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Relapsed or Refractory Acute Myeloid Leukemia (AML)Phase 1NCT02074839

Study of Orally Administered AG-120 in Subjects With Advanced Hematologic Malignancies With an IDH1 Mutation

A Phase 1 study testing AG-120 in people with Relapsed or Refractory Acute Myeloid Leukemia (AML) and Untreated AML, run by Institut de Recherches Internationales Servier at 30 sites in 2 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

The purpose of this Phase I, multicenter study is to evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity of AG-120 in advanced hematologic malignancies that harbor an IDH1 mutation. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
AG-120
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
291 participants
Where
30 sitesin 2 countries
Study dates
1 Mar 2014to 31 Dec 2026
Phase
Phase 1
Are there results?
Not yet: the study is under way

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

  • Subject must be ≥18 years of age.
  • Subjects must have documented IDH1 R132 gene-mutated advanced hematologic malignancy based on local or central evaluation.
  • Subjects must be amenable to serial bone marrow biopsies, peripheral blood sampling, and urine sampling during the study.
  • Subjects must have ECOG PS of 0 to 2.
  • Platelet count ≥20,000/µL (Transfusions to achieve this level are allowed).
  • Subjects must have adequate hepatic function as evidenced by: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤3.0 × ULN, unless considered due to leukemic disease and serum total bilirubin ≤1.5 x upper limit of normal (ULN), unless considered due to Gilbert's disease or leukemic disease
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  • Subjects must have adequate renal function as evidenced by a serum creatinine ≤2.0 × ULN or creatinine clearance >40mL/min based on Cockroft-Gault glomerular filtration rate (GFR)
  • Subjects must be recovered from any clinically relevant toxic effects of any prior surgery, radiotherapy, or other therapy intended for the treatment of cancer.
  • Female subjects with reproductive potential must have a negative serum pregnancy test within 7 days prior to the start of therapy and on the first day of study drug administration.

Who cannot join

  • Subjects who have undergone hematopoietic stem cell transplant (HSCT) within 60 days of the first dose of AG-120, or subjects on immunosuppressive therapy post HSCT at the time of screening, or with clinically significant graft-versus-host disease (GVHD). (The use of a stable dose of oral steroids post HSCT and/or topical for ongoing skin GVHD is permitted.)
  • Subjects who received systemic anticancer therapy or radiotherapy <14 days prior to their first day of study drug administration. (Hydroxyurea is allowed prior to enrollment and after the start of AG-120).
  • Subjects who received an investigational agent <14 days prior to their first day of study drug administration.
  • Subjects who are pregnant or breastfeeding.
  • Subjects with an active severe infection or with an unexplained fever >38.5°C during screening visits or on their first day of study drug administration (at the discretion of the Investigator, subjects with tumor fever may be enrolled).
  • Subjects with New York Heart Association (NYHA) Class III or IV congestive heart failure or LVEF <40% by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan within approximately 28 days of C1D1.
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  • Subjects with a history of myocardial infarction within the last 6 months of screening.
  • Subjects with a known unstable or uncontrolled angina pectoris.
  • Subjects with a known history of severe and/or uncontrolled ventricular arrhythmias.
  • Subjects with known unstable or uncontrolled angina pectoris.
  • Subjects with heart-rate corrected QT (QTc) interval ≥450 ms or other factors that increase the risk of QT prolongation or arrhythmic events.
  • Patients taking medications that are known to prolong the QT interval
  • Subjects with known infection with human immunodeficiency virus (HIV) or active hepatitis B or C.
  • Subjects with clinical symptoms suggesting active central nervous system (CNS) leukemia or known CNS leukemia. Evaluation of cerebrospinal fluid is only required if there is a clinical suspicion of CNS involvement by leukemia during screening.
  • Subjects with immediately life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation.

Trial locations and contacts

30 sites in 2 countries. Contact the study team or a site near you to ask about taking part.

