AzTrials
AzTrials

Myelodysplastic SyndromesPhase 2NCT03503409

IDH1 (AG 120) Inhibitor in Patients With IDH1 Mutated Myelodysplastic Syndrome

A Phase 2 study testing AG-120 in people with Myelodysplastic Syndromes and Acute Myeloid Leukemia, run by Groupe Francophone des Myelodysplasies at 38 sites in 2 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

patients with MDS (Myelodysplastic Syndrome) and mutated IDH1 patients will be treated with AG120 (IDH1 inhibitor) 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
68 participants
Where
38 sitesin 2 countries
Study dates
14 May 2019to 2 Apr 2027
Phase
Phase 2
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

  • Patients must meet all of the following criteria to participate in the study:
  • Age ≥ 18 years
  • Myelodysplastic syndrome according to WHO classification including non-proliferative AML up to 29% of BM blast
  • Belonging to one of the following categories :
  • higher risk (IPSS high or int 2 ) MDS without response to azacitidine (CR,PR, stable disease with HI) after at least 6 cycles , or relapsing after a response but without overt progression (defined by at least doubling of marrow blasts, compared to pre azacitidine bone marrow, or AML progression beyond 30% blasts)
  • Untreated higher risk MDS (IPSS int-2, high) without life threatening cytopenia including ANC <500/mm3 or any recent severe infections and /or platelets below 30,000/mm3 or any bleeding symptom
Show all 20Show fewer
  • lower risk MDS with resistance or loss of response to a previous treatment with epoetin alpha/ beta (≥60000 U/w) or Darbopoetin (≥250 ug/w) given for at least 12 weeks and RBC transfusion requirement at least 2 U/8 weeks in the previous 16 weeks
  • Presence of IDH1 mutation in either blood or marrow prior to start of therapy;
  • Normal renal function, defined by creatinine less than 1.5 times the upper limit of normal, creatinine clearance (Modification of diet in renal disease) creatinine clearance ≥ 50 mL/min;
  • Normal liver function, defined by total bilirubin and transaminases less than 1.5 times the upper limit of normal;
  • Adequate cardiac ejection fraction (>40%);
  • Patient is not known to be refractory to platelet transfusions;
  • Written informed consent;
  • Patient must understand and voluntarily sign consent form.
  • Patient must be able to adhere to the visit schedule as outlined in the study and follow protocol requirements;
  • ECOG performance status 0-2 at the time of screening;
  • Female subjects with reproductive potential must have a negative serum pregnancy test within 7 days prior to the start of therapy. Subjects 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 (i.e., who have not menstruated at all) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 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 two highly effective forms of contraception from the time of giving informed consent, during the study and for 3 months (females and males) following the last dose of AG-120. A highly effective form of contraception is defined as hormonal oral contraceptives, injectables, patches, intrauterine devices.
  • Male patients must :
  • Agree the need for the use of a condom if engaged in sexual activity with a woman of childbearing potential during the entire period of treatment, even if disruption of treatment and during 3 months after end of treatment.
  • Agree to learn about the procedures for preservation of sperm before starting treatment

Who cannot join

  • A patient meeting any of the following criteria is not eligible to participate in the study:
  • Severe infection or any other uncontrolled severe condition.
  • Significant cardiac disease - NYHA Class III or IV or having suffered a myocardial infarction in the last 6 months.
  • Less than 14 days since prior treatment with growth factors (EPO, G-CSF).
  • Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before the study entry with the exception of hydroxyurea. The patient must have recovered from all acute toxicity from any previous therapy.
  • Subject has a heart-rate corrected QT interval using Fridericia's method (QTcF) ≥ 470 msec or any other factor that increases the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome). Subjects with prolonged QTcF interval in the setting of bundle branch block may participate in the study.
Show all 17Show fewer
  • Subject is taking known strong cytochrome P450 (CYP) 3A4 inducers or inhibitors or sensitive CYP3A4 substrate medications with a narrow therapeutic window, unless they can be transferred to other medications within ≥ 5 half-lives prior to dosing.
  • Subject is taking P-glycoprotein (P-gp) transporter-sensitive substrate medications with a narrow therapeutic window, unless they can be transferred to other medications within ≥ 5 half-lives prior to administration of study treatment
  • Active cancer or cancer during the year prior to trial entry other than basal cell carcinoma, or carcinoma in situ of the cervix or breast.
  • Patient already enrolled in another therapeutic trial of an investigational drug.
  • Known HIV infection or active hepatitis B or C.
  • Women who are or could become pregnant or who are currently breastfeeding.
  • Any medical or psychiatric contraindication that would prevent the patient from understanding and signing the informed consent form.
  • Patient eligible for allogeneic stem cell transplantation.
  • Known allergies to AG 120 or any of its excipients.
  • The study does not provide for the inclusion of persons referred to in Articles L. 1121-5 to L. 1121-9 and L. 1122-1-2 of the Public Health Code (e.g. minors, protected adults, etc.)
  • No affiliation to a health insurance system.

