NCT03793478

Safety and Efficacy of Quizartinib in Children and Young Adults With Acute Myeloid Leukemia (AML), a Cancer of the Blood

A Phase 1/2, Multicenter, Dose-Escalating Study To Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy Of Quizartinib Administered in Combination With Re-Induction Chemotherapy, and as a Single-Agent Continuation Therapy, in Pediatric Relapsed/Refractory AML Subjects Aged 1 Month to <18 Years (and Young Adults Aged up to 21 Years) With FLT3-ITD Mutations

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 65 (estimated)
• Sponsor: Daiichi Sankyo · Industry
• Sex: All
• Age: 1 Month – 21 Years
• Healthy volunteers: Not accepted

Summary

Quizartinib is an experimental drug. It is not approved for regular use. It can only be used in medical research. Children or young adults with a certain kind of blood cancer (FLT3-ITD AML) might be able to join this study if it has come back after remission or is not responding to treatment.

Detailed description

The medical condition being investigated is relapsed or refractory AML in participants aged ≥1 month to ≤21 years with Feline McDonough Sarcoma (FMS)-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) mutations (FLT3-ITD AML), following failure of front-line intensive chemotherapy. The trial will be conducted in multiple phases. An independent data monitoring committee (DMC) will protect the rights, safety, and well-being of participants by monitoring the progress and results. The DMC will comprise qualified physicians and scientists who are not Investigators in the study and not otherwise directly associated with the Sponsor and will be convened at the end of Phase 1. A. Dose Escalation/De-escalation Phase: Number of participants is determined by age group. Participants will be enrolled by dose-level to determine the recommended Phase 2 dose (RP2D) of quizartinib for pediatric participants that provides similar exposure to adult patients treated at the target adult dose of 60 mg orally once daily. B. Dose-Expansion Phase: Participants will receive the RP2D of quizartinib for their respective age group. During both dose escalation and dose expansion phases, participants will receive: Re-Induction Therapy * Intrathecal (IT) triple chemotherapy prophylaxis prior to and between cycles * In re-induction Cycles 1 and 2, fludarabine/cytarabine (FLA) followed by quizartinib as a single agent Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) Period: After re-induction therapy, participants will be evaluated for eligibility to undergo allogeneic hematopoietic stem cell transplant (HSCT). Eligible participants may receive a single 28-day cycle of consolidation therapy (standard of care chemotherapy with or without quizartinib) if an allogeneic HSCT is not available immediately. The options for consolidation therapy are as follows: * High intensity chemotherapy with quizartinib, or * Low intensity chemotherapy alone, or * Low intensity therapy with quizartinib as a single agent Continuation Therapy: Participants in remission after HSCT, or who are not eligible for HSCT but achieve at least a partial remission (PR) after re-induction, will receive up to 12 continuous 28-day cycles of quizartinib continuation therapy at the same dose received during re-induction in the dose expansion phase. Long-term Follow-up: The long-term follow-up phase begins upon completion of 12 cycles of quizartinib Continuation Therapy or permanent discontinuation of quizartinib at any time. After completion of the 30-day safety follow-up visit, subsequent visits will occur at the following frequencies to assess survival and anti-leukemic treatments: * every 3 months for the first 2 years, and then * once a year thereafter until the last participant enrolled has been followed for three years from the date of enrollment

Conditions

• Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	Quizartinib	Administered orally once daily starting on Day 6 and continuing through Day 28; Optional low intensity consolidation with chemotherapy: Administered orally once daily starting on Day 1 and continuing through Day 28
DRUG	Fludarabine	30 mg/m\^2/day IV infusion given over 30 minutes on Days 1 through 5 (administered based on body weight)
DRUG	Cytarabine	2000 mg/m\^2/day IV infusion given over 3 hours on Days 1 through 5 (begin 4 hours after the start of fludarabine) (administered in accordance with standard of care); Optional high intensity consolidation with chemotherapy and quizartinib: 500 mg/m\^2/day as a continuous 96-hour IV infusion on Days 1 through 4; Optional low intensity consolidation with chemotherapy: 75 mg/m\^2/day as once daily subcutaneous or IV on Days 1 through 4 and Days 15 through 18
DRUG	Intrathecal (IT) triple chemotherapy prophylaxis	IT cytarabine, methotrexate, and either prednisolone or hydrocortisone; doses are based on the participant's age and standard practice at each site
DRUG	Etoposide	Optional high intensity consolidation with chemotherapy and quizartinib: 100 mg/m\^2/dose once daily as an IV infusion over 3 hours on Days 1 through 5

Timeline

• Start date: 2018-08-15
• Primary completion: 2027-05-01
• Completion: 2027-05-01
• First posted: 2019-01-04
• Last updated: 2026-04-01

Locations

27 sites across 10 countries: United States, Belgium, Canada, Denmark, France, Israel, Italy, Netherlands, Spain, Sweden

Regulatory

• FDA-regulated drug study