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

NCT02492737 | Completed Phase 1

• 1 other identifier: AG881-C-001
• Study Type: interventional
• Target: 46
• Locations: 2 countries
• Sites: 6

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

Conditions

Acute Myeloid Leukemia (AML); Myelodysplastic Syndrome; Hematologic Malignancies

Keywords

acute myeloid leukemia; AML; myelodysplastic syndrome; MDS; dual mutation; MPN; AITL; hematologic malignancies; IDH1; IDH2; AG-881

Outcome Measures

Primary Outcomes (2)

• Safety/tolerability; incidence of adverse events

  Up to 26 weeks, on average

• Maximum Tolerated Dose and/or the recommended Phase II dose of AG-881 in patients with advanced hematologic malignancies

  Up to 26 weeks, on average

Secondary Outcomes (4)

• Pharmacokinetics of AG-881 in patients with advanced hematologic malignancies

  Up to 26 weeks, on average

• Pharmacodynamic levels of AG-881

  Up to 26 weeks, on average

• Pharmacodynamic levels of 2-HG

  Up to 26 weeks, on average

• 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

  Up to 26 weeks, on average

Study Arms (1)

AG881

EXPERIMENTAL

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

Interventions

AG881 DRUG

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

AG881

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Agios Pharmaceuticals, Inc.: lead

Study Sites (6)

Unknown Facility

Aurora, Colorado, 80045, United States

Location

Unknown Facility

Chicago, Illinois, 60611, United States

Location

Unknown Facility

Boston, Massachusetts, 02215, United States

Location

Unknown Facility

New York, New York, 10065, United States

Location

Unknown Facility

Houston, Texas, 77030, United States

Location

Unknown Facility

Villejuif, 94800, France

Location

Related Publications (1)

• DiNardo CD, De Botton S, Pollyea DA, Stone RM, Altman JK, Fathi AT, Limsakun T, Liang M, Choe S, Hossain M, Tron AE, Meng Q, Kapsalis SM, Pandya SS, Stein EM. Safety, efficacy, and PK/PD of vorasidenib in previously treated patients with mIDH1/2 hematologic malignancies: A phase 1 study. Am J Hematol. 2023 Sep;98(9):E233-E236. doi: 10.1002/ajh.27005. Epub 2023 Jun 24. No abstract available.

  PMID: 37354069 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Neoplasms by Site

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2015
• First Posted: July 9, 2015
• Study Start: August 7, 2015
• Primary Completion: March 21, 2018
• Study Completion: March 21, 2018
• Last Updated: March 8, 2019

Record last verified: 2019-03

Locations

US (5); FR (1)