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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2015 by Agios Pharmaceuticals, Inc.
Sponsor:
Information provided by (Responsible Party):
Agios Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT02074839
First received: February 21, 2014
Last updated: July 6, 2015
Last verified: July 2015
  Purpose

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 three cohorts of patients will receive AG-120 to further evaluate the safety, tolerability, and clinical activity of the recommended Phase II dose. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.


Condition Intervention Phase
Relapsed or Refractory Acute Myeloid Leukemia (AML)
Untreated AML
Other IDH1-mutated Positive Hematologic Malignancies
Drug: AG-120
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Agios Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Safety/tolerability: incidence of adverse events [ Time Frame: up to 26 weeks, on average ] [ Designated as safety issue: Yes ]
  • Maximum Tolerated Dose and/or the recommended Phase II dose of AG-120 in subjects with advanced hematologic malignancies [ Time Frame: up to 26 weeks, on average ] [ Designated as safety issue: Yes ]
  • Assess clinical activity of AG-120 in subjects with relapsed or refractory AML who are enrolled in the Expansion Phase [ Time Frame: up to 26 weeks, on average ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Dose Limiting Toxicities of AG-120 in subjects with advanced hematologic malignancies [ Time Frame: up to 26 weeks, on average ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics of AG-120 in subjects with advanced hematologic malignancies [ Time Frame: up to 26 weeks, on average ] [ Designated as safety issue: Yes ]
    Descriptive statistics will be used to summarize PK parameters for each dose group and, where appropriate, for the entire population. Such parameters will include (but are not limited to) maximum concentration (Cmax), time to maximum concentration (Tmax), AUC, elimination half-life, and the fraction of drug excreted unchanged in the urine.

  • Pharmacodynamic relationship of AG-120 and 2-HG [ Time Frame: up to 26 weeks, on average ] [ Designated as safety issue: Yes ]
    The potential relationship between plasma exposure of AG-120 and plasma, urine, or bone marrow 2-HG levels will be explored with descriptive and graphical methods.

  • Clinical Activity of AG-120 in advanced hematologic malignancies according to the 2003 revised IWG criteria for AML or the 2006 modified IWG criteria for MDS or MDS/myeloproliferative neoplasms (MPN) [ Time Frame: up to 26 weeks, on average ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 211
Study Start Date: March 2014
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AG-120
AG-120 administered continuously as a single agent dosed orally every day of a 28-day cycle.
Drug: 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Subject must be ≥18 years of age.
  • Subjects must have documented IDH1 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 (QTcF) 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02074839

Contacts
Contact: Molly Prahl, RN 617.649.8635 molly.prahl@agios.com
Contact: Sam Agresta, MD, MPH & TM 617.649.8621 sam.agresta@agios.com

Locations
United States, Alabama
Not yet recruiting
Birmingham, Alabama, United States, 35294
United States, Arizona
Not yet recruiting
Phoenix, Arizona, United States, 85259
United States, California
Not yet recruiting
Duarte, California, United States, 91010
Not yet recruiting
San Francisco, California, United States, 94143
United States, Colorado
Recruiting
Aurora, Colorado, United States, 80045
United States, Florida
Not yet recruiting
Jacksonville, Florida, United States, 32224
Recruiting
Miami, Florida, United States, 33136
United States, Georgia
Not yet recruiting
Atlanta, Georgia, United States, 30322
United States, Illinois
Recruiting
Chicago, Illinois, United States, 60611
United States, Maryland
Not yet recruiting
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Recruiting
Boston, Massachusetts, United States, 02215
United States, Missouri
Not yet recruiting
Saint Louis, Missouri, United States, 63110
United States, New York
Recruiting
New York, New York, United States, 10065
United States, Ohio
Not yet recruiting
Cleveland, Ohio, United States, 44124
Not yet recruiting
Columbus, Ohio, United States, 43210
United States, Tennessee
Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
Recruiting
Dallas, Texas, United States, 75390
Recruiting
Houston, Texas, United States, 77030
France
Recruiting
Villejuif, France, 94800
Sponsors and Collaborators
Agios Pharmaceuticals, Inc.
Investigators
Study Director: Clinical Development Agios Pharmaceuticals, Inc.
  More Information

No publications provided

Responsible Party: Agios Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02074839     History of Changes
Other Study ID Numbers: AG120-C-001
Study First Received: February 21, 2014
Last Updated: July 6, 2015
Health Authority: United States: Food and Drug Administration
France: Agence Nationale de Sécurité du Médicament et des Produits de Santé (ANSM)

Keywords provided by Agios Pharmaceuticals, Inc.:
acute myeloid leukemia
AML
myelodysplastic syndrome
MDS
hematologic malignancies
IDH
Untreated AML
IDH1
relapsed AML
refractory AML

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms
Leukemia
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on July 30, 2015