Trial locations and contacts

38 sites in 2 countries.

38 sites in 2 countries

France25 sites
  • CH Angers

    Angers, 49933

  • Centre Hospitalier de la Côte Basque

    Bayonne, 64109

  • Hôpital Nord Franche-Comté/Service de médecine interne / Hématologie clinique

    Belfort, 90015

  • CHU côte de Nacre

    Caen, 14033

  • CHU de Grenoble/Clinique Universitaire d'hématologie 6e A

    Grenoble, 38043

  • CH Le Mans/Service d'hématologie Oncologie

    Le Mans, 72000

  • CHRU de Limoges

    Limoges, 87046

  • centre hospitalier de Lyon

    Lyon, 69495

  • Institut Paoli Calmettes/Unité d'Hématologie 3

    Marseille, 13273

  • CHU Montpellier St Eloi

    Montpellier, 34295

  • Hôpital E. Muller-GHR Mulhouse Sud-Alsace

    Mulhouse, 68100

  • CHU Hôtel Dieu/Service d'Hématologie Clinique

    Nantes, 44093

  • Hôpital Archet 1/Service d'Hématologie Clinique

    Nice, 06200

  • GHU Caremeau

    Nîmes, 30029

  • Hôpital Saint Louis - Hématologie Séniors

    Paris, 75010

  • Hôpital Necker

    Paris, 75743

  • Hôpital Henri Mondor

    Paris, 94010

  • CHU de Haut-Lévèque/Centre François Magendie/Service des maladies du sang

    Pessac, 33604

  • CHU de Poitiers/Pôle de cancérologie - secteur tertiaire-

    Poitiers, 86021

  • Centre Henri Becquerel

    Rouen, 76038

  • institut de cancérologie Lucien Neuwirth

    Saint-Priest-en-Jarez, 42271

  • Médecine Interne/IUCT Oncopole

    Toulouse, 31059

  • CHU de Tours

    Tours, 37044

  • CHU Brabois

    Vandœuvre-lès-Nancy, 54511

  • Centre Hospitalier de Versailles-Hôpital André Mignot

    Versailles, 78157

Other trials in France

Italy13 sites
  • Ematologia ALESSANDRIA

    Alessandria, 16115121

  • CLINICA Ematologica ANCONA

    Ancona, 7160126

  • Ematologia BOLOGNA

    Bologna, 40138

  • Ematologia BRESCIA

    Brescia, 125123

  • Ematologia FIRENZE

    Florence, 350134

  • Clinica Ematologica Genova

    Genova, 1016132

  • Ematologia GENOVA

    Genova, 1016132

  • Ematologia LECCE

    Lecce, 73100

  • Ematologia MILANO

    Milan, 3520122

  • Ematologia ORBASSANO

    Orbassano, 1010043

  • Ematologia ed Immunologia Clinica PADOVA

    Padova, 235128

  • Reggio Calabria

    Reggio Calabria, 2189124

  • Ematologia ROMA

    Roma, 1000144

Other trials in Italy

About this study

Official title: A Single-arm Phase II Multicenter Study of IDH1 (AG 120) Inhibitor in Patients With IDH1 Mutated Myelodysplastic Syndrome

patients with MDS (Myelodysplastic Syndrome) and mutated IDH1 patients will be treated with AG120 (IDH1 inhibitor)

Read the detailed description

Myelodysplastic syndrome (MDS) are clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis leading to blood cytopenia, especially anemia, and often evolving to Acute myeloblastic Leukemia (AML). Main prognostic factors of MDS, for progression to AML and survival, include the number and importance of cytopenias, percent marrow blasts and bone marrow cytogenetic abnormalities. These factors are combined in an International Prognostic Scoring System (IPSS) that distinguishes 4 subgroups with significantly different risk of progression to AML and survival (low, intermediate 1 (int 1), intermediate 2 (int 2), high). Low and int 1 subgroups are often grouped together as "favorable " or low risk MDS, and int 2 and high subgroups are " unfavorable " or high risk MDS.

On the other hand, only 50 to 60% of the patients respond to Azacitidine, and most responders relapse within 12 to 15 months resulting in a median survival of only about 6 months in these patients,. As a result there is a need for new therapies in patients who fail to respond to azacitidine or decitabine and for whom there is currently no establish treatment.

Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are key metabolic enzymes that convert isocitrate to α-ketoglutarate. IDH1/2 mutations define distinct subsets of cancers, including low-grade gliomas and secondary glioblastomas, chondrosarcomas, intrahepatic chol- angiocarcinomas, and hematologic malignancies. Somatic point mutations in IDH1/2 confer a gain-of-function in cancer cells, resulting in the accumulation and secretion in vast excess of an oncometabolite, the D-2-hydroxyglutarate (D-2HG). Overproduction of D-2HG interferes with cellular metabolism and epigenetic regulation, contributing to oncogenesis. Indeed, high levels of D-2HG inhibit alpha-ketoglutarate-dependent dioxygenases, including histone and DNA demethylases, leading to histone and DNA hypermethylation and finally a block in cell differentiation.

preclinical studies have demonstrated that inhibition of IDH1/2-mutant enzymes decreases intracellular D-2-hydroxyglutarate (D-2HG) levels, reverses epigenetic dysregulation, and releases the differentiation block.

