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

NCT ID: NCT02074839

Last Updated: 2025-06-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 291 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-01
• Study Completion Date: 2026-03-31

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 Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AG-120

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

Group Type: EXPERIMENTAL

AG-120

Intervention Type: DRUG

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.

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.

Intervention Type: DRUG

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institut de Recherches Internationales Servier

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status: ACTIVE_NOT_RECRUITING

Mayo Clinic-AZ

Phoenix, Arizona, United States

Site Status: TERMINATED

City of Hope

Duarte, California, United States

Site Status: ACTIVE_NOT_RECRUITING

University of California-Los Angeles

Los Angeles, California, United States

Site Status: TERMINATED

University of California-San Francisco

San Francisco, California, United States

Site Status: TERMINATED

University of Colorado Denver

Aurora, Colorado, United States

Site Status: TERMINATED

Mayo Clinic-Jacksonville

Jacksonville, Florida, United States

Site Status: TERMINATED

University of Miami

Miami, Florida, United States

Site Status: TERMINATED

Moffit Cancer Center

Tampa, Florida, United States

Site Status: ACTIVE_NOT_RECRUITING

Emory University

Atlanta, Georgia, United States

Site Status: ACTIVE_NOT_RECRUITING

Northwestern University Medical Hospital

Chicago, Illinois, United States

Site Status: TERMINATED

John Hopkins Cancer Center

Baltimore, Maryland, United States

Site Status: ACTIVE_NOT_RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status: TERMINATED

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status: TERMINATED

Karmanos Cancer Center

Detroit, Michigan, United States

Site Status: TERMINATED

Washington University

St Louis, Missouri, United States

Site Status: TERMINATED

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status: ACTIVE_NOT_RECRUITING

Cornell Cancer Center

New York, New York, United States

Site Status: TERMINATED

Duke Cancer Center

Durham, North Carolina, United States

Site Status: TERMINATED

Cleveland Clinic

Cleveland, Ohio, United States

Site Status: WITHDRAWN

Ohio State University

Columbus, Ohio, United States

Site Status: TERMINATED

Oregon Health and Science University

Portland, Oregon, United States

Site Status: TERMINATED

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status: RECRUITING

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status: TERMINATED

UT Southwestern Medical Center

Dallas, Texas, United States

Site Status: RECRUITING

MD Anderson Cancer Center

Houston, Texas, United States

Site Status: RECRUITING

Hopital La Timone

Marseille, , France

Site Status: TERMINATED

Hopital Haut-Leveque

Pessac, , France

Site Status: RECRUITING

Central Lyon Sud

Pierre-Bénite, , France

Site Status: RECRUITING

Institute Gustave Roussly (IGR)

Villejuif, , France

Site Status: RECRUITING

Countries

United States; France

Central Contacts

Institut de Recherches Internationales Servier Clinical Studies Department

Role: CONTACT

scientificinformation@servier.com

+33 1 55 72 43 66

References

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Reference Type: BACKGROUND

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Reference Type: DERIVED

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Reference Type: DERIVED

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Reference Type: DERIVED

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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.

Reference Type: DERIVED

PMID: 31841594 (View on PubMed)

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.

Reference Type: DERIVED

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Reference Type: DERIVED

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Study Documents

Document Type: Individual Participant Data Set

View Document

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Document Type: Clinical Study Report

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Document Type: Study-level clinical trial data

View Document

Other Identifiers

AG120-C-001

Identifier Type: -

Identifier Source: org_study_id