Newly Diagnosed Acute Myeloid Leukemia (AML)Phase 3AGILENCT03173248
Study of AG-120 (Ivosidenib) vs. Placebo in Combination With Azacitidine in Participants With Previously Untreated Acute Myeloid Leukemia With an IDH1 Mutation
A Phase 3 study testing AG-120 and Azacitidine in people with Newly Diagnosed Acute Myeloid Leukemia (AML) and Untreated AML, run by Institut de Recherches Internationales Servier at 90 sites in 20 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Newly Diagnosed Acute Myeloid Leukemia (AML), Untreated AML, AML Arising From Myelodysplastic Syndrome (MDS)
- What is being tested?
- AG-120 and Azacitidine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 146 participants
- Where
- 90 sitesin 20 countries
- Study dates
- 26 Jun 2017to 30 Jun 2026
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
90 sites in 20 countries.
90 sites in 20 countries
France14 sites
CHRU de Brest - Hopital Morvan
Brest, 29609
Institut dHematologie de Basse Normandie
Caen, 14000
CHU de Grenoble
Grenoble, 38043
Centre Hospitalier de Versailles CHV Hopital Andre Mignot
Le Chesnay, 78 157
Centre Hospitalier Le Mans
Le Mans, Sarthe, 72037
Hotel Dieu - Nantes
Nantes, Loire-Atlantique, 44093
Groupe Hospitalier Necker Enfants Malades
Paris, 75015
Hopital Haut Leveque
Pessac, Gironde, 33604
Centre Hospitalier Lyon Sud
Pierre-Bénite, Rhone, 69495
CHRU de Poitiers La Miletrie
Poitiers, 86021
Hopital de Hautepierre
Strasbourg, 67200
EDOG - Institut Claudius Regaud - PPDS
Toulouse, 31059
Hopital Bretonneau
Tours, Indre-et-Loire, 37044
Institut Gustave Roussy
Villejuif, 94805
Spain13 sites
Hospital Universitario Germans Trias i Pujol
Badalona, Barcelona, 08916
Hospital Universitario Vall d'Hebron - PPDS
Barcelona, 08035
Hospital Clinic de Barcelona
Barcelona, 08036
Hospital Universitario de Gran Canaria Doctor Negrin
Las Palmas de Gran Canaria, Las Palmas, 35010
Hospital General Universitario Gregorio Maranon
Madrid, 28007
Hospital Universitario Ramon y Cajal
Madrid, 28034
Hospital Universitario Fundacion Jimenez Diaz
Madrid, 28040
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Universitario Son Espases
Palma de Mallorca, Balearic Islands, 07010
CHUS H. Clinico U. de Santiago
Santiago de Compostela, A Coruna, 15706
Hospital Universitario Virgen del Rocio - PPDS
Seville, 41013
Hospital Universitari i Politecnic La Fe de Valencia
Valencia, 46026
Hospital Clinico Universitario Lozano Blesa
Zaragoza, 50009
Germany7 sites
Charite - Universitatsmedizin Berlin
Berlin, 13353
Klinikum Chemnitz gGmbH
Chemnitz, Saxony, 09113
Universitatsklinikum Essen
Essen, North Rhine-Westphalia, 45122
Medizinische Hochschule Hannover
Hanover, 30625
Universitatsklinikum Leipzig
Leipzig, 04103
LMU Klinikum der Universitat Munchen
München, 81377
Universitatsklinikum Ulm
Ulm, 89081
Italy7 sites
Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST - PPDS
Meldola, 47014
Ospedale San Raffaele S.r.l. - PPDS
Milan, 20132
ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda Ca' Granda
Milan, 20162
Fondazione IRCCS Policlinico San Matteo di Pavia
Pavia, 27100
Ospedale Infermi di Rimini
Rimini, 47900
Azienda Ospedaliera Citta della Salute e della Scienza di Torino
Torino, 10126
ASST dei Sette Laghi - Ospedale Di Circolo E Fondazione Macchi
Varese, Lombardy, 21100
Brazil6 sites
Unicamp Universidade Estadual de Campinas
Campinas, São Paulo, 13083-878
Hospital Amaral Carvalho
Jaú, São Paulo, 17210-120
Instituto Nacional de Cancer
Rio de Janeiro, 20230-130
Hospital Sirio Libanes
São Paulo, 01308-050
Hospital Sao Jose
São Paulo, 01321-001
Hospital Santa Marcelina
São Paulo, 08270-070
China6 sites
Peking Union Medical College Hospital
Beijing
West China Hospital Sichuan University
Chengdu, Sichuan, 610041
Guangdong Provincial People's Hospital
Guangzhou, 510080
The First Affiliated Hospital, College of Medicine, Zhejiang University
Hangzhou, 310003
Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences
Tianjin, 300020
Henan Cancer Hospital
Zhengzhou, Henan, 450008
South Korea5 sites
Pusan National University Hospital
Busan, 602-739
National Cancer Center
Goyang-si, Gyeonggido, 10408
Severance Hospital Yonsei University Health System
Seoul, 03722
Seoul National University Hospital
Seoul, 110-744
Ajou University Hospital
Suwon, Gyeonggido, 16499
Taiwan5 sites
Changhua Christian Medical Foundation Changhua Christian Hospital
Changhua, 500
Kaohsiung Medical University Hospital
Kaohsiung City, 807
China Medical University Hospital
Taichung, 40447
Chi Mei Medical Center, Liouying
Tainan, 736
National Taiwan University Hospital
Taipei
Japan4 sites
University of Fukui Hospital
Fukui, 910-1193
Japanese Red Cross Society Himeji Hospital
Himeji, 670-8540
Kobe City Medical Center General Hospital
Kobe
Matsuyama Red Cross Hospital
Matsuyama, Ehime, 790-8524
Australia3 sites
Royal Adelaide Hospital
Adelaide, South Australia, 5000
Flinders Medical Centre
Bedford Park, South Australia, 5042
Royal Prince Alfred Hospital
Camperdown, New South Wales, 2050
Israel3 sites
Rabin Medical Center - PPDS
Petah Tikva, 49100
Kaplan Medical Center
Rehovot, 7610000
Shamir Medical Center Assaf Harofeh
Tzrifin, 70300
Poland3 sites
Uniwersyteckie Centrum Kliniczne
Gdansk, 80-214
Instytut Hematologii i Transfuzjologii
Warsaw, Masovian Voivodeship, 02-776
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
Wroclaw, Lower Silesian Voivodeship, 50-367
United States2 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Norton Cancer Institute - Suburban
Louisville, Kentucky, 40207
Austria2 sites
Salzburger Landeskliniken
Salzburg, 5020
Krankenhaus Hietzing mit Neurologischem Zentrum Rosenhugel
Vienna, 1130
Canada2 sites
University Health Network
Toronto, Ontario, M5G 2M9
Cancer Care Manitoba
Winnipeg, Manitoba, R3E 0V9
Mexico2 sites
SINACOR
Culiacán, 80230
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
México, 14000
Netherlands2 sites
VU Medisch Centrum
Amsterdam, North Holland, 1081 HV
Universitair Medisch Centrum Groningen
Nijmegen, 6525 GA
Russia2 sites
Kaluga Regional Clinical Hospital
Kaluga, 248007
City Clinical Hospital # 40
Moscow, 129301
United Kingdom1 site
Birmingham Heartlands Hospital
Birmingham, West Midlands, B9 5SS
About this study
Official title: A Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study of AG-120 in Combination With Azacitidine in Subjects ≥ 18 Years of Age With Previously Untreated Acute Myeloid Leukemia With an IDH1 Mutation
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
- Being tested
- AG-120, Placebo, Azacitidine
- Keywords
- Acute Myeloid Leukemia, Leukemia, Azacitidine, AG-120, ivosidenib
- Medical subject headings
- Leukemia, Myeloid, Acute, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AG-120Drug
Also called Ivosidenib
Tablets administered orally
PlaceboDrug
Tablets administered orally
AzacitidineDrug
Also called Vidaza®
Administered SC or IV
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 . Receives: Drug: Placebo; Drug: Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to Week 24
Secondary outcomes (32)
Complete Remission Rate (CR Rate)
CR rate is defined as the proportion of participants who achieve a CR. A Cochran-Mantel-Haenszel (CMH) test will be used to compare CR rate between the 2 treatment arms.
Measured: Up to approximately 52 months
Overall Survival (OS)
OS is defined as the time from date of randomization to the date of death due to any cause. Kaplan-Meier (KM) curves and KM estimates of OS will be presented for each treatment arm.
