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AzTrials

Newly Diagnosed Acute Myeloid Leukemia (AML)Phase 1NCT02632708

Safety Study of AG-120 or AG-221 in Combination With Induction and Consolidation Therapy in Participants With Newly Diagnosed Acute Myeloid Leukemia (AML) With an IDH1 and/or IDH2 Mutation

A Phase 1 study testing AG-120, AG-221 and cytarabine in people with Newly Diagnosed Acute Myeloid Leukemia (AML) and Untreated AML, run by Institut de Recherches Internationales Servier at 17 sites in 3 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

The purpose of this Phase I, multicenter, clinical trial is to evaluate the safety of AG-120 and AG-221 when given in combination with standard AML induction and consolidation therapy. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
AG-120, AG-221 and cytarabine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
153 participants
Where
17 sitesin 3 countries
Study dates
31 Dec 2015to 24 Jul 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

  • Participants must ≥18 years of age
  • Previously untreated AML (de novo or secondary) defined according to World Health Organization (WHO) criteria, excluding acute promyelocytic leukemia (APL) [AML with t(15;17)], with locally documented IDH1 and/or IDH2 gene mutation scheduled for induction therapy followed by consolidation therapy. Participants with secondary AML is defined as AML arising after myelodysplastic syndromes (MDSs) or other antecedent hematologic disorders (AHDs) or AML arising after exposure to genotoxic injury including radiation and/or chemotherapy are also eligible. Participants may have had previous treatment for MDS or other AHD, including hypomethylating agents (HMAs), provided it was ≥ 14 days prior to study drug initiation
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 to 2
  • Adequate hepatic function as evidenced by: serum total bilirubin ≤1.5 × upper limit of normal (ULN) unless considered due to Gilbert's disease, a gene mutation in UGT1A1 (only for patients who will be receiving AG-221), or leukemic involvement following approval by the study Sponsor; aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤3.0 × ULN, unless considered due to leukemic involvement following approval by the study Sponsor
  • Adequate renal function as evidenced by serum creatinine ≤2.0 × ULN or creatinine clearance 40 mL/min based on the Cockcroft-Gault glomerular filtration rate (GFR)
  • Agree to serial blood and bone marrow sampling
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  • Meet any criteria necessary for the safe and proper use of the induction and consolidation agents involved in this trial
  • Able to understand and willing to sign an informed consent form. A legally authorized representative may consent on behalf of a participant who is otherwise unable to provide informed consent, if acceptable to, and approved by, the site's Institutional Review Board (IRB)/Independent Ethics Committee (IEC).
  • Female participants with reproductive potential must agree to undergo a medically supervised pregnancy test prior to starting study drug. The first pregnancy test will be performed at screening (within 7 days prior to first study drug administration). A pregnancy test should also be performed on the day of the first study drug administration and confirmed negative prior to dosing as well as before dosing on Day 1 of all subsequent cycles
  • Female participants with reproductive potential must have a negative serum pregnancy test within 7 days prior to the start of the therapy. Participants with reproductive potential are defined as sexually mature women who have not undergone a hysterectomy, bilateral oophorectomy or tubal occlusion or who have not been naturally postmenopausal for at least 24 consecutive months. Females of reproductive potential as well as fertile men and their partners who are female of reproductive potential must agree to abstain from sexual intercourse or to use one highly effective form (for participants receiving AG-221) or two highly effective forms (for participants receiving AG-120) of contraception from the time of giving informed consent, during the study, and for 2 months (for participants receiving AG-221) and for 4 months (for participants receiving AG-120) following the last dose of AG-120 or AG-221 (females and males). A highly effective form of contraception is defined as hormonal oral contraceptives, injectables, patches, intrauterine devices, double-barrier method (e.g., synthetic condoms, diaphragm or cervical cap with spermicidal foam, cream, or gel) or male partner sterilization

