A Study to Assess the Safety and Efficacy of Two Combinations of Isocitrate Dehydrogenase (IDH) Mutant Targeted Therapies Plus Azacitidine in Participants With Newly Diagnosed Acute Myeloid Leukemia (AML) Harboring IDH Mutations Who Are Not Candidates to Receive Intensive Induction Chemotherapy

Condition(s) studied

Investigational drug(s) / intervention(s)

AG-120: Specified dose on specified days

Azacitidine: Specified dose on specified days

AG-221: Specified dose on specified days

Study summary

The purpose of this study are

1. to determine the recommended combination dose of AG-120 and AG-221 separately when administered with azacitidine and,
2. to investigate the safety, tolerability, and efficacy of the combinations of AG-120 with azacitidine and AG-221 with azacitidine versus with azacitidine alone in participants with acute myeloid leukemia (AML) with the isocitrate dehydrogenase (IDH) enzyme isoforms 1 or 2 mutations, respectively.

Eligibility

Primary outcome measure(s)

• The Number of Participants Experiencing Dose-limiting Toxicities (DLTs): Phase 1B (Dose Finding Stage) — From first dose to 28 days after first dose
  Dose-limiting toxicities (DLTs) are defined as an event that constitute a change from baseline irrespective of outcome and determined by the investigator to be related to treatment. The DLT-evaluable participants were defined as participants who took at least 1 dose of study drug in the Phase 1b Dose-Finding Stage and either had a DLT during Cycle 1 (regardless of amount of study drug exposure), or had no DLT and completed at least 75% of AG-120 or AG-221 doses (21 out of 28 days) and a minimum of 5 doses of AZA, at least 50% of the planned combination doses for AG-120 or AG-221 and AZA administered together (in the same day for 4 out of 7 days) in the first 28 days from C1D1, and were also considered by the Clinical Study Team to have sufficient safety data available to conclude that a DLT did not occur during Cycle 1.
• The Number of Participants Experiencing Adverse Events: Phase 1B (Dose Finding and Expansion Stage) — From first dose to 28 days after last dose (up to approximately 13 months)
  The number of participants experiencing different types of adverse events (AE). An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A Serious Adverse Event (SAE) is any AE occurring at any dose that: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, and/or constitutes an important medical event. Adverse events were analyzed in terms of treatment-emergent AEs (TEAEs). Treatment-emergent adverse events (TEAE) was defined as events that began on or after the start of study drug through 28 days after the last study treatment. The severity/intensity of AEs were graded based upon the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.03) where Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death.
• Overall Response Rate: Phase 2 (Randomized Stage) — From first dose up to approximately 26 months
  The percent of participants with MLFS + CR + CRi + CRp + PR according to modified International Working Group Acute Myeloid Leukemia (IWG AML) response criteria as assessed by investigator. Complete response (CR) and morphologic leukemia-free state (MLFS) are defined as \<5% blasts in a BM aspirate sample with marrow spicules and a count of ≥200 nucleated cells. There should be no blasts with Auer rods and no extramedullary disease. CR must also include: absolute neutrophil count (ANC) ≥1,000/μL, Platelet count ≥100,000/μL, and independent of red cell transfusions for ≥1 week before each response assessment. Complete remission with incomplete neutrophil recovery (CRi) is all criteria of CR except ANC. Complete remission with incomplete platelet recovery (CRp) is all criteria of CR except platelet count. Partial remission (PR) is defined as all hematologic criteria of CR with a \>50% decrease in the percentage of BM blasts to 5% to 25%. (\<5% considered if Auer rods are present).

Trial sites (49)

+ 9 more sites — see the full list on the official registry below.

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