Phase 1/2 Dose Finding and Safety Study of Ibrutinib in Pediatric Subjects With Chronic Graft Versus Host Disease (cGVHD)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 59
- 试验地点
- 48
- 主要终点
- Number of patients with adverse events as a measure of safety and tolerability
研究概览
简要总结
Dose Finding and Safety Study of Ibrutinib in Pediatric Subjects with Chronic Graft Versus Host Disease (cGVHD)
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 Year 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Part A: Subjects with moderate or severe cGVHD after failure of 1 or more lines of systemic therapy
- •Part B: Subjects with moderate or severe cGVHD after failure of 1 or more lines of systemic therapy, or subjects with new onset moderate or severe cGVHD and in need of systemic immunosuppression
- •History of allogeneic stem cell transplantation
- •Part A: ≥1 to <12 years of age at the time of enrollment
- •Part B: ≥1 to <22 years of age at the time of enrollment
- •Karnofsky or Lansky (subjects <16 years of age) performance status ≥60
- •Key Eligibility:
排除标准
- •Presence of single organ genito-urinary involvement as the only manifestation of cGVHD
- •Received an investigational agent within 28 days before enrollment.
- •Received donor lymphocyte infusion (DLI) within 56 days before enrollment
- •Progressive underlying malignant disease or active post-transplant lymphoproliferative disease
- •Any uncontrolled infection or active infection requiring ongoing systemic treatment
- •Known bleeding disorders
- •Active hepatitis C virus (HCV) or hepatitis B virus (HBV)
研究组 & 干预措施
Phase 1/2
Part A: Subjects ≥1 to <12 years of age with moderate or severe cGVHD after failure of 1 or more lines of systemic therapy, will receive oral ibrutinib once daily to determine Recommended Pediatric Equivalent Dose (RPED).
Part A Continuation: Subjects participating in Part A may continue receiving daily ibrutinib until the RPED is determined, at which time their dose may be adjusted to the RPED.
Part B: Subjects ≥1 to <12 years of age( upper age limit is < 22 years) with moderate or severe cGVHD after failure of 1 or more lines of systemic therapy or with newly diagnosed moderate or severe cGVHD will be dosed at the RPED. Subjects ≥12 will be given 420mg orally ibrutinib once daily.
干预措施: Ibrutinib (Drug)
结局指标
主要结局
Number of patients with adverse events as a measure of safety and tolerability
时间窗: Approximately 7 years
Part A- PK (measured by AUC) will be reported descriptively
时间窗: Approximately 24 months
Part B- PK (measured by AUC) will be reported descriptively
时间窗: Approximately 7 years
次要结局
- Part A continuation cohort and Part B-Response rate at 24 weeks(Approximately 6 months after last subject in enrolled)
- Part A continuation cohort and Part B- Duration of response (DOR)(Up to 48 weeks)
- Growth Parameter weight in kilograms will be reported descriptively.(Up to 5 years post enrollment)
- Available immune reconstitution laboratory parameters will be reported descriptively(Up to 5 years post enrollment)
- Late effects (Adverse events suspected to be related to treatment) will be quantified and reported descriptively(Up to 5 years post enrollment)
- Growth Parameter height in meters will be reported descriptively(Up to 5 years post enrollment)
- Part A- Number of patients with adverse events as a measure of safety and tolerability(Approximately 24 months)
- Part A- Pharmacodynamic effects as measured by in vitro BTK occupancy will be reported descriptively(Approximately 24 months)
- Part A continuation cohort and Part B-Overall survival (OS)(Approximately 5 years after last subject enrolled)
- Part A continuation cohort and Part B-Late Effects Surveillance(Up to 5 years post enrollment)