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Protocol # 14-035

Status

Recruiting

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.

Condition

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

Interventions

  • AG-120

Phase

Phase 1

Study Type

Interventional

Further Study Details

Primary Outcome:

  • Safety/tolerability: incidence of adverse events.
  • Maximum Tolerated Dose and/or the recommended Phase II dose of AG-120 in subjects with advanced hematologic malignancies.
  • Assess clinical activity of AG-120 in subjects with relapsed or refractory AML who are enrolled in the Expansion Phase.
  • Safety/tolerability of treatment with AG-120 in subjects with relapsed or refractory myelodysplastic syndrome.
  • Assess clinical activity of AG-120 in subjects with relapsed or refractory myelodysplastic syndrome.

Secondary Outcome:

  • Dose Limiting Toxicities of AG-120 in subjects with advanced hematologic malignancies.
  • Pharmacokinetics of AG-120 in subjects with advanced hematologic malignancies.
  • Pharmacodynamic relationship of AG-120 and 2-HG.
  • 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).
  • Serial blood sampling at specified time points for determination of plasma concentration-time profiles and PK parameters (Cmax) of AG-120 in subjects with R/R MDS.
  • Serial blood sampling at specified time points for determination of plasma concentration-time profiles and PK parameters (Tmax) of AG-120 in subjects with R/R MDS.
  • Serial blood sampling at specified time points for determination of plasma concentration-time profiles and PK parameters (AUC) of AG-120 in subjects with R/R MDS.
  • Blood and bone marrow sampling at specified time points for determination of 2-HG levels to characterize the percent of 2-HG inhibition of AG-120 in plasma and bone marrow.

Enrollment

291

Study Start Date

March 2014

Eligibility

  • Gender:     All
  • Minimum age:     18 Years
  • Maximum age:     N/A
  • Healthy volunteers:     No

Sponsors

Institut de Recherches Internationales Servier

Source

Servier

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

Clinicaltrials.gov Identifier

NCT02074839

     

Source: Clinicaltrials.gov. Through our founding membership in the Dana-Farber/Harvard Cancer Center, an NCI-designated Comprehensive Cancer Center, these clinical trials are conducted at the Massachusetts General Hospital Cancer Center and may be available at other partner institutions.