Quizartinib is an experimental drug. It is not approved for regular use. It can only be used in medical research. Adults might be able to join this study after bone marrow tests show they have a certain kind of blood cancer (FLT3-ITD AML). Participants will have an equal chance of receiving quizartinib or placebo along with their chemotherapy.
This is a phase 3, randomized, double-blind, placebo-control global study. The purpose of this study is to compare the effect of quizartinib versus placebo (administered with standard induction and consolidation chemotherapy, then administered as continuation therapy for up to 36 cycles) on overall survival in subjects with FLT3-internal tandem duplication (ITD) positive AML.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
539
Overall Survival in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia
Overall survival is defined as the time from randomization until death from any cause.
Time frame: Date of randomization to the date of death due to any cause, up to approximately 3 years after enrollment
Event-free Survival in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia
Event-free survival (EFS) is the time from randomization to the earliest date of either refractory disease (or treatment failure \[TF\]), relapse, or death from any cause. Refractory disease is defined as complete remission never achieved during Induction (CR: \>1000 neutrophils, \>100,000 platelets, \<5% blasts, and other \[defined as absence of extramedullary disease \[EMD\], blasts with rods, and leukemic blasts\]). For refractory disease, EFS event date is Day 1 (randomization). Relapse after CR is defined as ≥5% blasts, leukemic blasts, extramedullary leukemia, and presence of rods. This analysis is based on a response assessment with TF defined as not achieving response of CR, using a 42- day window from the start of the last cycle in Induction for CR evaluation.
Time frame: Date of randomization to the date of refractory disease, relapse, or death, up to approximately 3 years after enrollment
Complete Remission (CR) Rate at the End of Induction in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia
Complete remission (CR) rate is defined as the percentage of participants achieving CR, defined as \<5% blasts, \>1000 neutrophils, \>100,000 platelets, and other \[defined as absence of extramedullary disease \[EMD\], blasts with rods, and leukemic blasts\], after induction
Time frame: Approximately Cycle 1 Day 21 (Induction) to end of Induction, up to approximately 120 days (each Induction cycle is up to 60 days)
Composite CR Rate at the End of Induction in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia
Composite complete remission (CRc) rate is defined as the percentage of participants whose best response is complete remission (CR), defined as \<5% blasts, \>1000 neutrophils, \>100,000 platelets, and other \[defined as absence of extramedullary disease \[EMD\], blasts with rods, and leukemic blasts\], or CR with incomplete neutrophil or platelet recovery (CRi) at the end of first Induction cycle.
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University of Florida (UF) Health Shands Hospital
Gainesville, Florida, United States
The University of Chicago Medical Center
Chicago, Illinois, United States
Franciscan St. Francis Health Indianapolis
Indianapolis, Indiana, United States
University of Kentucky Chandler Medical Center
Lexington, Kentucky, United States
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, United States
NY Medical College - Hudson Valley Hematology Oncology Associates
Valhalla, New York, United States
Duke Clinical Research Institute
Durham, North Carolina, United States
University Hospitals Seidman Cancer Center
Cleveland, Ohio, United States
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States
...and 234 more locations
Time frame: Approximately Cycle 1 Day 21 (Induction) to end of Induction, up to approximately 120 days (each Induction cycle is up to 60 days)
Number of Participants With Treatment-emergent Adverse Events Occurring in ≥10% Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia
A treatment-emergent adverse event (TEAE) is defined as an adverse event that occur, having been absent before first dose of quizartinib or placebo, or have worsened in severity after initiating quizartinib or placebo. Adverse events collected more than 30 days after the last dose of quizartinib/placebo will not be considered TEAEs unless they are considered drug-related.
Time frame: Date of first dose up to 30 days after last dose, up to 36 cycles following continuation (approximately 6 years 11 months, each cycle is 28 days)
Number of Participants Achieving CR With FLT3-ITD Minimal Residual Disease Negativity at the End of Induction in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia
Complete remission (CR) is defined as participants achieving CR defined as \<5% blasts, \>1000 neutrophils, \>100,000 platelets, and other \[defined as absence of extramedullary disease \[EMD\], blasts with rods, and leukemic blasts\]. Minimal or measurable residual disease is the presence of a small number of leukemic cells in the bone marrow of patients with AML below the level of detection using conventional morphologic assessment.
Time frame: Approximately Cycle 1 Day 21 (Induction phase) to end of Induction phase, up to approximately 120 days (each Induction cycle is up to 60 days)
Number of Participants Achieving Composite CR With FLT3-ITD Minimal Residual Disease Negativity at the End of Induction in Participants With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia
Composite complete remission (CRc) is defined as \<5% blasts, \>1000 neutrophils, \>100,000 platelets, and other \[defined as absence of extramedullary disease \[EMD\], blasts with rods, and leukemic blasts\], or CR with incomplete neutrophil or platelet recovery (CRi). Minimal or measurable residual disease is the presence of a small number of leukemic cells in the bone marrow of patients with AML below the level of detection using conventional morphologic assessment.
Time frame: Approximately Cycle 1 Day 21 (Induction phase) to end of Induction phase, up to approximately 120 days (each Induction cycle is up to 60 days)
Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve at Steady State
AUCss was assessed by population Pharmacokinetic (PK) analysis during Cycle 1 of each phase.
Time frame: Induction Cycle 1: Day 8, predose, 2-4 hours (hr) postdose on Days 8, 15, 21; Consolidation Cycle 1: Day 6, predose, 2-4 hr postdose on Days 6, 13, 19; Continuation Cycle 1: 2-4 hr postdose, Days 1, 8, 15; Cycle 2 Days 1 and 15 (each cycle, 28 days)
Pharmacokinetic Parameter Steady State, Maximum Plasma Concentration (Css,Max)
Css,max was assessed by population PK analysis during Cycle 1 of each phase.
Time frame: Induction Cycle 1: Day 8, predose, 2-4 hours (hr) postdose on Days 8, 15, 21; Consolidation Cycle 1: Day 6, predose, 2-4 hr postdose on Days 6, 13, 19; Continuation Cycle 1: 2-4 hr postdose, Days 1, 8, 15; Cycle 2 Days 1 and 15 (each cycle, 28 days)
Pharmacokinetic Parameter Time to Maximum Plasma Concentration Steady State (Tmax,ss)
Tmax,ss was assessed by population PK analysis during Cycle 1 of each phase.
Time frame: Induction Cycle 1: Day 8, predose, 2-4 hours (hr) postdose on Days 8, 15, 21; Consolidation Cycle 1: Day 6, predose, 2-4 hr postdose on Days 6, 13, 19; Continuation Cycle 1: 2-4 hr postdose, Days 1, 8, 15; Cycle 2 Days 1 and 15 (each cycle, 28 days)