Institut de Recherches Internationales Servier Clinical Studies Department contact

+33 1 55 72 43 66

scientificinformation@servier.com

30 sites in 2 countries

United States26 sites, 3 recruiting

  • Emory University

    Atlanta, Georgia, 30322

    Active, not recruiting

  • University of Colorado Denver

    Aurora, Colorado, 80045

    Terminated

  • John Hopkins Cancer Center

    Baltimore, Maryland, 21287

    Active, not recruiting

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

    Active, not recruiting

  • Massachusetts General Hospital

    Boston, Massachusetts, 02214

    Terminated

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

    Terminated

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

    Recruiting

  • Northwestern University Medical Hospital

    Chicago, Illinois, 60611

    Terminated

  • Cleveland Clinic

    Cleveland, Ohio, 44124

    Withdrawn

  • Ohio State University

    Columbus, Ohio, 43210

    Terminated

  • UT Southwestern Medical Center

    Dallas, Texas, 75390

    Recruiting

  • Karmanos Cancer Center

    Detroit, Michigan, 48201

    Terminated

  • City of Hope

    Duarte, California, 91010

    Active, not recruiting

  • Duke Cancer Center

    Durham, North Carolina, 27705

    Terminated

  • MD Anderson Cancer Center

    Houston, Texas, 77030

    Recruiting

  • Mayo Clinic-Jacksonville

    Jacksonville, Florida, 32224

    Terminated

  • University of California-Los Angeles

    Los Angeles, California, 90095

    Terminated

  • University of Miami

    Miami, Florida, 33136

    Terminated

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

    Terminated

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10021

    Active, not recruiting

  • Cornell Cancer Center

    New York, New York, 10065

    Terminated

  • Mayo Clinic-AZ

    Phoenix, Arizona, 85259

    Terminated

  • Oregon Health and Science University

    Portland, Oregon, 97239

    Terminated

  • University of California-San Francisco

    San Francisco, California, 94143

    Terminated

  • Washington University

    St Louis, Missouri, 63110

    Terminated

  • Moffit Cancer Center

    Tampa, Florida, 33612

    Active, not recruiting

Other trials in United States

France4 sites, 3 recruiting

  • Hopital La Timone

    Marseille

    Terminated

  • Hopital Haut-Leveque

    Pessac, 33600

    Recruiting

  • Central Lyon Sud

    Pierre-Bénite, 69310

    Recruiting

  • Institute Gustave Roussly (IGR)

    Villejuif, 94800

    Recruiting

Other trials in France

About this study

Official title: A Phase I, Multicenter, Open-Label, Dose-Escalation and Expansion, Safety, Pharmacokinetic, Pharmacodynamic, and Clinical Activity Study of Orally Administered AG-120 in Subjects With Advanced Hematologic Malignancies With an IDH1 Mutation

The purpose of this Phase I, multicenter study is to evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity of AG-120 in advanced hematologic malignancies that harbor an IDH1 mutation. The first portion of the study is a dose escalation phase where cohorts of patients will receive ascending oral doses of AG-120 to determine maximum tolerated dose (MTD) and/or the recommended Phase II dose. The second portion of the study is a dose expansion phase where four cohorts of patients will receive AG-120 to further evaluate the safety, tolerability, and clinical activity of the recommended Phase II dose. Additionally, the study includes a substudy evaluating the safety and tolerability, clinical activity, pharmacokinetics, and pharmacodynamics of AG-120 in subjects with relapsed or refractory myelodysplastic syndrome with an IDH1 mutation. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

Being tested
AG-120
Keywords
acute myeloid leukemia, AML, myelodysplastic syndrome, MDS, hematologic malignancies, IDH, Untreated AML, IDH1, relapsed AML, refractory AML
Medical subject headings
Recurrence, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Hematologic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AG-120Drug

    AG-120 administered continuously as a single agent dosed orally every day of a 28-day cycle. Subjects may continue treatment with AG-120 until disease progression, development of other unacceptable toxicity or hematopoietic stem cell transplant.

Study groups in NCT02074839
Study groupRoleWhat they receive
AG-120ExperimentalAG-120 administered continuously as a single agent dosed orally every day of a 28-day cycle.
Receives: Drug: AG-120

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety/tolerability: incidence of adverse events.

    Measured: up to 26 weeks, on average

  2. Maximum Tolerated Dose and/or the recommended Phase II dose of AG-120 in subjects with advanced hematologic malignancies.

