Recruiting
Phase 1

AG-120

Sponsor:

Institut de Recherches Internationales Servier

Code:

NCT02074839

Conditions

Relapsed or Refractory Acute Myeloid Leukemia (AML)

Untreated AML

Other IDH1-mutated Positive Hematologic Malignancies

Myelodysplastic Syndromes

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

AG-120

Study Details

Brief 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. 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.

Conditions

Relapsed or Refractory Acute Myeloid Leukemia (AML)

Untreated AML

Other IDH1-mutated Positive Hematologic Malignancies

Myelodysplastic Syndromes

Study ID

NCT02074839

Start date

Mar 1, 2014

Status verified date

Jun, 2026

Completion date

Dec 31, 2026

Anticipated

Primary completion date

Dec 31, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Key Inclusion Criteria:

  • 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
  • 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.

Key Exclusion Criteria:

  • 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.
  • 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.

Study Design

Enrollment

291 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: AG-120

AG-120 administered continuously as a single agent dosed orally every day of a 28-day cycle.

Interventions

AG-120

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.

Primary outcome measure

  • Safety/tolerability: incidence of adverse events. [ Time Frame: up to 26 weeks, on average ]
  • Maximum Tolerated Dose and/or the recommended Phase II dose of AG-120 in subjects with advanced hematologic malignancies. [ Time Frame: up to 26 weeks, on average ]
  • Assess clinical activity of AG-120 in subjects with relapsed or refractory AML who are enrolled in the Expansion Phase. [ Time Frame: up to 26 weeks, on average ]
  • Safety/tolerability of treatment with AG-120 in subjects with relapsed or refractory myelodysplastic syndrome. [ Time Frame: up to 26 weeks, on average ]
  • Assess clinical activity of AG-120 in subjects with relapsed or refractory myelodysplastic syndrome. [ Time Frame: up to 26 weeks, on average ]

Central Contacts and Locations

Central contacts

Institut de Recherches Internationales Servier Clinical Studies Department

+33 1 55 72 43 66scientificinformation@servier.com

Locations

Medical University of South Carolina

Recruiting

Charleston, South Carolina, United States, 29425

UT Southwestern Medical Center

Recruiting

Dallas, Texas, United States, 75390

MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

More Information

Sponsor

Institut de Recherches Internationales Servier

Last update posted

Jun 15, 2026

Last verified

Jun, 2026

Keywords

  • acute myeloid leukemia
  • AML
  • myelodysplastic syndrome
  • MDS
  • hematologic malignancies
  • IDH
  • Untreated AML
  • IDH1
  • relapsed AML
  • refractory AML

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Institut de Recherches Internationales Servier on 2026-06-15.