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

NCT03173248 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 1 other identifier: AG120-C-009
• Study Type: interventional
• Target: 146
• Locations: 19 countries
• Sites: 88

Brief Summary

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.

Conditions

Newly Diagnosed Acute Myeloid Leukemia (AML); Untreated AML; AML Arising From Myelodysplastic Syndrome (MDS); Leukemia, Myeloid, Acute

Keywords

Acute Myeloid Leukemia; Leukemia; Azacitidine; AG-120; ivosidenib

Outcome Measures

Primary Outcomes (1)

• Event-Free Survival (EFS)

  EFS was defined as the time from randomization until treatment failure, relapse from remission, or death from any cause, whichever occurs first. Treatment failure was defined as failure to achieve complete remission (CR) by Week 24. CR: Bone marrow blasts \<5% and no Auer rods; absence of extramedullary disease; Absolute neutrophil count (ANC) ≥1.0 × 10\^9 per litre (10\^9/L) (1000 per microlitre \[1000/μL\]); platelet count ≥100 × 10\^9/L (100,000/μL); independence of red blood cell transfusions. Participants who had an EFS event (relapse or death) after, 2 or more missing disease assessments were censored at the last adequate disease assessment documenting no relapse before the missing assessments. The reported data represents the Kaplan-Meier median value.

  Up to Week 24

Secondary Outcomes (32)

• Complete Remission Rate (CR Rate)

  Up to approximately 52 months

• Overall Survival (OS)

  Up to approximately 52 months

• CR + Complete Remission With Partial Hematologic (CRh) Rate

  Up to approximately 52 months

• Objective Response Rate (ORR)

  Up to approximately 52 months

• CR + CRi (Including CRp) Rate

  Up to approximately 52 months

Study Arms (2)

AG-120 + Azacitidine

EXPERIMENTAL

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.

Drug: AG-120; Drug: Azacitidine

Placebo + Azacitidine

PLACEBO COMPARATOR

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 .

Drug: Placebo; Drug: Azacitidine

Interventions

AG-120 DRUG

Tablets administered orally

Also known as: Ivosidenib

AG-120 + Azacitidine

Placebo DRUG

Tablets administered orally

Placebo + Azacitidine

Azacitidine DRUG

Administered SC or IV

Also known as: Vidaza®

AG-120 + Azacitidine; Placebo + Azacitidine

Eligibility Criteria

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

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.

Sponsors & Collaborators

• Institut de Recherches Internationales Servier: lead

Study Sites (90)

Norton Cancer Institute - Suburban

Louisville, Kentucky, 40207, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

Location

Salzburger Landeskliniken

Salzburg, 5020, Austria

Location

Krankenhaus Hietzing mit Neurologischem Zentrum Rosenhugel

Vienna, 1130, Austria

Location

Unicamp Universidade Estadual de Campinas

Campinas, São Paulo, 13083-878, Brazil

Location

Hospital Amaral Carvalho

Jaú, São Paulo, 17210-120, Brazil

Location

Instituto Nacional de Cancer

Rio de Janeiro, 20230-130, Brazil

Location

Hospital Sirio Libanes

São Paulo, 01308-050, Brazil

Location

Hospital Sao Jose

São Paulo, 01321-001, Brazil

Location

Hospital Santa Marcelina

São Paulo, 08270-070, Brazil

Location

Cancer Care Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

Henan Cancer Hospital

Zhengzhou, Henan, 450008, China

Location

West China Hospital Sichuan University

Chengdu, Sichuan, 610041, China

Location

Peking Union Medical College Hospital

Beijing, China

Location

Guangdong Provincial People's Hospital

Guangzhou, 510080, China

Location

The First Affiliated Hospital, College of Medicine, Zhejiang University

Hangzhou, 310003, China

Location

Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences

Tianjin, 300020, China

Location

Fakultni nemocnice Ostrava

Ostrava, Czechia

Location

Hopital Haut Leveque

Pessac, Gironde, 33604, France

Location

Hopital Bretonneau

Tours, Indre-et-Loire, 37044, France

Location

Hotel Dieu - Nantes

Nantes, Loire-Atlantique, 44093, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, Rhone, 69495, France

Location

Centre Hospitalier Le Mans

Le Mans, Sarthe, 72037, France

Location

CHRU de Brest - Hopital Morvan

Brest, 29609, France

Location

Institut dHematologie de Basse Normandie

Caen, 14000, France

Location

CHU de Grenoble

Grenoble, 38043, France

Location

Centre Hospitalier de Versailles CHV Hopital Andre Mignot

Le Chesnay, 78 157, France

Location

Groupe Hospitalier Necker Enfants Malades

Paris, 75015, France

Location

CHRU de Poitiers La Miletrie

Poitiers, 86021, France

Location

Hopital de Hautepierre

Strasbourg, 67200, France

Location

EDOG - Institut Claudius Regaud - PPDS

Toulouse, 31059, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Universitatsklinikum Essen

Essen, North Rhine-Westphalia, 45122, Germany

Location

Klinikum Chemnitz gGmbH

Chemnitz, Saxony, 09113, Germany

Location

Charite - Universitatsmedizin Berlin

Berlin, 13353, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Universitatsklinikum Leipzig

