per ELN 2017 criteria

• Known active CNS involvement by leukemia