What side effects are associated with this type of intervention?

Common treatments for Acute Myeloid Leukemia (AML) include hypomethylating agents (HMAs) like azacitidine, often combined with targeted agents such as ivosidenib. Known side effects of azacitidine include hematologic toxicities like neutropenia, thrombocytopenia, and anemia, as well as gastrointestinal symptoms such as nausea, vomiting, and diarrhea. Ivosidenib, which targets the IDH1 mutation, can cause differentiation syndrome, leukocytosis, and QT prolongation. Other common AML treatments, such as cytarabine and daunorubicin, are associated with myelosuppression, mucositis, and cardiotoxicity. Patients should discuss these potential side effects with their healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for Acute Myeloid Leukemia (AML), including hypomethylating agents (HMAs) like azacitidine and decitabine, which are often used in combination with other drugs. Ivosidenib, an IDH1 inhibitor, is specifically approved for AML patients with an IDH1 mutation. Another similar drug is enasidenib, which targets the IDH2 mutation. These targeted therapies are part of a broader strategy to treat AML by inhibiting specific genetic mutations that drive the disease.

What other types of research exist?

Promising novel alternatives to AG-120 (ivosidenib) for AML patients include: 1) Venetoclax combined with low-dose cytarabine (LoDAC), which has shown superior outcomes compared to LoDAC monotherapy. 2) HMA (hypomethylating agents) such as decitabine or azacitidine combined with venetoclax, which are effective for initial treatment of AML. These combinations are particularly suitable for patients who are not candidates for intensive treatment.

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IDH1 Inhibitor

Ivosidenib + Azacitidine for Acute Myeloid Leukemia (AGILE Trial)

Phase 3

Waitlist Available

Research Sponsored by Institut de Recherches Internationales Servier

Eligibility Criteria Checklist

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

Must have

Be ≥ 18 years of age

Have previously untreated AML with ≥ 20% leukemic blasts in the bone marrow

Must not have

Have received a hypomethylating agent for myelodysplastic syndrome (MDS)

Are candidates for and willing to receive intensive induction chemotherapy (IC) for their AML

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 52 months

Awards & highlights

Pivotal Trial

Summary

This trial is testing a new oral drug, ivosidenib, combined with an injectable drug, azacitidine. It targets adults with a specific type of untreated leukemia who can't undergo intensive treatments. Ivosidenib blocks a faulty enzyme in cancer cells, and azacitidine stops these cells from growing.

Who is the study for?

This trial is for adults with previously untreated Acute Myeloid Leukemia (AML) who have an IDH1 mutation and are not suitable for intensive chemotherapy. They must have good liver and kidney function, agree to regular blood and bone marrow tests, understand the study, consent to it, and if of childbearing potential, use two forms of contraception.

What is being tested?

The trial is testing AG-120 (Ivosidenib) combined with Azacitidine against a placebo plus Azacitidine in patients with AML. It's a global Phase 3 study where participants are randomly assigned to either treatment group. The main goal is to see how long patients live without their disease getting worse.

What are the potential side effects?

Possible side effects include issues affecting the heart rhythm or electrical activity (QT interval changes), allergic reactions to medication components, infection risks due to weakened immune system from leukemia or its treatments, as well as general drug-related side effects like nausea or fatigue.

Eligibility Criteria

Inclusion Criteria

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

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I am 18 years old or older.

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My leukemia has not been treated and my bone marrow shows a high number of cancer cells.

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My cancer has an IDH1 mutation.

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I can take care of myself and am up and about more than half of the day.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been treated with a drug to modify my DNA for MDS.

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I am willing and able to undergo strong chemotherapy for my AML.

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I have been treated with an IDH1 inhibitor before.

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I am currently pregnant or breastfeeding.

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I have trouble swallowing or absorbing pills.

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I have symptoms or a diagnosis of leukemia in my brain or spinal cord.

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I am experiencing severe, life-threatening complications from leukemia.

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I have been diagnosed with progressive multifocal leukoencephalopathy.

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I have an ongoing infection that hasn't improved with treatment.

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I have a condition that could affect my heart's rhythm.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 52 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 52 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 52 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Event-Free Survival (EFS)

Secondary study objectives

CR + CRi (Including CRp) Rate

CR + Complete Remission With Partial Hematologic (CRh) Rate

Change From Baseline in the EORTC EQ-5D-5L Questionnaire

+25 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: AG-120 + AzacitidineExperimental Treatment2 Interventions

Participants received AG-120 500 mg orally, once daily (QD) in combination with azacitidine 75 milligrams per square meter per day (mg/m\^2/day) subcutaneously (SC) or intravenously (IV), on Days 1-7, or on Days 1-5 and 8-9, of each 28-day cycle for a minimum of 6 cycles until death, disease relapse, disease progression, development of unacceptable toxicity (adverse event), confirmed pregnancy, withdrawal by participant or protocol violation.

Group II: Placebo + AzacitidinePlacebo Group2 Interventions

Participants received AG-120 matching placebo orally, QD in combination with azacitidine 75 mg/m\^2/day SC or IV, on Days 1-7, or on Days 1-5 and 8-9, of each 28-day cycle for a minimum of 6 cycles until death, disease relapse, disease progression, development of unacceptable toxicity (adverse event), confirmed pregnancy, withdrawal by participant or protocol violation .

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

AG-120

2017

Completed Phase 3

~370

Azacitidine

2012

Completed Phase 3

~1440

0 / 14Eligibility 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

The most common treatments for Acute Myeloid Leukemia (AML) include targeted therapies, hypomethylating agents, and traditional chemotherapy. Ivosidenib, a targeted therapy, inhibits the mutant IDH1 enzyme, which is crucial in halting the production of the oncometabolite 2-hydroxyglutarate, thereby restoring normal cell differentiation. Hypomethylating agents like azacitidine and decitabine work by incorporating into DNA and inhibiting DNA methyltransferase, leading to reactivation of tumor suppressor genes. Traditional chemotherapy, such as cytarabine and daunorubicin, targets rapidly dividing cells by interfering with DNA synthesis and function. These treatments are vital for AML patients as they address the underlying genetic and cellular abnormalities, aiming to induce remission and improve survival rates.

The Molecular Mechanisms of Resistance to IDH Inhibitors in Acute Myeloid Leukemia.New drugs approved for acute myeloid leukaemia in 2018.Molecular targeting in acute myeloid leukemia.