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

NCT ID: NCT05001828

Last Updated: 2025-11-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-05
• Study Completion Date: 2026-07-31

Brief 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.

Detailed Description

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.

Conditions

Acute Myeloid Leukemia, Adult

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Previously Treated AML

Previously treated AML based on the revised revised 2022 WHO criteria with age at least 18 years.

Group Type: EXPERIMENTAL

ADI-PEG 20

Intervention Type: DRUG

ADI-PEG 20 in combination with venetoclax and azacitidine

Untreated AML With High Risk Features

Untreated AML per 2022 WHO criteria with high-risk features and not a candidate for intensive chemotherapy because of age 60 years or older, age-related comorbidities, cardiac disease, prior anthracycline use, high probability of treatment-related mortality, or otherwise would not benefit from intensive chemotherapy treatment.

Group Type: EXPERIMENTAL

ADI-PEG 20

Intervention Type: DRUG

ADI-PEG 20 in combination with venetoclax and azacitidine

Interventions

ADI-PEG 20

ADI-PEG 20 in combination with venetoclax and azacitidine

Intervention Type: DRUG

Other Intervention Names

Venetoclax; Azacitidine

Eligibility Criteria

Inclusion Criteria

• Cohort 1: Previously treated (relapsed/recurrent) or refractory AML based on the 2022 revision to the World Health Organization (WHO) criteria (Arber 2022)
• Cohort 2: Untreated AML per 2022 WHO (Arber 2022) criteria with high-risk features and not a candidate for intensive chemotherapy because of age 60 years or older, age-related comorbidities, cardiac disease, prior anthracycline use, high probability of treatment-related mortality, or otherwise would not benefit from intensive chemotherapy treatment.
• Age ≥ 18 years
• 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 treatments as follows:

1. Cohort 1: >2 cycles of prior combination treatment with venetoclax+hypomethelating agent (i.e. azacitidine, decitabine) is exclusionary. All other prior treatment for antecedent hematological disorders and/or for AML is permitted.

2. Cohort 2: Prior treatment for antecedent hematological disorders with venetoclax or chemotherapy or any prior treatment for their AML is exclusionary. However, treatment with other agents, including hydroxyurea or ≤2 cycles of hypomethylating agent (i.e. azacitidine, decitabine), for MDS or myeloproliferative neoplasm is permitted.

• Cohort 2: Favorable risk AML per European LeukemiaNet (ELN) 2022 criteria (Döhner 2022)
• Known active CNS involvement by leukemia

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Polaris Group

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John S Bomalaski, MD

Role: STUDY_DIRECTOR

Polaris Group

Locations

Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Levine Cancer Institute

Charlotte, North Carolina, United States

MD Anderson Cancer Center

Houston, Texas, United States

Countries

United States

Other Identifiers

POLARIS2020-002

Identifier Type: -

Identifier Source: org_study_id