Randomized Study in Newly Diagnosed AML With FLT3-ITD Comparing Daunorubicin/ Cytarabine or Idarubicin/Cytarabine and Quizartinib to Physician's Choice
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 主要终点
- Modified Event-free survival (mEFS)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Quizartinib plus standard of care (SOC)
Daunorubicin/ Cytarabine or Idarubicin/Cytarabine and Quizartinib
干预措施: Quizartinib (Drug)
Quizartinib plus standard of care (SOC)
Daunorubicin/ Cytarabine or Idarubicin/Cytarabine and Quizartinib
干预措施: Standard of Care Chemotherapy (Drug)
Physician's choice
Physician's choice (usually Daunorubicin/ Cytarabine or Idarubicin/Cytarabine and Midostaurin)
干预措施: Treatment according to Physician's Choice (Drug)
结局指标
主要结局
Modified Event-free survival (mEFS)
时间窗: 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.
次要结局
- Overall survival (OS)(through study completion (up to 4 years), frome randomization until death from any cause)
- Composite remission(End of induction therapy, between 4 and 12 weeks)
- 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))
研究者
Prof. Dr. Richard F Schlenk
Assistant medical director
University Hospital Heidelberg