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

NCT05001828 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: POLARIS2020-002
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 3

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.

Conditions

Acute Myeloid Leukemia, Adult

Outcome Measures

Primary Outcomes (1)

• Determine the RP2D of ADI-PEG 20 in combination with venetoclax and azacitidine, per the number of subjects with treatment-related adverse events by current CTCAE

  6 months

Secondary Outcomes (4)

• Determine preliminary evidence of tumor activity, per the revised 2017 European LeukemiaNet criteria

  2 years

• Determine the peripheral blood arginine levels of ADI-PEG 20 in combination with venetoclax and azacitidine

  2 years

• Determine the peripheral blood citrulline levels of ADI-PEG 20 in combination with venetoclax and azacitidine

  2 years

• Determine the anti-drug antibodies of ADI-PEG 20 in combination with venetoclax and azacitidine

  2 years

Study Arms (2)

Previously Treated AML

EXPERIMENTAL

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

Drug: ADI-PEG 20

Untreated AML With High Risk Features

EXPERIMENTAL

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.

Drug: ADI-PEG 20

Interventions

ADI-PEG 20 DRUG

ADI-PEG 20 in combination with venetoclax and azacitidine

Also known as: Venetoclax, Azacitidine

Previously Treated AML; Untreated AML With High Risk Features

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Polaris Group: lead

Study Sites (3)

Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

ADI PEG20; venetoclax; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• John S Bomalaski, MD

  Polaris Group

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2021
• First Posted: August 12, 2021
• Study Start: April 5, 2022
• Primary Completion: May 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 21, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)