Study of AG-120 (Ivosidenib) vs. Placebo in Combination With Azacitidine in Patients With Previously Untreated Acute Myeloid Leukemia With an IDH1 Mutation

Official Title

A Phase 3, Multicentre, Double-Blind, Randomized, Placebo-Controlled Study of AG-120 in Combination With Azacitidine in Subjects ≥ 18 Years of Age With Previously Untreated Acute Myeloid Leukemia With an IDH1 Mutation

Summary:

Study AG120-C-009 is a global, Phase 3, multicentre, double-blind, randomized, placebo-controlled clinical trial to evaluate the efficacy and safety of AG-120 (ivosidenib) + azacitidine vs placebo + azacitidine in adult participants with previously untreated IDH1m AML who are considered appropriate candidates for non-intensive therapy. The primary endpoint is event-free survival (EFS). The key secondary efficacy endpoints are overall survival (OS), rate of complete remission (CR), rate of CR and complete remission with partial hematologic recovery (CRh), and overall response rate (ORR). Participants eligible for study treatment based on Screening assessments will be randomized 1:1 to receive oral AG-120 or matched placebo, both administered in combination with subcutaneous (SC) or intravenous (IV) azacitidine. An estimated 200 participants will take part in the study.

Trial Description

Primary Outcome:

• Event-Free Survival (EFS)

• Complete Remission Rate (CR Rate)
• Overall Survival (OS)
• CR + Complete Remission With Partial Hematologic (CRh) Rate
• Objective Response Rate (ORR)
• CR + CRi (Including CRp) Rate
• Duration of CR (DOCR)
• Duration of CRh (DOCRh)
• Duration of Response (DOR)
• Duration of CRi (DOCRi)
• Time to CR (TTCR)
• Time to CRh (TTCRh)
• Time to Response (TTR)
• Time to CRi (TTCRi)
• Percentage of Participants with Abnormalities in Vital Sign Measurements
• Percentage of Participants with Abnormalities in Eastern Cooperative Oncology Group Performance Status (ECOG PS)
• Percentage of Participants with Abnormalities in 12-lead Electrocardiograms (ECGs)
• Percentage of Participants with Abnormalities in Echocardiogram (ECHO) or Multi-Gated Acquisition (MUGA) for Left Ventricular Ejection Fraction (LVEF)
• Percentage of Participants with Abnormalities in Clinical Laboratory Tests
• Percentage of Participants with Adverse Events (AEs)
• Percentage of Participants with AEs of Special Interest (AESIs)
• Percentage of Participants with Serious Adverse Events (SAEs)
• Percentage of Participants Using Concomitant Medications
• Units of Platelets and Red Blood Cells (RBC) Infused
• Rate of Infection
• Days Spent Hospitalized
• Change From Baseline in the European Organisation for Research and Treatment of Cancer (EORTC) QLC-C30 Questionnaire
• Change From Baseline in the EORTC EQ-5D-5L Questionnaire
• Percentage of Participants With CR With IDH1 Mutation Clearance (MC)
• Percentage of Participants With Drug Exposure, Dose Modifications and Dose Intensities
• Circulating Plasma Concentration of AG-120 and 2-HG

View this trial on ClinicalTrials.gov