AG-120, a selective inhibitor of the IDH1 mutant enzyme Overall, in myeloid malignancies, AG120 have been mainly used in generally heavily pretreated AML, with about 40% of responses in patients with the respective IDH 1 mutation, and a median response duration exceeding 1 year when CR or PR was achieved.

Based on these results, we hypothesize that the IDH1 inhibitor (AG 120) may be an effective therapeutic option in patient with IDH1 mutation-positive myelodysplastic syndrome This is an open-label, single-arm multicenter, phase II study

The efficacy of AG 120 will be studied in 3 different groups of MDS patients with IDH-1 mutation:

  • Cohort A: Higher risk MDS without response (Complete response (CR), Partial Response (PR) ,stable disease with HI) after at least 6 cycles of azacitidine or relapse after a response
  • Cohort B: Untreated higher risk MDS without life threatening cytopenias (ie Absolute neutrophil count (ANC )< 500/mm3 or any recent infection, platelets below 30,000/mm3 or any bleeding symptom). Azacitidine will be added after 3 cycles of AG 120 in the absence of significant IWG 2006 criteria response
  • Cohort C: Lower risk MDS with anemia resistant to erythropoietic stimulating agents (primary or secondary resistance)
Being tested
AG-120
Medical subject headings
Myelodysplastic Syndromes, Leukemia, Myeloid, Acute

What participants receive

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

  • AG-120Drug

    500 mg/day Oral of AG-120. AG-120 will be dispensed on Day 1 of each treatment cycle

Study groups in NCT03503409
Study groupRoleWhat they receive
AG-120ExperimentalSubjects enrolled will receive continuous 28-day cycles of AG-120 - 500 mg. AG-120 will be dispensed on Day 1 of each treatment cycle
Receives: Drug: AG-120

What is being measured

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

  1. Overall hematological response

    overall hematological response

    Measured: 6 months

Secondary outcomes (2)
  1. response duration

    response duration

    Measured: 3 years

  2. IPSS progression

    time to IPSS progression

    Measured: 3 years

Timeline

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

  1. First posted19 Apr 2018
  2. Study start14 May 2019
  3. Primary completion2 Apr 2027 (estimated)
  4. Study completion2 Apr 2027 (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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Subjects enrolled will receive continuous 28-day cycles of AG-120. AG-120 will be dispensed on Day 1 of each treatment cycle
Masking
None (open label)
Enrolment
68 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03503409
Sponsor's protocol ID
IDIOME-STUDY
Status last verified
Aug 2026
First submitted
4 Apr 2018
Last updated
10 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Sebert M, Clappier E, Chevret S, Bergugnat H, Rauzy O, Stamatoullas A, Dimicoli-Salazar S, Selmi LAS, Chaffaut C, Chermat F, Larcher L, Goldwirt L, Thepot S, Peterlin P, Park S, Gourin MP, Vey N, Bally C, Maury S, Fossard G, D'Aveni M, Taksin AL, Cluzeau T, Fenaux P, Ades L. Ivosidenib monotherapy in IDH1 mutated myelodysplastic neoplasm/syndrome. Leukemia. 2026 Aug 25. doi: 10.1038/s41375-026-03100-3. Online ahead of print.

    PubMed 42642621
  • Greenberg PL, Stone RM, Abaza Y, Al-Kali A, Anand S, Ball B, Bennett JM, Borate U, Brunner AM, Chai-Ho W, Curtin P, DeZern AE, Gaensler K, Gahvari Z, Garcia-Manero G, Griffiths EA, Haque T, Jacoby M, Jonas BA, Keel S, Khanal R, Kishtagari A, Madanat Y, Maness LJ, McCurdy SR, McMahon C, Odenike O, Osman A, Reddy VV, Sallman DA, Sayar H, Shallis R, Singh A, Tanaka T, Thota S, Kovach E, Nguyen J, Hochstetler C. NCCN Guidelines(R) Insights: Myelodysplastic Syndromes, Version 2.2025. J Natl Compr Canc Netw. 2025 Mar;23(3):66-75. doi: 10.6004/jnccn.2025.0013.

    PubMed 40073835

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing AG-120 in people with Myelodysplastic Syndromes and Acute Myeloid Leukemia, run by Groupe Francophone des Myelodysplasies at 38 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 20 inclusion and 17 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 10 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 38 sites in France, Italy. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Overall hematological response (time frame: 6 months). 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 NCT03503409, which also lists 2 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 10 Aug 2026.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in