A Phase II, Single Arm, Open Label, Study on the Safety, Efficacy, Pharmacokinetics & Pharmacodynamics of Quizartinib + Chemotherapy and as Single-agent After High Dose Therapy in Newly Diagnosed Pediatric FLT3-ITD+ and NPM1wt AML Patients
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Primary objective (efficacy)
研究概览
简要总结
The CHIP-AML22 Master protocol has the overall aim of increasing the cure rate in newly diagnosed pediatric de novo AML patients, while avoiding unnecessary toxicity. The linked Quizartinib trial (CHIP-AML22/Quizartinib) is a phase II, single arm, open label, study on the safety, efficacy, pharmacokinetics and pharmacodynamics of quizartinib in combination with chemotherapy and as single-agent after high dose therapy in newly diagnosed pediatric AML patients with a FLT3-ITD mutation and NPM1 wild-type.
详细描述
The CHIP-AML22/Quizartinib study is a single-arm, multinational, multicenter, open-label phase II study, with a safety run-in, aiming to assess the safety, efficacy, pharmacokinetics and pharmacodynamics of quizartinib, a FLT3-inhibitor, as IMP added to standard of care chemotherapy in newly diagnosed FLT3-ITD positive and NPM1 wild-type AML pediatric patients.
This study is a linked trial to the CHIP-AML22/Master protocol. Patients will start in the CHIP-AML22/Master study and if they are FLT3-ITD positive and NPM1 wild-type, can be enrolled in the CHIP-AML22/Quizartinib study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Month 至 18 Years（Child, 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
Quizartinib will be administered for 14 days following the completion of standard of care chemotherapy for up to 3-5 cycles of induction and consolidation. After high dose chemotherapy or allo-Stem Cell Transplantation (allo-SCT), patients will receive continuation treatment with quizartinib for six 28-day courses
干预措施: Quizartinib (Drug)
Quizartinib
Quizartinib will be administered for 14 days following the completion of standard of care chemotherapy for up to 3-5 cycles of induction and consolidation. After high dose chemotherapy or allo-Stem Cell Transplantation (allo-SCT), patients will receive continuation treatment with quizartinib for six 28-day courses
干预措施: Etoposide (Drug)
Quizartinib
Quizartinib will be administered for 14 days following the completion of standard of care chemotherapy for up to 3-5 cycles of induction and consolidation. After high dose chemotherapy or allo-Stem Cell Transplantation (allo-SCT), patients will receive continuation treatment with quizartinib for six 28-day courses
干预措施: Dexrazoxane (Drug)
Quizartinib
Quizartinib will be administered for 14 days following the completion of standard of care chemotherapy for up to 3-5 cycles of induction and consolidation. After high dose chemotherapy or allo-Stem Cell Transplantation (allo-SCT), patients will receive continuation treatment with quizartinib for six 28-day courses
干预措施: Mitoxantrone (Drug)
Quizartinib
Quizartinib will be administered for 14 days following the completion of standard of care chemotherapy for up to 3-5 cycles of induction and consolidation. After high dose chemotherapy or allo-Stem Cell Transplantation (allo-SCT), patients will receive continuation treatment with quizartinib for six 28-day courses
干预措施: Cytarabine (Drug)
Quizartinib
Quizartinib will be administered for 14 days following the completion of standard of care chemotherapy for up to 3-5 cycles of induction and consolidation. After high dose chemotherapy or allo-Stem Cell Transplantation (allo-SCT), patients will receive continuation treatment with quizartinib for six 28-day courses
干预措施: Methotrexate (Drug)
Quizartinib
Quizartinib will be administered for 14 days following the completion of standard of care chemotherapy for up to 3-5 cycles of induction and consolidation. After high dose chemotherapy or allo-Stem Cell Transplantation (allo-SCT), patients will receive continuation treatment with quizartinib for six 28-day courses
干预措施: Daunorubicin (Drug)
Quizartinib
Quizartinib will be administered for 14 days following the completion of standard of care chemotherapy for up to 3-5 cycles of induction and consolidation. After high dose chemotherapy or allo-Stem Cell Transplantation (allo-SCT), patients will receive continuation treatment with quizartinib for six 28-day courses
干预措施: Fludarabine (Drug)
Quizartinib
Quizartinib will be administered for 14 days following the completion of standard of care chemotherapy for up to 3-5 cycles of induction and consolidation. After high dose chemotherapy or allo-Stem Cell Transplantation (allo-SCT), patients will receive continuation treatment with quizartinib for six 28-day courses
干预措施: allo-SCT (Other)
结局指标
主要结局
Primary objective (efficacy)
时间窗: 2 induction courses (maximum of 56+/-2 days per course)
The percentage of patients with (Minimal Residual Disease) MRD levels \<0.1% (MRD negativity) after up to 2 courses of induction chemotherapy plus quizartinib, as measured in the bone marrow using multiparameter flow cytometry (MFCM) before start of consolidation therapy, in the evaluable population for response. o Patients to be evaluated at baseline, end of cycle 1, and end of cycle 2
Primary objective (safety)
时间窗: 2 induction courses (maximum of 56+/-2 days per course)
Incidence of Dose-Limiting Toxicities (DLTs) assessed during Induction course 1 and 2 (until day 56 of each course) for the DLTs evaluable patients.
次要结局
- Secondary objectives (efficacy_6)(3 years)
- Pharmacokinetics (PK_2)(1.5 years)
- Secondary objectives (efficacy_1)(2 induction courses (maximum of 56+/-2 days per course))
- Pharmacokinetics (PK_1)(1.5 years)
- Secondary objectives (efficacy_2)(Multiple time points, last time point after continuation treatment (1.5 years))
- Secondary objectives (efficacy_8)(1 year)
- Secondary objectives (safety) - Adverse Events, Laboratory Abnormalities and cumulative incidence of non-relapse mortality(1.5 years)
- Pharmacokinetics (PK_3)(1.5 years)
- Pharmacokinetics (PK_4)(1.5 years)
- Palatability of quizartinib formulations(1.5 years)
- Secondary objectives (efficacy_3)(3 years)
- Secondary objectives (efficacy_4)(3 years)
- Secondary objectives (efficacy_5)(3 years)
- Secondary objectives (efficacy_7)(3 years)
- Secondary objectives (efficacy_9)(1.5 years)