Daunorubicin or Idarubicin With Cytarabine Plus Quizartinib vs Physician's Choice in Newly Diagnosed FLT3-ITD+ AML
- Conditions
- Acute Myeloid Leukemia
- Interventions
- Registration Number
- NCT04676243
- Lead Sponsor
- University Hospital Heidelberg
- Brief 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.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Quizartinib plus standard of care (SOC) Quizartinib Daunorubicin/ Cytarabine or Idarubicin/Cytarabine and Quizartinib Quizartinib plus standard of care (SOC) Standard of Care Chemotherapy Daunorubicin/ Cytarabine or Idarubicin/Cytarabine and Quizartinib Physician's choice Treatment according to Physician's Choice Physician's choice (usually Daunorubicin/ Cytarabine or Idarubicin/Cytarabine and Midostaurin)
- Primary Outcome Measures
Name Time Method Modified Event-free survival (mEFS) through study completion (up to 4 years), from randomization until occurence of event a) b) or c) on individial patients' basis mEFS is defined as the time from randomization until one of the following events, whichever occurs first: a) failure to obtain complete remission (CR) or complete remission with incomplete hematological recovery (CRi) or CR with partial recovery of peripheral blood counts (CRh) after induction therapy including one or two induction treatment cycles limited to an observational period of maximally 100 days, b) relapse from CR/CRi/CRh or c) death from any cause.
- Secondary Outcome Measures
Name Time Method Overall survival (OS) through study completion (up to 4 years), frome randomization until death from any cause OS is defined as the time from randomization to time of death from any cause. Patients without event are censored on the last date of follow-up.
Composite remission End of induction therapy, between 4 and 12 weeks Composite remission is defined as the proportion of patients experiencing a CR/CRi/CRh after induction therapy.
Measurable residual disease (MRD) End of induction thearpy (28-84 days from randomization), End of consolidation therapy (140-222 days from randomization), End of maintenance therapy (140-1,120 days from randomization) MRD after induction (MRDind), consolidation (MRDcons), and maintenance (MRDmaintenance) therapy, MRD is assessed by flow cytometry according to European Leukemia Net recommendations (Döhner et al, Blood 2017;129(4):424-447.)