Acute Myeloid Leukemia Clinical Trial

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

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.

View Eligibility Criteria

Eligibility Criteria

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 is for people with:

Acute Myeloid Leukemia

Phase:

Phase 1

Estimated Enrollment:

291

Study ID:

NCT02074839

Recruitment Status:

Recruiting

Sponsor:

Institut de Recherches Internationales Servier

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There are 28 Locations for this study

See Locations Near You

University of Alabama at Birmingham
Birmingham Alabama, 35294, United States
Mayo Clinic-AZ
Phoenix Arizona, 85259, United States
City of Hope
Duarte California, 91010, United States
University of California-Los Angeles
Los Angeles California, 90095, United States
University of California-San Francisco
San Francisco California, 94143, United States
University of Colorado Denver
Aurora Colorado, 80045, United States
Mayo Clinic-Jacksonville
Jacksonville Florida, 32224, United States
University of Miami
Miami Florida, 33136, United States
Emory University
Atlanta Georgia, 30322, United States
Northwestern University Medical Hospital
Chicago Illinois, 60611, United States
John Hopkins Cancer Center
Baltimore Maryland, 21287, United States
Massachusetts General Hospital
Boston Massachusetts, 02214, United States
Dana Farber Cancer Institute
Boston Massachusetts, 02215, United States
Karmanos Cancer Center
Detroit Michigan, 48201, United States
Washington University
Saint Louis Missouri, 63110, United States
Memorial Sloan Kettering Cancer Center
New York New York, 10021, United States
Cornell Cancer Center
New York New York, 10065, United States
Duke Cancer Center
Durham North Carolina, 27705, United States
Cleveland Clinic
Cleveland Ohio, 44124, United States
Ohio State University
Columbus Ohio, 43210, United States
Oregon Health and Science University
Portland Oregon, 97239, United States
Medical University of South Carolina
Charleston South Carolina, 29425, United States
Sarah Cannon Research Institute
Nashville Tennessee, 37203, United States
UT Southwestern Medical Center
Dallas Texas, 75390, United States
MD Anderson Cancer Center
Houston Texas, 77030, United States
Hopital La Timone
Marseille , , France
Hopital Haut-Leveque
Pessac , 33600, France
Central Lyon Sud
Pierre-Bénite , 69310, France
Institute Gustave Roussly (IGR)
Villejuif , 94800, France

How clear is this clinincal trial information?

Study is for people with:

Acute Myeloid Leukemia

Phase:

Phase 1

Estimated Enrollment:

291

Study ID:

NCT02074839

Recruitment Status:

Recruiting

Sponsor:


Institut de Recherches Internationales Servier

How clear is this clinincal trial information?

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