Who cannot join

  • Prior chemotherapy for AML. Hydroxyurea is allowed prior to enrollment for the control of peripheral leukemic blasts in participants with leukocytosis; hydroxyurea may be allowed on study with study Sponsor approval
  • Taking medications with narrow therapeutic windows, unless they can be transferred to other medications prior to enrolling or unless the medications can be properly monitored during the study
  • Taking known strong cytochrome P450 (CYP) 3A4 inducers, unless they can be transferred to other medications prior to enrolling. For participants taking AG-120, systemic administration of a moderate or strong CYP3A4 inhibitor requires careful monitoring of the heart rate-corrected QT interval (QTc) using Fridericia's formula (QTcF)
  • Taking P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) or OATP1B1/1B3 transporter-sensitive substrate medications unless they can be transferred to alternative medications within ≥5 half-lives prior to administration of AG-221, or unless the medications can be adequately monitored during the study. There are no restrictions regarding the co-administration of such medications with AG-120.
  • Pregnant or breastfeeding
  • Uncontrolled active infection or uncontrolled invasive fungal infection (positive blood or tissue culture). An infection controlled with an approved or closely monitored antibiotic/antifungal treatment is allowed
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  • Prior history of malignancy, other than MDS or AML, unless the participant has been free of the disease for ≥1 year prior to the start of study treatment However, participants with the following history/concurrent conditions are allowed: basal or squamous cell carcinoma of the skin; carcinoma in situ of the cervix; carcinoma in situ of the breast; incidental histologic finding of prostate cancer
  • Significant active cardiac disease within 6 months prior to the start of study treatment, including New York Heart Association (NYHA) Class III or IV congestive heart failure; myocardial infarction, unstable angina and/or stroke; or left ventricular ejection fraction (LVEF) <40% by echocardiogram (ECHO), or by other methods according to institutional practice, obtained within 28 days prior to the start of study treatment
  • QTc interval using Fridericia's formula (QTcF) ≥450 milliseconds (msec) or other factors that increase the risk of QT interval prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome). Bundle branch block and prolonged QTc are permitted with approval of the study Sponsor
  • 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 (If equivalent medication is not available QTc will be closely monitored)
  • Known infection caused by human immunodeficiency virus (HIV) or active hepatitis B or C
  • Dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of orally administered drugs
  • Clinical symptoms suggestive of active central nervous system (CNS) leukemia or known CNS leukemia. Evaluation of cerebrospinal fluid (CSF) during screening is required only if there is a clinical suspicion of CNS involvement by leukemia during screening.
  • Immediate life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation
  • Any other medical or psychological condition deemed by the Investigator to be likely to interfere with a participant's ability to give informed consent or participate in the study

Trial locations and contacts

17 sites in 3 countries.

17 sites in 3 countries

United States14 sites

  • University of Colorado

    Aurora, Colorado, 80045

  • Johns Hopkins University

    Baltimore, Maryland, 21231

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02114

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Medical University of South Carolina - PPDS

    Charleston, South Carolina, 29425-0001

  • University of Chicago

    Chicago, Illinois, 60637

  • Ohio State University

    Columbus, Ohio, 43210

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • City of Hope

    Duarte, California, 91010

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • UCLA Medical Center

    Los Angeles, California, 90024

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10021

Other trials in United States

Netherlands2 sites

  • VU Medisch Centrum

    Amsterdam, 1081 HV

  • Erasmus MC

    Rotterdam, 3075 EA

Other trials in Netherlands

Germany1 site

  • Universitatsklinikum Ulm

    Ulm, 89081

Other trials in Germany

About this study

Official title: A Phase 1, Multicenter, Open-Label, Safety Study of AG-120 or AG-221 in Combination With Induction Therapy and Consolidation Therapy in Patients With Newly Diagnosed Acute Myeloid Leukemia With an IDH1 and/or IDH2 Mutation

The purpose of this Phase I, multicenter, clinical trial is to evaluate the safety of AG-120 and AG-221 when given in combination with standard AML induction and consolidation therapy. The study plans to evaluate up to 2 dose levels of AG-120 in participants with an isocitrate dehydrogenase protein 1 (IDH1) mutation and up to 2 dose levels of AG-221 in participants with an isocitrate dehydrogenase protein 2 (IDH2) mutation. AG-120 or AG-221 will be administered with 2 types of AML induction therapies (cytarabine with either daunorubicin or idarubicin) and 2 types of AML consolidation therapies (mitoxantrone with etoposide [ME] or cytarabine). After consolidation therapy, participants may continue on to maintenance therapy and receive daily treatment with single-agent AG-120 or AG-221 until relapse, development of an unacceptable toxicity, or hematopoietic stem cell transplant (HSCT). The study will end when all participants have discontinued study treatment.

