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Recruiting Phase 1

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

NCT02074839 · tracked via the Priya Life Science France tracker
Phase
Phase 1
Started
2014-03-01
Last updated
2026-06-15

Condition(s) studied

Relapsed or Refractory Acute Myeloid Leukemia (AML)Untreated AMLOther IDH1-mutated Positive Hematologic MalignanciesMyelodysplastic Syndromes

Investigational drug(s) / intervention(s)

AG-120 →

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.

Study 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.

Eligibility

Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.

Primary outcome measure(s)

  • Safety/tolerability: incidence of adverse events. — 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. — 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. — up to 26 weeks, on average
  • Safety/tolerability of treatment with AG-120 in subjects with relapsed or refractory myelodysplastic syndrome. — up to 26 weeks, on average
  • Assess clinical activity of AG-120 in subjects with relapsed or refractory myelodysplastic syndrome. — up to 26 weeks, on average

Trial sites (30)

FacilityCityRegionStatus
University of Alabama at Birmingham Birmingham Alabama Active Not Recruiting
Mayo Clinic-AZ Phoenix Arizona Terminated
City of Hope Duarte California Active Not Recruiting
University of California-Los Angeles Los Angeles California Terminated
University of California-San Francisco San Francisco California Terminated
University of Colorado Denver Aurora Colorado Terminated
Mayo Clinic-Jacksonville Jacksonville Florida Terminated
University of Miami Miami Florida Terminated
Moffit Cancer Center Tampa Florida Active Not Recruiting
Emory University Atlanta Georgia Active Not Recruiting
Northwestern University Medical Hospital Chicago Illinois Terminated
John Hopkins Cancer Center Baltimore Maryland Active Not Recruiting
Massachusetts General Hospital Boston Massachusetts Terminated
Dana Farber Cancer Institute Boston Massachusetts Terminated
Karmanos Cancer Center Detroit Michigan Terminated
Washington University St Louis Missouri Terminated
Memorial Sloan Kettering Cancer Center New York New York Active Not Recruiting
Cornell Cancer Center New York New York Terminated
Duke Cancer Center Durham North Carolina Terminated
Cleveland Clinic Cleveland Ohio Withdrawn
Ohio State University Columbus Ohio Terminated
Oregon Health and Science University Portland Oregon Terminated
Medical University of South Carolina Charleston South Carolina Recruiting
Sarah Cannon Research Institute Nashville Tennessee Terminated
UT Southwestern Medical Center Dallas Texas Recruiting
MD Anderson Cancer Center Houston Texas Recruiting
Hopital La Timone Marseille France Terminated
Hopital Haut-Leveque Pessac France Recruiting
Central Lyon Sud Pierre-Bénite France Recruiting
Institute Gustave Roussly (IGR) Villejuif France Recruiting
Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT02074839 on ClinicalTrials.gov ↗ ← All trials in France