RECRUITING

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

Conditions

Relapsed or Refractory Acute Myeloid Leukemia (AML)Untreated AML Other IDH1-mutated Positive Hematologic Malignancies Myelodysplastic Syndromes acute myeloid leukemia AML myelodysplastic syndrome MDS hematologic malignancies IDH IDH1 relapsed AML refractory AML

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Phase I, Multicenter, Open-Label, Dose-Escalation and Expansion, Safety, Pharmacokinetic, Pharmacodynamic, and Clinical Activity Study of Orally Administered AG-120 in Subjects With Advanced Hematologic Malignancies With an IDH1 Mutation

Quick Facts

Study Start:2014-03

Study Completion:2025-08

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT02074839

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.	* 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.

Inclusion Criteria

Exclusion 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.

* 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.

Contacts and Locations

Study Contact

Institut de Recherches Internationales Servier Clinical Studies Department

CONTACT

+33 1 55 72 43 66

scientificinformation@servier.com

Study Locations (Sites)

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

Moffit Cancer Center

Tampa, Florida, 33612

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

Collaborators and Investigators

Sponsor: Institut de Recherches Internationales Servier

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2014-03

Study Completion Date2025-08

Study Record Updates

Study Start Date2014-03

Study Completion Date2025-08

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

Relapsed or Refractory Acute Myeloid Leukemia (AML)
Untreated AML
Other IDH1-mutated Positive Hematologic Malignancies
Myelodysplastic Syndromes