Measured: Up to approximately 52 months
CR + Complete Remission With Partial Hematologic (CRh) Rate
CR + CRh rate is defined as the proportion of participants who achieve a CR or CRh. CRh is defined as a CR with partial recovery of peripheral blood counts (less than 5% bone marrow blasts, absolute neutrophil count (ANC) greater than 0.5 × 10^9/liter (L) 500/microliter (μL)], and platelets greater than 50 × 10^9/L [50,000/μL]). A CMH test will be used to compare the CR + CRh rate between the 2 treatment arms.
Measured: Up to approximately 52 months
Objective Response Rate (ORR)
ORR is defined as the rate of CR, CR with incomplete hematologic recovery (CRi) (including CR with incomplete platelet recovery [CRp]), partial remission (PR), and morphologic leukemia-free state (MLFS). The best response is calculated using the following hierarchy: CR, followed by CRi (including CRp), followed by PR and MLFS. A summary of best response by treatment arm will be produced. A CMH test will be used to compare ORR between the 2 treatment arms.
Measured: Up to approximately 52 months
CR + CRi (Including CRp) Rate
The CR + CRi (including CRp) rate is defined as the proportion of participants who achieve a CR or CRi (including CRp). A CMH test will be used to compare the CR + CRi (including CRp) rate between the 2 treatment arms.
Measured: Up to approximately 52 months
Duration of CR (DOCR)
DOCR will be calculated as the date of the first occurrence of CR to the date of first documented disease relapse, or death. DOCR is only defined for participants who achieve a CR.
Measured: Up to approximately 52 months
Duration of CRh (DOCRh)
DOCRh will be calculated as the date of the first occurrence of CR or CRh to the date of first documented disease relapse or death. DOCRh is only defined for participants who achieve a CR or CRh.
Measured: Up to approximately 52 months
Duration of Response (DOR)
DOR will be calculated as the date of the first response to the date of first documented disease relapse, disease progression, or death. DOR is only defined for participants who achieve a CR, CRi (including CRp), PR, and/or MLFS.
Measured: Up to approximately 52 months
Duration of CRi (DOCRi)
DOCRi will be calculated as the date of the first occurrence of CR or CRi (including CRp) to the date of the first documented relapse or death. DOCRi is only defined for participants who achieve a CR or CRi (including CRp).
Measured: Up to approximately 52 months
Time to CR (TTCR)
TTCR will be assessed from the date of randomization to the date of first occurrence of CR. TTCR is only defined for participants who achieve a CR.
Measured: Up to approximately 52 months
Time to CRh (TTCRh)
TTCRh will be assessed from the date of randomization to the date of first occurrence of CR or CRh. TTCRh is only defined for participants who achieve a CR or CRh.
Measured: Up to approximately 52 months
Time to Response (TTR)
TTR will be assessed from the date of randomization to the date of the first response. TTR is only defined for participants who achieve a CR, CRi (including CRp), PR, and/or MLFS.
Measured: Up to approximately 52 months
Time to CRi (TTCRi)
TTCRi will be assessed from the date of randomization to the date of first occurrence of CR or CRi (including CRp). TTCRi is only defined for participants who achieve a CR or CRi (including CRp).
Measured: Up to approximately 52 months
Percentage of Participants With Abnormalities in Vital Sign Measurements
Vital signs will include body temperature, respiratory rate, blood pressure, and heart rate.
Measured: Up to approximately 52 months
Percentage of Participants With Abnormalities in Eastern Cooperative Oncology Group Performance Status (ECOG PS)
Measured: Up to approximately 52 months
Percentage of Participants With Abnormalities in 12-lead Electrocardiograms (ECGs)
Measured: Up to approximately 52 months
Percentage of Participants With Abnormalities in Echocardiogram (ECHO) or Multi-Gated Acquisition (MUGA) for Left Ventricular Ejection Fraction (LVEF)
LVEF is determined by ECHO or MUGA scan in participants.
Measured: Up to approximately 52 months
Percentage of Participants With Abnormalities in Clinical Laboratory Tests
Clinical laboratory assessments will include hematology, serum chemistry, coagulation.
Measured: Up to approximately 52 months
Percentage of Participants With Adverse Events (AEs)
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered an investigational medicinal product; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug.
Measured: Up to approximately 52 months
Percentage of Participants With AEs of Special Interest (AESIs)
AESIs are AEs that are not solicited local or systemic AEs, they are predefined AEs that required close monitoring and prompt reporting to the sponsor. AESIs include protocol-specified QT prolongation, isocitrate dehydrogenase (IDH) differentiation syndrome and leukocytosis.
