Phase Ib /II Clinical Trial of Nivolumab Monotherapy and Nivolumab in Combination With Ipilimumab in Pediatric Subjects With High Grade Primary CNS Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 166
- 试验地点
- 105
- 主要终点
- Number of Safety Lead-In Participants With Dose Limiting Toxicities (DLTs)
研究概览
简要总结
The purpose of this study is to determine the safety and effectiveness of nivolumab alone and in combination with ipilimumab in pediatric patients with high grade primary central nervous system (CNS) malignancies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Months 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must have received standard of care therapy, and there must be no potentially-curative treatment available, in one of the following cohorts:
- •A newly diagnosed Diffuse Intrinsic Pontine Glioma (DIPG) that has been treated with radiation therapy (RT) but no chemotherapy
- •A histologically confirmed recurrent or progressive non-brainstem High Grade Glioma (HGG) previously treated with surgical resection and RT
- •A histologically confirmed medulloblastoma that has relapsed or is resistant to at least one line of prior therapy including surgery, RT, and chemotherapy
- •A histologically confirmed ependymoma that has relapsed or is resistant to at least one line of prior therapy including surgical resection and RT
- •A histologically-confirmed high grade CNS malignancy "other than above" which is recurrent or progressive after at least one line of prior therapy
- •Lansky play score (LPS) for ≤ 16 years of age or Karnofsky performance scale (KPS) for > 16 years of age assessed within two weeks of enrollment must be >= 60
- •A tumor sample must be available for submission to central laboratory (not required for DIPG)
排除标准
- •An active, known, or suspected autoimmune disease
- •A concurrent condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of start of study treatment
- •Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
- •Other protocol defined inclusion/exclusion criteria apply
结局指标
主要结局
Number of Safety Lead-In Participants With Dose Limiting Toxicities (DLTs)
时间窗: up to 6 weeks post-dosing
A dose-limiting toxicity (DLT) is defined as a drug-related AE occurring in the first 6 weeks of study treatment. A participant was considered evaluable for a DLT if study treatment was delayed \> 2 weeks or was discontinued due to a related Adverse Event (AE), or if planned study treatment (3 doses of nivolumab in Module A, 2 doses of nivolumab plus ipilimumab in Module B) was administered and safety evaluation after 6 weeks on study is available to the study steering committee (SSC).
Number of Safety Lead-In Participants With Serious Adverse Events (SAEs)
时间窗: up to 6 weeks post-dosing
The number of Safety Lead-In Participants who experienced a Serious Adverse Event (SAE) during the course of the study.
Overall Survival (OS), Cohort 1 Only
时间窗: up to approximately 42 months
Overall survival (OS) is defined as the time between the date of diagnosis and the date of death in Cohort 1.
Progression-Free Survival (PFS), Cohorts 2-4
时间窗: up to approximately 42 months
Progression-free survival (PFS) is defined as the time from first dose to the date of the first documented tumor progression or death due to any cause.
Number of Safety Lead-In Participants With Adverse Events (AEs) Leading to Discontinuation
时间窗: From first dose to 30 days post-last dose (up to approximately 6 weeks)
The number of Safety Lead-In Participants who experienced an Adverse Event (AE) during the course of the study that lead to discontinuation of study therapy.
Progression-Free Survival (PFS), Cohort 5 Only
时间窗: up to approximately 42 months
Progression-free survival (PFS) is defined as the time from first dose to the date of the first documented tumor progression or death due to any cause.
次要结局
- Overall Survival (OS), Cohorts 2-5(From first dose to the date of death (up to approximately 55 months))
- Progression-Free Survival (PFS), Cohort 1 Only(From first dose to the date of the first documented tumor progression or death due to any cause (up to approximately 55 months))
- Number of Treated Participant With Laboratory Abnormalities - Liver(From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months))
- Overall Survival at 12 Months (OS12), Cohorts 1-4(From first dose to up to 12 months after first dose)
- Progression-Free Survival at 6 Months (PFS6), Cohorts 2-5(From first dose to up to 6 months after first dose)
- Number of Treated Participants With Adverse Events (AEs)(From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months))
- Number of Treated Participants With Serious Adverse Events (SAEs)(From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months))
- Number of Treated Participants With Drug-Related Adverse Events(From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months))
- Number of Treated Participants With Adverse Events Leading to Discontinuation(From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months))
- Number of Treated Participant With Laboratory Abnormalities - Thyroid(From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months))
- Number of Treated Participant Deaths(From first dose to the date of death (up to approximately 55 months))