Phase 1b, Open-label, Dose Escalation Study of Quizartinib in Combination With Induction and Consolidation Chemotherapy in Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 7
- 主要终点
- Summary of Best Responses After a Daily Dose of 20 mg or 40 mg in Combination With Standard Chemotherapy to Japanese Participants With Newly Diagnosed Acute Myeloid Leukemia (AML)
研究概览
简要总结
This is a phase 1b, dose escalation, study of quizartinib to evaluate the safety profile, the pharmacokinetics, and the recommended dose of quizartinib for subsequent clinical studies of the combination of quizartinib and induction and consolidation chemotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •No prior treatment for AML (including quizartinib)
- •ECOG (Eastern Cooperative Oncology Group) Performance Status of 0 to 2
排除标准
- •Diagnosis of acute promyelocytic leukemia
- •Active acute or chronic systemic fungal, bacterial, or viral infection not well controlled by antifungal, antibacterial or antiviral therapy.
研究组 & 干预措施
Quizartinib 20 mg/day
Participants who received 20 mg quizartinib once daily in the morning under fasting conditions.
For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib.
For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib.
干预措施: Quizartinib (Drug)
Quizartinib 20 mg/day
Participants who received 20 mg quizartinib once daily in the morning under fasting conditions.
For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib.
For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib.
干预措施: Cytarabine (Drug)
Quizartinib 20 mg/day
Participants who received 20 mg quizartinib once daily in the morning under fasting conditions.
For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib.
For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib.
干预措施: Idarubicin (Drug)
Quizartinib 20 mg/day
Participants who received 20 mg quizartinib once daily in the morning under fasting conditions.
For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib.
For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib.
干预措施: Daunorubicin (Drug)
Quizartinib 40 mg/day
Participants who received 40 mg quizartinib once daily in the morning under fasting conditions.
For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib.
For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib.
干预措施: Quizartinib (Drug)
Quizartinib 40 mg/day
Participants who received 40 mg quizartinib once daily in the morning under fasting conditions.
For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib.
For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib.
干预措施: Cytarabine (Drug)
Quizartinib 40 mg/day
Participants who received 40 mg quizartinib once daily in the morning under fasting conditions.
For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib.
For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib.
干预措施: Idarubicin (Drug)
Quizartinib 40 mg/day
Participants who received 40 mg quizartinib once daily in the morning under fasting conditions.
For the Induction phase, cytarabine (100 mg/m^2/day IV) and either idarubicin (12 mg/m^2/day IV infusion) or daunorubicin (60 mg/m^2/day IV) were co-administered with quizartinib.
For the Consolidation phase, cytarabine (3.0 g/m^2/12 hours IV) was co-administered with quizartinib.
干预措施: Daunorubicin (Drug)
结局指标
主要结局
Summary of Best Responses After a Daily Dose of 20 mg or 40 mg in Combination With Standard Chemotherapy to Japanese Participants With Newly Diagnosed Acute Myeloid Leukemia (AML)
时间窗: Day 0 to Day 21 of last completed cycle (each cycle 28 days), up to approximately 1 year
Best response was defined as the best measured complete remission (CR), CR with incomplete hematological recovery (CRi), CR with incomplete platelet recovery (CRp), Partial remission (PR), or No response (NR) in the overall response assessments at all time points after the first dose. CR is defined as absence of leukemia cells morphologically; bone marrow blasts \<5 %; neutrophil count ≥ 1000 /mm 3; platelet count ≥ 100 ,000 /mm 3, independence of RBC transfusions for 4 weeks; independence of platelet transfusions for 1 week; absence of extramedullary leukemia.
Summary of Best Response Rates After the First Oral Dose of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia
时间窗: Day 0 to Day 21 of last completed cycle (each cycle 28 days), up to approximately 1 year
Best response was defined as the best measured complete remission (CR), CR with incomplete hematological recovery (CRi), CR with incomplete platelet recovery (CRp), Partial remission (PR), or No response (NR) in the overall response assessments at all time points after the first dose.
Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) of Geometric Means of Quizartinib and Active Metabolite (AC886) After Daily Dose of 20 mg or 40 mg Combined With Chemotherapy to Japanese Participants With Newly Diagnosed Acute Myeloid Leukemia
时间窗: Induction phase Cycle 1, Day 8 to Cycle 1, Day 21 (each cycle 28 days)
The maximum serum plasma concentration (Cmax) is reported at Induction phase Cycle 1, Day 9 and the maximum serum plasma concentration at steady state (Cmax,ss) is reported at Induction phase Cycle 1, Day 21 for quizartinib, active metabolite AC886, and quizartinib and AC886.
Pharmacokinetic Parameter Area Under the Concentration-Time Curve During Dosing Interval of Quizartinib and Metabolite (AC886) After Daily Dose of 20 mg or 40 mg With Chemotherapy to Japanese Participants With Newly Diagnosed Acute Myeloid Leukemia
时间窗: Induction phase Cycle 1, Day 8 to Cycle 1, Day 21 (each cycle 28 days)
The area under the plasma concentration-time curve during dosing interval (AUCtau) of geometric means is reported at Induction phase Cycle 1, Day 9 and the area under the plasma concentration-time curve during dosing interval at steady state (AUCtauss) of geometric means are reported at Induction phase Cycle 1, Day 21 for quizartinib, active metabolite AC886, and quizartinib and AC886.
Pharmacokinetic Parameter Time of Maximum Plasma Concentration (Tmax) of Quizartinib and the Active Metabolite (AC886) After a Daily Dose of 20 mg or 40 mg Combined With Chemotherapy to Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
时间窗: Induction phase Cycle 1, Day 8 to Cycle 1, Day 21 (each cycle 28 days)
The time of maximum plasma concentration (Tmax) of geometric means is reported at Induction phase Cycle 1, Day 9 and the time of maximum plasma concentration at steady state (Tmax,ss) of geometric means is reported at Induction phase Cycle 1, Day 21 for quizartinib, active metabolite AC886, and quizartinib and AC886.
Pharmacokinetic Parameter Metabolite to Parent Ratio (MR) of Active Metabolite (AC886) After a Daily Dose of 20 mg or 40 mg Combined With Chemotherapy to Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
时间窗: Induction phase Cycle 1, Day 8 (each cycle 28 days)
The metabolite to parent ratio of geometric means for Cmax and AUCtau is reported at Induction phase Cycle 1, Day 9 for active metabolite AC886 is reported.
Pharmacokinetic Parameter Trough Plasma Concentration (Ctrough) of Quizartinib and Active Metabolite (AC886) After a Daily Dose of 20 mg or 40 mg Combined With Chemotherapy to Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
时间窗: Induction phase Cycle 1, Day 21 (each cycle 28 days)
The trough plasma concentration (Ctrough) of geometric means is reported at Induction phase Cycle 1, Day 21 for serum quizartinib, active metabolite AC886, and quizartinib and AC886.
Pharmacokinetic Parameter Accumulation Ratio (AR) of Quizartinib and Active Metabolite (AC886) After a Daily Dose of 20 mg or 40 mg Combined With Chemotherapy to Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
时间窗: Induction phase Cycle 1, Day 21 (each cycle 28 days)
The accumulation ratio of geometric means for Cmax and AUCtau is reported at Induction phase Cycle 1, Day 21 for serum quizartinib, active metabolite AC886, and quizartinib and AC886.
Number of Participants Treatment-Emergent Adverse Events Reported During Induction Phase After a Daily Dose of 20 mg or 40 mg in Combination With Standard Chemotherapy to Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
时间窗: Induction phase Cycle 1, Day 1 up to 35 days after last dose in Cycle 2 (each cycle 28 days), up to approximately 1 year
A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that emerges (or worsens) from the first dose of study drug and coadministered drugs to the follow-up visit, 35 days after the last dose of study drug and coadministered drugs, or the start date of new AML post-treatment, whichever was earlier.
Number of Participants Treatment-Emergent Adverse Events Reported During Consolidation Phase After a Daily Dose of 20 mg or 40 mg in Combination With Standard Chemotherapy to Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
时间窗: Consolidation phase Cycle 1, Day 1 up to 35 days after last dose (each cycle 28 days), up to approximately 1 year
A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that emerges (or worsens) from the first dose of study drug and coadministered drugs to the follow-up visit, 35 days after the last dose of study drug and coadministered drugs, or the start date of new AML post-treatment, whichever was earlier.
次要结局
未报告次要终点