NCT04676243

Daunorubicin or Idarubicin With Cytarabine Plus Quizartinib vs Physician's Choice in Newly Diagnosed FLT3-ITD+ AML

Randomized Study in Newly Diagnosed AML With FLT3-ITD Comparing Daunorubicin/ Cytarabine or Idarubicin/Cytarabine and Quizartinib to Physician's Choice

• Status: Withdrawn
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: University Hospital Heidelberg · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The orally administered second-generation bis-aryl urea tyrosine kinase inhibitor quizartinib is very specific for FLT3, has a high capacity for sustained FLT3-inhibition and an acceptable toxicity profile. Furthermore, single agent quizartinib doubled the response rate as compared to standard of care in a randomized study in r/r-AML. Combination therapy of quizartinib with intensive standard induction chemotherapy has been shown to be safe and moreover, single agent quizartinib maintenance therapy is feasible even after allogeneic HCT. The efficacy of quizartinib in combination with intensive induction and post-remission therapy including allogeneic HCT and single agent quizartinib as maintenance therapy is evaluated by this protocol. This approach is compared in a randomized manner to the current standard of care.

Detailed description

This is a multicenter, upfront randomized phase III trial of patients with FLT3-ITD positive AML comparing quizartinib in combination with SOC chemotherapy versus treatment according to physician's choice (PhC). Efficacy is assessed by comparing EFS between the quizartinib and the PhC arm of the study. Primary objective To improve modified event-free survival (mEFS) with Quizartinib added to induction and consolidation therapy followed by single agent maintenance therapy compared to physician's choice (PhC) Secondary objectives To improve overall survival (OS) with Quizartinib added to conventional therapy compared to physician's choice; To improve remission (including CR/CRi/CRh) rate with Quizartinib added to conventional therapy compared to physician's choice To reduce measurable residual disease (MRD) with Quizartinib added to conventional therapy compared to physician's choice after induction (MRDind), consolidation (MRDcons), before allogeneic hematopoietic cell transplantation (MRDpre-HCT ) and maintenance (MRDmaintenance) therapy Assessment of patient reported outcomes (PRO) after induction, consolidation and maintenance therapy and after two years Evaluation of safety based on duration of neutropenia and leukopenia, incidence of infection, duration of initial hospitalization and number of transfusions (e.g. packed red blood cells and platelets) Cost-effectiveness analysis of the two different treatment schedules from health care payer´s perspective. Budget impact analysis of introducing effective treatment schedule(s) in everyday clinical practice.

Conditions

• Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	Quizartinib	20 mg coated tablets, orally administered
DRUG	Treatment according to Physician's Choice	Usually daunorubicin/ cytarabine or idarubicin/Cytarabine plus FLT3 inhibitor (usually midostaurin)
DRUG	Standard of Care Chemotherapy	Daunorubicin/ Cytarabine or Idarubicin/Cytarabine

Timeline

• Start date: 2022-05-01
• Primary completion: 2025-05-01
• Completion: 2025-12-01
• First posted: 2020-12-19
• Last updated: 2022-05-25