    Measured: up to 26 weeks, on average

  3. Assess clinical activity of AG-120 in subjects with relapsed or refractory AML who are enrolled in the Expansion Phase.

    Measured: up to 26 weeks, on average

  4. Safety/tolerability of treatment with AG-120 in subjects with relapsed or refractory myelodysplastic syndrome.

    Measured: up to 26 weeks, on average

  5. Assess clinical activity of AG-120 in subjects with relapsed or refractory myelodysplastic syndrome.

    Measured: up to 26 weeks, on average

Secondary outcomes (8)

  1. Dose Limiting Toxicities of AG-120 in subjects with advanced hematologic malignancies.

    Measured: up to 26 weeks, on average

  2. Pharmacokinetics of AG-120 in subjects with advanced hematologic malignancies.

    Descriptive statistics will be used to summarize PK parameters for each dose group and, where appropriate, for the entire population. Such parameters will include (but are not limited to) maximum concentration (Cmax), time to maximum concentration (Tmax), AUC, elimination half-life, and the fraction of drug excreted unchanged in the urine.

    Measured: up to 26 weeks, on average

  3. Pharmacodynamic relationship of AG-120 and 2-HG.

    The potential relationship between plasma exposure of AG-120 and plasma, urine, or bone marrow 2-HG levels will be explored with descriptive and graphical methods.

    Measured: up to 26 weeks, on average

  4. Clinical Activity of AG-120 in advanced hematologic malignancies according to the 2003 revised IWG criteria for AML or the 2006 modified IWG criteria for MDS or MDS/myeloproliferative neoplasms (MPN).

    Measured: up to 26 weeks, on average

  5. Serial blood sampling at specified time points for determination of plasma concentration-time profiles and PK parameters (Cmax) of AG-120 in subjects with R/R MDS.

    Measured: up to 26 weeks, on average

  6. Serial blood sampling at specified time points for determination of plasma concentration-time profiles and PK parameters (Tmax) of AG-120 in subjects with R/R MDS.

    Measured: up to 26 weeks, on average

  7. Serial blood sampling at specified time points for determination of plasma concentration-time profiles and PK parameters (AUC) of AG-120 in subjects with R/R MDS.

    Measured: up to 26 weeks, on average

  8. Blood and bone marrow sampling at specified time points for determination of 2-HG levels to characterize the percent of 2-HG inhibition of AG-120 in plasma and bone marrow.

    Measured: up to 26 weeks, on average

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Feb 2014 (estimated)
  2. Study start1 Mar 2014
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion31 Dec 2026 (estimated)

Resources

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
291 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02074839
Sponsor's protocol ID
AG120-C-001
Status last verified
Jun 2026
First submitted
21 Feb 2014
Last updated
15 Jun 2026
Results posted
No
Data monitoring committee
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

  • Sun M, Yin Q, Liang Y, Chang C, Zheng J, Li J, Ji C, Qiu H, Li J, Gong Y, Luo S, Zhang Y, Chen R, Shen Z, Yue Z, Wang S, Shi Q, Yang J, Jin J, Wang J. Ivosidenib in Chinese patients with relapsed or refractory isocitrate dehydrogenase 1 mutated acute myeloid leukemia: a registry study. Blood Sci. 2024 Jun 20;6(3):e00196. doi: 10.1097/BS9.0000000000000196. eCollection 2024 Jul.

    PubMed 38911469

  • DiNardo CD, Roboz GJ, Watts JM, Madanat YF, Prince GT, Baratam P, de Botton S, Stein A, Foran JM, Arellano ML, Sallman DA, Hossain M, Marchione DM, Bai X, Patel PA, Kapsalis SM, Garcia-Manero G, Fathi AT. Final phase 1 substudy results of ivosidenib for patients with mutant IDH1 relapsed/refractory myelodysplastic syndrome. Blood Adv. 2024 Aug 13;8(15):4209-4220. doi: 10.1182/bloodadvances.2023012302.

