ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Orally Administered AG-881 in Patients With Advanced Hematologic Malignancies With an IDH1 and/or IDH2 Mutation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02492737
Recruitment Status : Completed
First Posted : July 9, 2015
Last Update Posted : June 26, 2018
Sponsor:
Information provided by (Responsible Party):
Agios Pharmaceuticals, Inc.

Brief Summary:
The purpose of this Phase I, multicenter study is to evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity of AG-881 in advanced hematologic malignancies that harbor an IDH1 and/or IDH2 mutation

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia (AML) Myelodysplastic Syndrome Hematologic Malignancies Drug: AG881 Phase 1

Detailed Description:
The first portion of the study is a dose escalation phase where cohorts of patients will receive ascending oral doses of AG-881 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 patients will receive AG-881 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 or the patient is removed at the discretion of the investigator.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 46 participants
Intervention Model: Single Group Assignment
Masking: None (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-881 in Patients With Advanced Hematologic Malignancies With an IDH1 and/or IDH2 Mutation
Actual Study Start Date : July 2015
Actual Primary Completion Date : April 27, 2018
Actual Study Completion Date : April 27, 2018


Arm Intervention/treatment
Experimental: AG881
AG-881 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Patients may continue treatment with AG-881 until disease progression, development of other unacceptable toxicity or Investigator discretion
Drug: AG881
AG-881 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Patients may continue treatment with AG-881 until disease progression or development of other unacceptable toxicity




Primary Outcome Measures :
  1. Safety/tolerability; incidence of adverse events [ Time Frame: Up to 26 weeks, on average ]
  2. Maximum Tolerated Dose and/or the recommended Phase II dose of AG-881 in patients with advanced hematologic malignancies [ Time Frame: Up to 26 weeks, on average ]

Secondary Outcome Measures :
  1. Pharmacokinetics of AG-881 in patients with advanced hematologic malignancies [ Time Frame: Up to 26 weeks, on average ]
  2. Pharmacodynamic levels of AG-881 [ Time Frame: Up to 26 weeks, on average ]
  3. Pharmacodynamic levels of 2-HG [ Time Frame: Up to 26 weeks, on average ]
  4. Clinical Activity according to the 2003 revised IWG criteria for AML, the 2006 modified IWG criteria for MDS, disease-specific response criteria for other hematologic malignancies [ Time Frame: Up to 26 weeks, on average ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients must be ≥18 years of age

Patients must have documented IDH1 and/or IDH2 gene-mutated disease

Patients must have an advanced hematologic malignancy with an IDH1 and/or IDH2 mutation

Patient must be able to understand and willing to sign an informed consent

Patients must have ECOG PS of 0 to 2

Patients must have adequate hepatic function as evidenced by serum total bilirubin ≤1.5 upper limit of normal (ULN), unless considered due to Gilbert's disease or leukemic involvement

Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤3.0 × ULN, unless considered due to involvement by the neoplasm under consideration for treatment

Patients must have adequate renal function as evidenced by a serum creatinine ≤2.0 × ULN or Creatinine clearance 40 mL/min based on the Cockroft-Gault glomerular filtration rate (GFR) estimation

Patients must be recovered from any clinically relevant toxic effects of any prior surgery, radiotherapy, or other therapy intended for the treatment of cancer

Female patients with reproductive potential must have a negative serum pregnancy test within 7 days prior to the start of therapy. Patients with reproductive potential are defined as sexually mature women who have not undergone a hysterectomy, bilateral oophorectomy or tubal occlusion or who have not been naturally postmenopausal (i.e., who have not menstruated at all) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)

Exclusion Criteria:

Patients who have undergone HSCT within 60 days

Patients who received systemic anticancer therapy or radiotherapy <14 days prior to their first day of study drug administration

Patients who received an investigational agent <14 days prior

Patients who are pregnant or breast feeding

Patients with an active severe infection who require anti-infective therapy 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, patients with tumor fever may be enrolled)

Patients 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

Patients with a history of myocardial infarction within the last 6 months

Patients with known unstable or uncontrolled angina pectoris

Patients with a known history of severe and/or uncontrolled ventricular arrhythmias

Patients with QTc interval ≥450 msec or with other factors that increase the risk of QT prolongation or arrhythmic events

Patients taking medications that are known to prolong the QT interval

Patients with known infection with human immunodeficiency virus (HIV) or active hepatitis B or C

Patients 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

Patients with immediately life-threatening, severe complications of hematologic malignancies such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02492737


Locations
United States, Colorado
Aurora, Colorado, United States, 80045
United States, Illinois
Chicago, Illinois, United States, 60611
United States, Massachusetts
Boston, Massachusetts, United States, 02215
United States, New York
New York, New York, United States, 10065
United States, Texas
Houston, Texas, United States, 77030
France
Villejuif, France, 94800
Sponsors and Collaborators
Agios Pharmaceuticals, Inc.

Responsible Party: Agios Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02492737     History of Changes
Other Study ID Numbers: AG881-C-001
First Posted: July 9, 2015    Key Record Dates
Last Update Posted: June 26, 2018
Last Verified: June 2018

Keywords provided by Agios Pharmaceuticals, Inc.:
acute myeloid leukemia
AML
myelodysplastic syndrome
MDS
dual mutation
MPN
AITL
hematologic malignancies
IDH1
IDH2
AG-881

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms
Myelodysplastic Syndromes
Preleukemia
Leukemia
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions