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

Sponsor
Polaris Group (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT05001828
Collaborator
(none)
60
1
2
44
1.4

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: ADI-PEG 20
Phase 1

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 in Cohort 1. 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 total of 24 cycles, each of 28 days.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
60 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase IA/B Combination Study of ADI-PEG 20, Venetoclax and Azacitidine in Patients With Acute Myeloid Leukemia (AML)
Anticipated Study Start Date :
Apr 1, 2022
Anticipated Primary Completion Date :
Jul 1, 2025
Anticipated Study Completion Date :
Dec 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Previously Treated AML

Previously treated AML based on the revised 2017 European LeukemiaNet (ELN) criteria with age at least 18 years, and having ≥10% blasts in bone marrow or peripheral blood

Drug: ADI-PEG 20
ADI-PEG 20 in combination with venetoclax and azacitidine
Other Names:
  • Venetoclax
  • Azacitidine
  • Experimental: Untreated AML With High Risk Features

    Untreated AML per ELN criteria with high risk features, or 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

    Drug: ADI-PEG 20
    ADI-PEG 20 in combination with venetoclax and azacitidine
    Other Names:
  • Venetoclax
  • Azacitidine
  • Outcome Measures

    Primary Outcome Measures

    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 Outcome Measures

    1. Determine preliminary evidence of tumor activity, per the revised 2017 European LeukemiaNet criteria [2 years]

    2. Determine the peripheral blood arginine levels of ADI-PEG 20 in combination with venetoclax and azacitidine [2 years]

    3. Determine the peripheral blood citrulline levels of ADI-PEG 20 in combination with venetoclax and azacitidine [2 years]

    4. Determine the anti-drug antibodies of ADI-PEG 20 in combination with venetoclax and azacitidine [2 years]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 99 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 MD Anderson Cancer Center Houston Texas United States 77030

    Sponsors and Collaborators

    • Polaris Group

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Polaris Group
    ClinicalTrials.gov Identifier:
    NCT05001828
    Other Study ID Numbers:
    • POLARIS2020-002
    First Posted:
    Aug 12, 2021
    Last Update Posted:
    Apr 20, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Apr 20, 2022