Skip to main content

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

Trial Status: Active

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.

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.

Alabama

Birmingham
University of Alabama at Birmingham Cancer Center
Status: CLOSED_TO_ACCRUAL

Arizona

Scottsdale
Mayo Clinic in Arizona
Status: ACTIVE

California

Duarte
City of Hope Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL
Los Angeles
UCLA / Jonsson Comprehensive Cancer Center
Status: ACTIVE
San Francisco
UCSF Medical Center-Mount Zion
Status: CLOSED_TO_ACCRUAL

Colorado

Aurora
University of Colorado Hospital
Status: CLOSED_TO_ACCRUAL_AND_INTERVENTION

Florida

Jacksonville
Mayo Clinic in Florida
Status: ACTIVE

Georgia

Atlanta
Emory University Hospital / Winship Cancer Institute
Status: CLOSED_TO_ACCRUAL

Illinois

Chicago
Northwestern University
Status: CLOSED_TO_ACCRUAL

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: ACTIVE
Contact: Gabrielle Tova Prince
Phone: 410-955-8804

Massachusetts

Boston
Brigham and Women's Hospital
Status: ACTIVE
Dana-Farber Cancer Institute
Status: ACTIVE
Massachusetts General Hospital Cancer Center
Status: ACTIVE

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: ACTIVE

New York

New York
Memorial Sloan Kettering Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Eytan M. Stein
Phone: 212-639-3314

Ohio

Cleveland
Case Comprehensive Cancer Center
Status: ADMINISTRATIVELY_COMPLETE
Columbus
Ohio State University Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL

Oregon

Portland
OHSU Knight Cancer Institute
Status: CLOSED_TO_ACCRUAL
Contact: Elie Traer
Phone: 503-494-1080

South Carolina

Charleston
Medical University of South Carolina
Status: CLOSED_TO_ACCRUAL

Texas

Dallas
UT Southwestern / Simmons Cancer Center-Dallas
Status: ACTIVE
Houston
M D Anderson Cancer Center
Status: CLOSED_TO_ACCRUAL

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Agios Pharmaceuticals

  • Primary ID AG120-C-001
  • Secondary IDs NCI-2014-00720
  • Clinicaltrials.gov ID NCT02074839