Study of AG-120 (Ivosidenib) vs. Placebo in Combination With Azacitidine in Participants With Previously Untreated Acute Myeloid Leukemia With an IDH1 Mutation

Running, not enrolling · Phase 3 · Has a placebo group

Conditions studied: Newly Diagnosed Acute Myeloid Leukemia (AML), Untreated AML, AML Arising From Myelodysplastic Syndrome (MDS), Leukemia, Myeloid, Acute

In brief

Study AG120-C-009 is a global, Phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial to evaluate the efficacy and safety of AG-120 (ivosidenib) + azacitidine vs placebo + azacitidine in adult participants with previously untreated IDH1m AML who are considered appropriate candidates for non-intensive therapy. The primary endpoint is event-free survival (EFS). The key secondary efficacy endpoints are overall survival (OS), rate of complete remission (CR), rate of CR and complete remission with partial hematologic recovery (CRh), and overall response rate (ORR). Participants eligible for study treatment based on Screening assessments will be randomized 1:1 to receive oral AG-120 or matched placebo, both administered in combination with subcutaneous (SC) or intravenous (IV) azacitidine. An estimated 200 participants will take part in the study.

Key facts

Study ID

NCT03173248

Run by

Institut de Recherches Internationales Servier

People needed

146

Starts

2017-06-26

Expected to finish

2026-06-30

Last updated by the study team

2026-06-29

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Be ≥ 18 years of age and meet at least 1 of the following criteria defining ineligibility for intensive induction chemotherapy (IC): ≥ 75 years old, Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 2, severe cardiac disorder (e.g., congestive heart failure requiring treatment, left ventricular ejection fraction (LVEF), ≤50%, or chronic stable angina), severe pulmonary disorder (e.g., diffusing capacity of the lungs for carbon monoxide ≤65% or forced expiratory volume in 1 second ≤65%), creatinine clearance <45 mL/minute, bilirubin >1.5 times the upper limit of normal (ULN) and/or have any other comorbidity that the Investigator judges to be incompatible with intensive IC and must be reviewed and approved by the Medical Monitor before study enrollment.
• Have previously untreated AML, defined according to World Health Organization (WHO) criteria, with ≥ 20% leukemic blasts in the bone marrow. Participants with extramedullary disease alone (i.e., no detectable bone marrow and no detectable peripheral blood AML) are not eligible for the study.
• Have an isocitrate dehydrogenase 1 (IDH1) mutation.
• Have an ECOG PS score of 0 to 2.
• Have adequate hepatic function.
• Have adequate renal function.
• Have agreed to undergo serial blood and bone marrow sampling.
• Be able to understand and willing to sign an informed consent form (ICF).
• Be willing to complete Quality of Life assessments during the study
• If female with reproductive potential, must have a negative serum pregnancy test prior to the start of study therapy. Females of reproductive potential, as well as fertile men and their female partners of reproductive potential, must agree to use 2 effective forms of contraception.

You may not qualify if…

• Are candidates for and willing to receive intensive induction chemotherapy (IC) for their AML.
• Have received any prior treatment for AML with the exception of hydroxyurea.
• Have received a hypomethylating agent for myelodysplastic syndrome (MDS).
• Participants who had previously received an experimental agent for MDS may not be randomized until a washout period has elapsed since the last dose of that agent.
• Have received prior treatment with an IDH1 inhibitor.
• Have a known hypersensitivity to any of the components of AG-120, matched placebo, or azacitidine.
• Are female and pregnant or breastfeeding.
• Have an active, uncontrolled, systemic fungal, bacterial, or viral infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment.
• Have a prior history of cancer other than MDS or myeloproliferative disorder, unless the participant has been free of the disease for ≥ 1 year prior to the start of study treatment.
• Have had significant active cardiac disease within 6 months prior to the start of the study treatment.
• Have any condition that increases the risk of abnormal ECG or cardiac arrhythmia.
• Have a condition that limits the ingestion or absorption of drugs administered by mouth.
• Have uncontrolled hypertension (systolic blood pressure [BP] > 180 mmHg or diastolic BP > 100 mmHg).
• Have clinical symptoms suggestive of active central nervous system (CNS) leukemia or known CNS leukemia.
• Have immediate, life-threatening, severe complications of leukemia, such as uncontrolled bleeding, pneumonia with hypoxia or sepsis, and/or disseminated intravascular coagulation.
• Have any other medical or psychological condition deemed by the Investigator to be likely to interfere with the participant's ability to give informed consent or participate in the study.
• Are taking medications that are known to prolong the QT interval unless they can be transferred to other medications within ≥5 half-lives prior to dosing, or unless the medications can be properly monitored during the study. (If equivalent medication is not available, heart rate corrected QT interval [QTc] will be closely monitored.)
• Have a known medical history of progressive multifocal leukoencephalopathy.

Where it is running

• Massachusetts General Hospital — Boston, Massachusetts, United States
• Royal Prince Alfred Hospital — Camperdown, New South Wales, Australia
• Royal Adelaide Hospital — Adelaide, South Australia, Australia
• Flinders Medical Centre — Bedford Park, South Australia, Australia
• Salzburger Landeskliniken — Salzburg, Austria
• Krankenhaus Hietzing mit Neurologischem Zentrum Rosenhugel — Vienna, Austria
• Unicamp Universidade Estadual de Campinas — Campinas, São Paulo, Brazil
• Hospital Amaral Carvalho — Jaú, São Paulo, Brazil
• Instituto Nacional de Cancer — Rio de Janeiro, Brazil
• Hospital Sirio Libanes — São Paulo, Brazil
• Hospital Sao Jose — São Paulo, Brazil
• Hospital Santa Marcelina — São Paulo, Brazil
• Cancer Care Manitoba — Winnipeg, Manitoba, Canada
• University Health Network — Toronto, Ontario, Canada
• Henan Cancer Hospital — Zhengzhou, Henan, China
• West China Hospital Sichuan University — Chengdu, Sichuan, China
• Peking Union Medical College Hospital — Beijing, China
• Guangdong Provincial People's Hospital — Guangzhou, China
• The First Affiliated Hospital, College of Medicine, Zhejiang University — Hangzhou, China
• Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences — Tianjin, China
• Fakultni nemocnice Ostrava — Ostrava, Czechia
• Hopital Haut Leveque — Pessac, Gironde, France
• Hopital Bretonneau — Tours, Indre-et-Loire, France
• Hotel Dieu - Nantes — Nantes, Loire-Atlantique, France
• Norton Cancer Institute - Suburban — Louisville, Kentucky, United States

Full record on ClinicalTrials.gov

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