Being tested
AG-120, AG-221, cytarabine, daunorubicin, idarubicin
Keywords
Acute Myeloid Leukemia, AML, Untreated AML, De novo AML, Secondary AML, Newly diagnosed AML, IDH1, IDH2, Induction therapy, Consolidation therapy, IDH
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

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

Study groups in NCT02632708
Study groupRoleWhat they receive
AG-120 with cytarabine and daunorubicinExperimentalDaily AG-120 administered orally in combination with standard Induction therapy and consolidation therapy. After 1 cycle of induction therapy, participants may undergo a second induction cycle given as per institutional practice. Participants who achieve an adequate response at the end of induction therapy will go on to receive consolidation therapy (mitoxantrone/etoposide or up to 4 cycles of cytarabine) in combination with AG-120. Participants who complete consolidation therapy and are in complete response (CR) or complete remission with incomplete hematologic recovery (CRi) (including CR with incomplete platelet recovery [CRp]) may continue on maintenance therapy and receive daily treatment with AG-120.
Receives: Drug: AG-120; Drug: cytarabine; Drug: daunorubicin; Drug: mitoxantrone; Drug: etoposide
AG-120 with cytarabine and idarubicinExperimentalDaily AG-120 administered orally in combination with standard Induction therapy and consolidation therapy. After 1 cycle of induction therapy, participants may undergo a second induction cycle given as per institutional practice. Participants who achieve an adequate response at the end of induction therapy will go on to receive consolidation therapy (mitoxantrone/etoposide or up to 4 cycles of cytarabine) in combination with AG-120. Participants who complete consolidation therapy and are in CR or CRi (including CRp) may continue on maintenance therapy and receive daily treatment with AG-120.
Receives: Drug: AG-120; Drug: cytarabine; Drug: idarubicin; Drug: mitoxantrone; Drug: etoposide
AG-221 with cytarabine and daunorubicinExperimentalDaily AG-221 administered orally in combination with standard Induction therapy and consolidation therapy. After 1 cycle of induction therapy, participants may undergo a second induction cycle given as per institutional practice. Participants who achieve an adequate response at the end of induction therapy will go on to receive consolidation therapy (mitoxantrone/etoposide or up to 4 cycles of cytarabine) in combination with AG-221. Participants who complete consolidation therapy and are in CR or CRi (including CRp) may continue on maintenance therapy and receive daily treatment with AG-221.
Receives: Drug: AG-221; Drug: cytarabine; Drug: daunorubicin; Drug: mitoxantrone; Drug: etoposide
AG-221 with cytarabine and idarubicinExperimentalDaily AG-221 administered orally in combination with standard Induction therapy and consolidation therapy. After 1 cycle of induction therapy, participants may undergo a second induction cycle given as per institutional practice. Participants who achieve an adequate response at the end of induction therapy will go on to receive consolidation therapy (mitoxantrone/etoposide or up to 4 cycles of cytarabine) in combination with AG-221. Participants who complete consolidation therapy and are in CR or CRi (including CRp) may continue on maintenance therapy and receive daily treatment with AG-221.
Receives: Drug: AG-221; Drug: cytarabine; Drug: idarubicin; Drug: mitoxantrone; Drug: etoposide
AG-221 (starting on Day 8) with cytarabine and daunorubicinExperimentalDaily AG-221 administered orally starting on Day 8 of induction cycle 1 in combination with standard Induction therapy and consolidation therapy. After 1 cycle of induction therapy, participants may undergo a second induction cycle given as per institutional practice. Participants who achieve an adequate response at the end of induction therapy will go on to receive consolidation therapy (mitoxantrone/etoposide or up to 4 cycles of cytarabine) in combination with AG-221. Participants who complete consolidation therapy and are in CR or CRi (including CRp) may continue on maintenance therapy and receive daily treatment with AG-221.
Receives: Drug: AG-221; Drug: cytarabine; Drug: daunorubicin; Drug: mitoxantrone; Drug: etoposide
AG-221 (starting on Day 8) with cytarabine and idarubicinExperimentalDaily AG-221 administered orally starting on Day 8 of induction cycle 1 in combination with standard Induction therapy and consolidation therapy. After 1 cycle of induction therapy, participants may undergo a second induction cycle given as per institutional practice. Participants who achieve an adequate response at the end of induction therapy will go on to receive consolidation therapy (mitoxantrone/etoposide or up to 4 cycles of cytarabine) in combination with AG-221. Participants who complete consolidation therapy and are in CR or CRi (including CRp) may continue on maintenance therapy and receive daily treatment with AG-221.
Receives: Drug: AG-221; Drug: cytarabine; Drug: idarubicin; Drug: mitoxantrone; Drug: etoposide

What is being measured

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

  1. Percentage of Participants with Adverse Events (AEs)

    An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related.