Measured: Up to approximately 52 months
Percentage of Participants With Serious Adverse Events (SAEs)
An SAE is defined as an untoward medical occurrence, significant hazard, contraindication, side effect or precaution that at any dose: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
Measured: Up to approximately 52 months
Percentage of Participants With Adverse Events Leading to Discontinuation or Death
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered an investigational medicinal product; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug.
Measured: Up to approximately 52 months
Percentage of Participants Using Concomitant Medications
Participants receiving concomitant medications will be adequately monitored by ECG controls, drug concentration (where applicable), and serum electrolytes (i.e., potassium and magnesium).
Measured: Up to approximately 52 months
Units of Platelets and Red Blood Cells (RBC) Infused
All measures that are indicative of clinical benefit are measured like number of units of platelet and RBC infused.
Measured: Up to approximately 52 months
Rate of Infection
Measured: Up to approximately 52 months
Number of Days Spent Hospitalized
Measured: Up to approximately 52 months
Change From Baseline in the European Organisation for Research and Treatment of Cancer (EORTC) QLC-C30 Questionnaire
The EORTC QLQ-C30 questionnaire measures quality of life and consists of 30 questions that are incorporated into 5 functional domains (physical, role, cognitive, emotional, and social); a global health status/global quality of life; 3 symptom scales (fatigue, pain, and nausea and vomiting); and 6 single items that assess additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) and the perceived financial burden of treatment experienced by participants with cancer.
Measured: Up to approximately 52 months
Change From Baseline in the EORTC EQ-5D-5L Questionnaire
The EORTC EQ-5D-5L questionnaire measures quality of life and spans 5 dimensions, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, which are used to build a composite of the participant's health status.
Measured: Up to approximately 52 months
Percentage of Participants With CR With IDH1 Mutation Clearance (MC)
CR with IDH1 MC is defined as a response of CR where there is no evidence of the IDH1 mutation by molecular techniques to below the level of detection (0.02%-0.04%) for ≥1 on-treatment time point. A CMH test will be used to compare the rate of CR between 2 treatment arms.
Measured: Up to approximately 52 months
Percentage of Participants With Drug Exposure, Dose Modifications and Dose Intensities
The number of doses administered, total dose, duration of treatment, dose intensity, and the proportion of participants with dose modifications, will be summarized by treatment arm.
Measured: Up to approximately 52 months
Circulating Plasma Concentration of AG-120
Serial blood samples will be drawn before and after dosing of study treatment in order to determine circulating plasma concentrations.
Measured: Up to approximately 52 months
Circulating Plasma Concentration of 2-HG
Serial blood samples will be drawn before and after dosing of study treatment in order to determine circulating plasma concentrations.
Measured: Up to approximately 52 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2017
- Study start26 Jun 2017
- Primary completion18 Mar 2021
- Study completion30 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Newly Diagnosed Acute Myeloid Leukemia (AML)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 146 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institut de Recherches Internationales Servier
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03173248
- Sponsor's protocol ID
- AG120-C-009
- Acronym
- AGILE
- Status last verified
- Jun 2026
- First submitted
- 30 May 2017
- Last updated
- 29 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data. Access can be requested for all interventional clinical studies: * used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US). * where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope. In addition, access can be requested for all interventional clinical studies in patients: * sponsored by Servier * with a first patient enrolled as of 1 January 2004 onwards * for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.
Publications
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.
PubMed 35443108Montesinos 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.
PubMed 40706052Woods 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.
PubMed 38010220
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study of AG-120 in Combination With Azacitidine in Subjects ≥ 18 Years of Age With Previously Untreated Acute Myeloid Leukemia With an IDH1 Mutation
- ClinicalTrials.gov ID
- NCT03173248
- Acronym / sponsor ID
- AGILE / AG120-C-009
- 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
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 146 participants (actual)
- Lead sponsor
- Institut de Recherches Internationales ServierUniversity, hospital or other
- Study start
- 26 Jun 2017 (actual)
- Primary completion
- 18 Mar 2021 (actual)
- Study completion
- 30 Jun 2026 (estimated)
- First posted
- 1 Jun 2017 (actual)
- Results
- Posted 23 Mar 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AG-120 + Azacitidine | Experimental | Drug: AG-120, Drug: AzacitidineParticipants 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. |
| Placebo + Azacitidine | Placebo comparator | Drug: Placebo, Drug: AzacitidineParticipants 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 . |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AG-120Also: IvosidenibTablets administered orally | Drug | AG-120 + Azacitidine |
| PlaceboTablets administered orally | Drug | Placebo + Azacitidine |
| AzacitidineAlso: Vidaza®Administered SC or IV | Drug | AG-120 + Azacitidine, Placebo + Azacitidine |
Primary outcome
Event-Free Survival (EFS)
Time frame: Up to Week 24
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.
