Clinical Trial: Study of Orally Administered AG-221 in Subjects With Advanced Solid Tumors, Including Glioma, and With Angioimmunoblastic T-cell Lymphoma, With an IDH2 Mutation Subjects With Advanced Solid Tumors, Including Glioma, and With Angioimmunoblastic T-cell Lymphoma, With an IDH2 Mutation

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase 1/2, Multicenter, Open-Label, Dose-Escalation Study of AG-221 in Subjects With Advanced Solid Tumors, Including Glioma, and With Angioimmunoblastic T-cell Lymphoma

Brief Summary: The purpose of this Phase 1/2, multi-center study is to evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity of AG-221 in subjects with advanced solid tumors, including glioma, and with angioimmunoblastic T-cell lymphoma (AITL), with an IDH2 mutation. The first portion of the study is a dose escalation phase where cohorts of patients will receive ascending oral doses of AG-221 to determine maximum tolerated dose (MTD) and/or the recommended Phase 2 dose. The second portion of the study is a planned dose expansion phase where three cohorts of patients will receive AG-221 to further evaluate the safety, tolerability, and clinical activity. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

Detailed Summary:
Sponsor: Celgene

Current Primary Outcome:

  • Safety/tolerability: incidence of adverse events [ Time Frame: up to 26 weeks, on average ]
  • Maximum Tolerated Dose and/or the recommended Phase II dose of AG-221 in subjects with advanced solid tumors, including glioma, and AITL [ Time Frame: up to 26 weeks, on average ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Identification and Description of Dose Limiting Toxicities associated with AG-221 in subjects with advanced solid tumors, including glioma, and with AITL [ Time Frame: up to 26 weeks, on average ]
  • Pharmacokinetic profiles including max concentration (Cmax), time to maximum concentration (Tmax), AUC, and elimination half-life [ Time Frame: up to 26 weeks, on average ]
    Descriptive statistics will be used to summarize PK profile parameters for each dose group and, where appropriate, for the entire population
  • Pharmacodynamic relationship between levels of AG-221 and 2-HG [ Time Frame: up to 26 weeks, on average ]
    Descriptive and graphical methods will be used to explore the potential relationship between levels of AG-221 and 2-HG levels
  • Clinical Activity according to RECIST v1.1 (2009), RANO (2010), and IWG for malignant lymphoma (2007) [ Time Frame: up to 26 weeks, on average ]
    Clinical activity will be assessed based on RECIST v1.1 for subjects with solid tumors without glioma, by modified RANO criteria for subjects with glioma, or by the revised IWG criteria for subjects with AITL


Original Secondary Outcome: Same as current

Information By: Celgene

Dates:
Date Received: October 16, 2014
Date Started: October 24, 2014
Date Completion:
Last Updated: May 10, 2017
Last Verified: May 2017