A Phase I/II, Open-label, Dose-escalating Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Twice Daily Oral Midostaurin and to Evaluate the Preliminary Clinical and Pharmacodynamic Response in Pediatric Patients With Relapsed or Refractory Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 22
- 试验地点
- 2
- 主要终点
- Maximum Tolerated Dose (MTD) of Midostaurin- Posterior Probability of DLT
研究概览
简要总结
This is a phase I/II pediatric dose-ranging study that will evaluate the safety, tolerability, clinical response, pharmacokinetics and pharmacodynamics of midostaurin in patients <18 years of age who have relapsed or refractory acute leukemias that may benefit from administration of midostaurin, including MLL-rearranged ALL and FLT3 positive AML.
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
- 3 Months 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Mixed-lineage leukemia (MLL) gene rearranged Acute Lymphoblastic Leukemia (ALL), that does not respond to treatment or has relapsed from prior treatment; or FLT3 mutated Acute Myeloid Leukemia (AML) that does not respond to a second treatment or has relapsed from 2 prior treatments
- •Normal organ function, and chest x-ray
- •Expected survival greater than 8 weeks
- •Can care for most of personal needs and perform at least minimum activity
排除标准
- •Patients with symptomatic leukemic central nervous system involvement or isolated extramedullary leukemia
- •Patients must not have received other treatments for leukemia within a predefined time period, 72 hours for medications, 2 months for transplants
- •Patients with heart function that is not normal
- •Patients with HIV or hepatitis
- •Patients with another severe disease or medical condition besides leukemia Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
30 mg/m^2 bid
Participants received bodyweight and body surface area (BSA) stratified dose of midostaurin 30 mg/m^2 twice daily (bid) through oral route. The total daily dose in 30 mg/m^2 bid cohort was 60 mg/m^2.
干预措施: midostaurin (Drug)
60 mg/m^2 bid
Participants received bodyweight and BSA stratified dose of midostaurin 60 mg/m^2 bid through oral route. The total daily dose in 60 mg/m^2 bid cohort was 120 mg/m^2.
干预措施: midostaurin (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Midostaurin- Posterior Probability of DLT
时间窗: Baseline, End of dose escalation phase (6 months)
MTD was defined as highest dose level for which no more than 1 participant in a dose cohort experienced dose limiting toxicity (DLT), based on a Bayesian logistic regression model (BLRM) employing the escalation with overdose control (EWOC) principle. A DLT was defined as a grade 3 or 4 non-hematological adverse event (AE) or abnormal laboratory value related to study drug. Mean and the 95% posterior probability estimates of having a DLT by age strata and dose is presented. Estimation of MTD and/or recommended dose for expansion (RDE) at the dose-escalation phase of the study was based upon the estimation of the probability of DLT for participants in the dose-determining set (DDS).
次要结局
- Percentage of Participants With Best Overall Response by Indication(Baseline, Day 15 (Day 1 of Cycle 2), Day 22 (Day 8 of Cycle 2), Day 29(Day 1 of Cycle 9), End of treatment (up to 24 months after last dose or until death whichever occurred first))
- Time to Response With Midostaurin(Baseline, End of treatment (up to 24 months after last dose or until death whichever occurred first))
- Overall Survival With Midostaurin(Baseline, End of treatment (up to 24 months after last dose or until death whichever occurred first))
- Plasma Concentrations of Midostaurin and Its Metabolites CGP52421 and CGP62221(Day 1, Day 5, Day 7, Day 15 (Day 1 of Cycle 2), Day 29 (Day 1 of Cycle 3))
- Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment Related AEs or SAEs and Death During the Study(Baseline (start of study treatment) up to End of treatment (up to 24 months after last dose or until death whichever occurred first))