    Measured: Up to 26 weeks

Secondary outcomes (4)

  1. Recommended Phase 2 Dose (RP2D) of AG-120 and AG-221 when Administered with Induction and Consolidation Therapy

    Measured: Up to 26 weeks

  2. Pharmacokinetics (PK) of AG-120 and AG-221 in Plasma when Administered with Induction and Consolidation Therapy

    Descriptive statistics will be used to summarize PK parameters for each dose group and, where appropriate, for the entire population.

    Measured: Up to 26 weeks

  3. 2-hydroxyglutarate (2-HG) Levels in Plasma

    Measured: Up to 26 weeks

  4. Clinical Activity of AG-120 and AG-221 According to the 2003 Revised International Working Group (IWG) Criteria for AML

    Measured: Up to 26 weeks

Timeline

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

  1. First posted17 Dec 2015 (estimated)
  2. Study start31 Dec 2015
  3. Primary completion13 Dec 2018
  4. Study completion24 Jul 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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
153 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02632708
Sponsor's protocol ID
AG120-221-C-001
Other IDs
2015-004290-33, 2015
Status last verified
May 2026
First submitted
19 Nov 2015
Last updated
22 May 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

  • Stein EM, DiNardo CD, Fathi AT, Mims AS, Pratz KW, Savona MR, Stein AS, Stone RM, Winer ES, Seet CS, Dohner H, Pollyea DA, McCloskey JK, Odenike O, Lowenberg B, Ossenkoppele GJ, Patel PA, Roshal M, Frattini MG, Lersch F, Franovic A, Nabhan S, Fan B, Choe S, Wang H, Wu B, Hua L, Almon C, Cooper M, Kantarjian HM, Tallman MS. Ivosidenib or enasidenib combined with intensive chemotherapy in patients with newly diagnosed AML: a phase 1 study. Blood. 2021 Apr 1;137(13):1792-1803. doi: 10.1182/blood.2020007233.

    PubMed 33024987

  • Montesinos P, Fathi AT, de Botton S, Stein EM, Zeidan AM, Zhu Y, Prebet T, Vigil CE, Bluemmert I, Yu X, DiNardo CD. Differentiation syndrome associated with treatment with IDH2 inhibitor enasidenib: pooled analysis from clinical trials. Blood Adv. 2024 May 28;8(10):2509-2519. doi: 10.1182/bloodadvances.2023011914.

    PubMed 38507688

  • Fan B, Chen Y, Yin F, Hua L, Almon C, Nabhan S, Cooper M, Yang H, Hossain M. Pharmacokinetic/Pharmacodynamic Evaluation of Ivosidenib or Enasidenib Combined With Intensive Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed IDH1/2-Mutant Acute Myeloid Leukemia. Clin Pharmacol Drug Dev. 2022 Apr;11(4):429-441. doi: 10.1002/cpdd.1067. Epub 2022 Feb 14.

    PubMed 35166065

  • Shallis RM, Podoltsev NA. Maintenance therapy for acute myeloid leukemia: sustaining the pursuit for sustained remission. Curr Opin Hematol. 2021 Mar 1;28(2):110-121. doi: 10.1097/MOH.0000000000000637.

    PubMed 33394722

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AG-120, AG-221 and cytarabine in people with Newly Diagnosed Acute Myeloid Leukemia (AML) and Untreated AML, run by Institut de Recherches Internationales Servier at 17 sites in 3 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 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: under way, not looking for participants, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States, Netherlands, Germany. 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?

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?

Percentage of Participants with Adverse Events (AEs) (time frame: Up to 26 weeks). 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 NCT02632708, which also lists 4 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 22 May 2026.

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