What is the mechanism of action of this treatment?

Common treatments for Acute Myeloid Leukemia (AML) include hypomethylating agents like azacitidine and decitabine, which work by inhibiting DNA methylation, leading to the reactivation of tumor suppressor genes and induction of cancer cell death. Venetoclax, a BCL-2 inhibitor, promotes apoptosis in AML cells by disrupting their survival mechanisms. Pegylated arginine deiminase (ADI-PEG 20) depletes arginine, an amino acid essential for the growth of certain cancer cells, thereby inhibiting their proliferation. These treatments are crucial for AML patients as they target specific vulnerabilities in cancer cells, offering potential for improved outcomes and personalized therapy options.

What side effects are associated with this type of intervention?

Common treatments for Acute Myeloid Leukemia (AML) include venetoclax, azacitidine, and pegylated arginine deiminase (ADI-PEG 20). Venetoclax and azacitidine are known to cause side effects such as neutropenia, thrombocytopenia, anemia, gastrointestinal disturbances (nausea, vomiting, diarrhea), and fatigue. ADI-PEG 20, which depletes arginine, may lead to side effects like hepatotoxicity, fatigue, and injection site reactions. General side effects of AML treatments can also include infections due to immunosuppression, mucositis, and organ toxicity.

What prior FDA approvals exist?

FDA-approved treatments for Acute Myeloid Leukemia (AML) include hypomethylating agents (HMAs) such as azacitidine and decitabine, which are often used in combination with other drugs like venetoclax, a BCL2 inhibitor. Venetoclax combined with azacitidine or decitabine has shown efficacy in elderly patients or those unfit for intensive chemotherapy. Another notable drug is ivosidenib, an IDH1 inhibitor, used for patients with specific genetic mutations. While there is no direct mention of FDA-approved drugs that deplete arginine like ADI-PEG 20, the combination of venetoclax and azacitidine represents a similar approach in targeting metabolic pathways to inhibit cancer cell growth.

What other types of research exist?

Promising novel alternatives to Pegylated arginine deiminase (ADI-PEG 20) for Acute Myeloid Leukemia patients include: 1) Hypomethylating agents (HMAs) combined with venetoclax or ivosidenib, 2) Azacitidine plus gilteritinib, and 3) Low-dose cytarabine (LoDAC) combined with venetoclax or glasdegib.

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Enzyme

ADI-PEG 20 + Venetoclax + Azacitidine for Acute Myeloid Leukemia

Phase 1

Recruiting

Research Sponsored by Polaris Group

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Lead In and Cohort 1: Previously treated AML based on the revised 2017 European LeukemiaNet (ELN) criteria and having ≥10% blasts in bone marrow or peripheral blood; Age ≥18 years

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Awards & highlights

Study Summary

This trial will study the addition of ADI-PEG 20 to venetoclax and azacitidine in patients with high-risk AML.

Who is the study for?

This trial is for adults with high-risk Acute Myeloid Leukemia (AML). It's specifically for those aged 65 or older who can't have intensive chemotherapy due to age, heart disease, previous treatments, or risk of treatment-related death. Participants need a reasonable life expectancy and controlled white blood cell count. They must also have adequate kidney and liver function but cannot join if they've had certain prior AML treatments or have leukemia in the brain/spinal cord.Check my eligibility

What is being tested?

The study tests ADI-PEG 20 combined with venetoclax and azacitidine in patients with AML. Venetoclax and azacitidine are standard first-line therapies; this trial adds ADI-PEG 20 to see if it improves outcomes. The study has two parts: one for previously treated patients (Phase IA) and another for untreated elderly patients at high risk (Phase IB).See study design

What are the potential side effects?

Possible side effects include reactions related to immune system activation such as fever or chills, digestive issues like nausea or constipation, potential impact on blood cells leading to increased infection risk or bleeding problems, fatigue, liver function changes, and kidney-related effects.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I am over 18 and have AML with more than 10% blasts in my blood or bone marrow.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 years for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

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

Secondary outcome measures

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

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

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

+1 more

Trial Design

2Treatment groups

Experimental Treatment

Group I: Untreated AML With High Risk FeaturesExperimental Treatment1 Intervention

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

Group II: Previously Treated AMLExperimental Treatment1 Intervention

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

ADI-PEG 20

2013

Completed Phase 2

~190

0 / 1Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Acute Myeloid Leukemia (AML) include hypomethylating agents like azacitidine and decitabine, which work by inhibiting DNA methylation, leading to the reactivation of tumor suppressor genes and induction of cancer cell death. Venetoclax, a BCL-2 inhibitor, promotes apoptosis in AML cells by disrupting their survival mechanisms. Pegylated arginine deiminase (ADI-PEG 20) depletes arginine, an amino acid essential for the growth of certain cancer cells, thereby inhibiting their proliferation. These treatments are crucial for AML patients as they target specific vulnerabilities in cancer cells, offering potential for improved outcomes and personalized therapy options.

Targeting the metabolic vulnerability of acute myeloid leukemia blasts with a combination of venetoclax and 8-chloro-adenosine.A Phase II Study of Arginine Deiminase (ADI-PEG20) in Relapsed/Refractory or Poor-Risk Acute Myeloid Leukemia Patients.Molecular targeting in acute myeloid leukemia.