    PubMed 38640348

  • Jiang X, Wada R, Poland B, Kleijn HJ, Fan B, Liu G, Liu H, Kapsalis S, Yang H, Le K. Population pharmacokinetic and exposure-response analyses of ivosidenib in patients with IDH1-mutant advanced hematologic malignancies. Clin Transl Sci. 2021 May;14(3):942-953. doi: 10.1111/cts.12959. Epub 2021 Jan 25.

    PubMed 33493392

  • Choe S, Wang H, DiNardo CD, Stein EM, de Botton S, Roboz GJ, Altman JK, Mims AS, Watts JM, Pollyea DA, Fathi AT, Tallman MS, Kantarjian HM, Stone RM, Quek L, Konteatis Z, Dang L, Nicolay B, Nejad P, Liu G, Zhang V, Liu H, Goldwasser M, Liu W, Marks K, Bowden C, Biller SA, Attar EC, Wu B. Molecular mechanisms mediating relapse following ivosidenib monotherapy in IDH1-mutant relapsed or refractory AML. Blood Adv. 2020 May 12;4(9):1894-1905. doi: 10.1182/bloodadvances.2020001503.

    PubMed 32380538

  • Fan B, Dai D, DiNardo CD, Stein E, de Botton S, Attar EC, Liu H, Liu G, Lemieux I, Agresta SV, Yang H. Clinical pharmacokinetics and pharmacodynamics of ivosidenib in patients with advanced hematologic malignancies with an IDH1 mutation. Cancer Chemother Pharmacol. 2020 May;85(5):959-968. doi: 10.1007/s00280-020-04064-6. Epub 2020 Apr 15.

    PubMed 32296873

  • Roboz GJ, DiNardo CD, Stein EM, de Botton S, Mims AS, Prince GT, Altman JK, Arellano ML, Donnellan W, Erba HP, Mannis GN, Pollyea DA, Stein AS, Uy GL, Watts JM, Fathi AT, Kantarjian HM, Tallman MS, Choe S, Dai D, Fan B, Wang H, Zhang V, Yen KE, Kapsalis SM, Hickman D, Liu H, Agresta SV, Wu B, Attar EC, Stone RM. Ivosidenib induces deep durable remissions in patients with newly diagnosed IDH1-mutant acute myeloid leukemia. Blood. 2020 Feb 13;135(7):463-471. doi: 10.1182/blood.2019002140.

    PubMed 31841594

  • DiNardo CD, Stein EM, de Botton S, Roboz GJ, Altman JK, Mims AS, Swords R, Collins RH, Mannis GN, Pollyea DA, Donnellan W, Fathi AT, Pigneux A, Erba HP, Prince GT, Stein AS, Uy GL, Foran JM, Traer E, Stuart RK, Arellano ML, Slack JL, Sekeres MA, Willekens C, Choe S, Wang H, Zhang V, Yen KE, Kapsalis SM, Yang H, Dai D, Fan B, Goldwasser M, Liu H, Agresta S, Wu B, Attar EC, Tallman MS, Stone RM, Kantarjian HM. Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML. N Engl J Med. 2018 Jun 21;378(25):2386-2398. doi: 10.1056/NEJMoa1716984. Epub 2018 Jun 2.

    PubMed 29860938

  • Birendra KC, DiNardo CD. Evidence for Clinical Differentiation and Differentiation Syndrome in Patients With Acute Myeloid Leukemia and IDH1 Mutations Treated With the Targeted Mutant IDH1 Inhibitor, AG-120. Clin Lymphoma Myeloma Leuk. 2016 Aug;16(8):460-5. doi: 10.1016/j.clml.2016.04.006. Epub 2016 May 5.

    PubMed 27245312

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AG-120 in people with Relapsed or Refractory Acute Myeloid Leukemia (AML) and Untreated AML, run by Institut de Recherches Internationales Servier at 30 sites in 2 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 9 inclusion and 15 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: looking for participants now, as of the sponsor's last update on 15 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 30 sites in United States, France. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Institut de Recherches Internationales Servier Clinical Studies Department (+33 1 55 72 43 66, scientificinformation@servier.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety/tolerability: incidence of adverse events. (time frame: up to 26 weeks, on average). The study lists 5 primary outcomes in all. 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 NCT02074839, which also lists 8 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 15 Jun 2026.

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