Leipzig, 04103, Germany

Location

LMU Klinikum der Universitat Munchen

München, 81377, Germany

Location

Universitatsklinikum Ulm

Ulm, 89081, Germany

Location

Rabin Medical Center - PPDS

Petah Tikva, 49100, Israel

Location

Kaplan Medical Center

Rehovot, 7610000, Israel

Location

Shamir Medical Center Assaf Harofeh

Tzrifin, 70300, Israel

Location

ASST dei Sette Laghi - Ospedale Di Circolo E Fondazione Macchi

Varese, Lombardy, 21100, Italy

Location

Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST - PPDS

Meldola, 47014, Italy

Location

Ospedale San Raffaele S.r.l. - PPDS

Milan, 20132, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda Ca' Granda

Milan, 20162, Italy

Location

Fondazione IRCCS Policlinico San Matteo di Pavia

Pavia, 27100, Italy

Location

Ospedale Infermi di Rimini

Rimini, 47900, Italy

Location

Azienda Ospedaliera Citta della Salute e della Scienza di Torino

Torino, 10126, Italy

Location

Matsuyama Red Cross Hospital

Matsuyama, Ehime, 790-8524, Japan

Location

University of Fukui Hospital

Fukui, 910-1193, Japan

Location

Japanese Red Cross Society Himeji Hospital

Himeji, 670-8540, Japan

Location

Kobe City Medical Center General Hospital

Kobe, Japan

Location

SINACOR

Culiacán, 80230, Mexico

Location

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

México, 14000, Mexico

Location

VU Medisch Centrum

Amsterdam, North Holland, 1081 HV, Netherlands

Location

Universitair Medisch Centrum Groningen

Nijmegen, 6525 GA, Netherlands

Location

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu

Wroclaw, Lower Silesian Voivodeship, 50-367, Poland

Location

Instytut Hematologii i Transfuzjologii

Warsaw, Masovian Voivodeship, 02-776, Poland

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-214, Poland

Location

Kaluga Regional Clinical Hospital

Kaluga, 248007, Russia

Location

City Clinical Hospital # 40

Moscow, 129301, Russia

Location

National Cancer Center

Goyang-si, Gyeonggido, 10408, South Korea

Location

Ajou University Hospital

Suwon, Gyeonggido, 16499, South Korea

Location

Pusan National University Hospital

Busan, 602-739, South Korea

Location

Severance Hospital Yonsei University Health System

Seoul, 03722, South Korea

Location

Seoul National University Hospital

Seoul, 110-744, South Korea

Location

CHUS H. Clinico U. de Santiago

Santiago de Compostela, A Coruna, 15706, Spain

Location

Hospital Universitario Son Espases

Palma de Mallorca, Balearic Islands, 07010, Spain

Location

Hospital Universitario Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Hospital Universitario de Gran Canaria Doctor Negrin

Las Palmas de Gran Canaria, Las Palmas, 35010, Spain

Location

Hospital Universitario Vall d'Hebron - PPDS

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario Virgen del Rocio - PPDS

Seville, 41013, Spain

Location

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, 46026, Spain

Location

Hospital Clinico Universitario Lozano Blesa

Zaragoza, 50009, Spain

Location

Changhua Christian Medical Foundation Changhua Christian Hospital

Changhua, 500, Taiwan

Location

Kaohsiung Medical University Hospital

Kaohsiung City, 807, Taiwan

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

Chi Mei Medical Center, Liouying

Tainan, 736, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Birmingham Heartlands Hospital

Birmingham, West Midlands, B9 5SS, United Kingdom

Location

Related Publications (3)

• Montesinos P, Recher C, Vives S, Zarzycka E, Wang J, Bertani G, Heuser M, Calado RT, Schuh AC, Yeh SP, Daigle SR, Hui J, Pandya SS, Gianolio DA, de Botton S, Dohner H. Ivosidenib and Azacitidine in IDH1-Mutated Acute Myeloid Leukemia. N Engl J Med. 2022 Apr 21;386(16):1519-1531. doi: 10.1056/NEJMoa2117344.

  PMID: 35443108 BACKGROUND

• Montesinos P, Marchione DM, Recher C, Heuser M, Vives S, Zarzycka E, Wang J, Riva M, Calado RT, Schuh AC, Yeh SP, Tron AE, Hui J, Gianolio DA, Choe S, Patel P, De Botton S, DiNardo CD, Dohner H. Long-term results from the AGILE study of azacitidine plus ivosidenib vs placebo in newly diagnosed IDH1-mutated AML. Blood Adv. 2025 Oct 28;9(20):5177-5189. doi: 10.1182/bloodadvances.2025016399.

  PMID: 40706052 DERIVED

• Woods A, Norsworthy KJ, Wang X, Vallejo J, Chiu Yuen Chow E, Li RJ, Sun J, Charlab R, Jiang X, Pazdur R, Theoret MR, de Claro RA. FDA Approval Summary: Ivosidenib in Combination with Azacitidine for Treatment of Patients with Newly Diagnosed Acute Myeloid Leukemia with an IDH1 Mutation. Clin Cancer Res. 2024 Apr 1;30(7):1226-1231. doi: 10.1158/1078-0432.CCR-23-2234.

  PMID: 38010220 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia

Interventions

ivosidenib; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; 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

Results Point of Contact

• Title: Clinical Studies Department
• Organization: Institut de Recherches Internationales Servier (I.R.I.S.)

scientificinformation@servier.com

+33155726000

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2017
• First Posted: June 1, 2017
• Study Start: June 26, 2017
• Primary Completion: March 18, 2021
• Study Completion (Estimated): June 30, 2026
• Last Updated: November 10, 2025
• Results First Posted: March 23, 2023

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: After Marketing Authorisation in EEA or US if the study is used for the approval.
• Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.

Locations

FR (14); JP (4); ES (13); CA (2); AU (3); IL (3); ME (2); US (2); NL (2); BR (6); DE (7); IT (7); PL (3); KR (5); TW (5); GB (1); RU (2); CN (6); CZ (1)