32 secondary outcomes
Complete Remission Rate (CR Rate)
Time frame: Up to approximately 52 months
Overall Survival (OS)
Time frame: Up to approximately 52 months
CR + Complete Remission With Partial Hematologic (CRh) Rate
Time frame: Up to approximately 52 months
Objective Response Rate (ORR)
Time frame: Up to approximately 52 months
CR + CRi (Including CRp) Rate
Time frame: Up to approximately 52 months
Duration of CR (DOCR)
Time frame: Up to approximately 52 months
Duration of CRh (DOCRh)
Time frame: Up to approximately 52 months
Duration of Response (DOR)
Time frame: Up to approximately 52 months
Duration of CRi (DOCRi)
Time frame: Up to approximately 52 months
Time to CR (TTCR)
Time frame: Up to approximately 52 months
Time to CRh (TTCRh)
Time frame: Up to approximately 52 months
Time to Response (TTR)
Time frame: Up to approximately 52 months
Time to CRi (TTCRi)
Time frame: Up to approximately 52 months
Percentage of Participants With Abnormalities in Vital Sign Measurements
Time frame: Up to approximately 52 months
Percentage of Participants With Abnormalities in Eastern Cooperative Oncology Group Performance Status (ECOG PS)
Time frame: Up to approximately 52 months
Percentage of Participants With Abnormalities in 12-lead Electrocardiograms (ECGs)
Time frame: Up to approximately 52 months
Percentage of Participants With Abnormalities in Echocardiogram (ECHO) or Multi-Gated Acquisition (MUGA) for Left Ventricular Ejection Fraction (LVEF)
Time frame: Up to approximately 52 months
Percentage of Participants With Abnormalities in Clinical Laboratory Tests
Time frame: Up to approximately 52 months
Percentage of Participants With Adverse Events (AEs)
Time frame: Up to approximately 52 months
Percentage of Participants With AEs of Special Interest (AESIs)
Time frame: Up to approximately 52 months
Percentage of Participants With Serious Adverse Events (SAEs)
Time frame: Up to approximately 52 months
Percentage of Participants With Adverse Events Leading to Discontinuation or Death
Time frame: Up to approximately 52 months
Percentage of Participants Using Concomitant Medications
Time frame: Up to approximately 52 months
Units of Platelets and Red Blood Cells (RBC) Infused
Time frame: Up to approximately 52 months
Rate of Infection
Time frame: Up to approximately 52 months
Number of Days Spent Hospitalized
Time frame: Up to approximately 52 months
Change From Baseline in the European Organisation for Research and Treatment of Cancer (EORTC) QLC-C30 Questionnaire
Time frame: Up to approximately 52 months
Change From Baseline in the EORTC EQ-5D-5L Questionnaire
Time frame: Up to approximately 52 months
Percentage of Participants With CR With IDH1 Mutation Clearance (MC)
Time frame: Up to approximately 52 months
Percentage of Participants With Drug Exposure, Dose Modifications and Dose Intensities
Time frame: Up to approximately 52 months
Circulating Plasma Concentration of AG-120
Time frame: Up to approximately 52 months
Circulating Plasma Concentration of 2-HG
Time frame: Up to approximately 52 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 35443108Montesinos 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.
- Derived from this study: PubMed 40706052Montesinos 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.
- Derived from this study: PubMed 38010220Woods 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.
- Individual participant dataSharing planned: Yes. Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data. Access can be requested for all interventional clinical studies: * used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US). * where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope. In addition, access can be requested for all interventional clinical studies in patients: * sponsored by Servier * with a first patient enrolled as of 1 January 2004 onwards * for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
90 sites in 20 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing AG-120 and Azacitidine in people with Newly Diagnosed Acute Myeloid Leukemia (AML) and Untreated AML, run by Institut de Recherches Internationales Servier at 90 sites in 20 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 29 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 90 sites in France, Spain, Germany, Italy, Brazil and 15 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event-Free Survival (EFS) (time frame: Up to Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03173248, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2026.