Phase I Study of Intraventricular Infusions of Autologous Ex Vivo-Expanded NK Cells in Children With Recurrent/Refractory Malignant Posterior Fossa Tumors of the Central Nervous System. NOAH's (New Opportunity, Advancing Hope) Protocol
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- Maximum tolerated dose (MTD) of natural killer (NK) cells
研究概览
简要总结
This phase I trial studies the side effects and best dose of expanded natural killer cells in treating younger patients with brain tumors that have come back or do not respond to treatment. Infusing a particular type of a patient's own white blood cells called natural killer cells that have been through a procedure to expand (increase) their numbers may work in treating patients with recurrent/refractory brain tumors.
详细描述
PRIMARY OBJECTIVES:
I. To establish the safety, feasibility, efficacy, and maximum tolerated dose (MTD) of administering autologous natural killer (NK) cells that have been propagated ex vivo with artificial antigen-presenting cells (aAPC) and administered directly into the ventricle in recurrent /refractory malignant posterior fossa tumors.
SECONDARY OBJECTIVES:
I. To assess the antitumor activity based on imaging and cytology of autologous NK cell locoregional administration directly into the lateral or fourth ventricle.
II. To determine the persistence of adoptively-transferred expanded NK cells (as performed with excess NK cells, via optional correlative studies).
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
- — 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis: patients with recurrent/refractory medulloblastoma (MB), atypical teratoid (AT)/rhabdoid tumors (RT) or ependymoma involving the brain and/or spine at original diagnosis or relapse; they must have histological verification at diagnosis and/or relapse; patient must have presented with these tumors in the posterior fossa (PF) or relapsed in the PF
- •Patient must have either measurable or evaluable tumor
- •Presence of or determined by neurosurgery to be a candidate for an implanted catheter in the ventricles to receive NK cell infusion
- •Life expectancy of at least 12 weeks in opinion of principal investigator (PI) and/or designee
- •Lansky score of 50 or greater if =<16 years of age or a Karnofsky score of 50 or greater if > 16 years of age (NOTE: patients who are unable to walk because of paralysis, but who are in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score)
- •Neurologic deficits must have been relatively stable for a minimum of 1 week prior to study enrollment
- •Patients must have recovered from the acute toxic effects of all prior anticancer chemotherapy
- •Patient must be 4 weeks off any palliative radiation or craniospinal radiation
- •Absolute neutrophil count (ANC) of >= 1000/uL
- •Platelet count of >= 30,000
- •Hemoglobin of >= 9.0 g/dl
- •Patients with a seizure disorder may be enrolled if well-controlled and on non-enzyme inducing anticonvulsants
- •Patient or patient's legal representative, parent(s), or guardian able to provide written informed consent
排除标准
- •Enrolled in another treatment protocol
- •Evidence of untreated infection
- •Extra-cranial metastasis
- •Chronic corticosteroid dependence (except replacement therapy)
- •Extensive disease, disease location, and/or co-morbid condition that the PI or designee considers unsafe for surgical intervention of NK cell infusion
- •Pregnant or lactating women
结局指标
主要结局
Maximum tolerated dose (MTD) of natural killer (NK) cells
时间窗: 4 weeks
Defined as the highest dose studied in which 6 patients have been treated at most 1 patient with dose limiting toxicities are observed. Toxicities will be summarized by tabulation in terms of type, grade and attribution for each dose level of each group of patients studied at the end of the trial.
次要结局
- Activation status of NK cells(Up to 30 days after the last infusion in course 3)
- Response of medulloblastoma to NK cells(Up to 30 days after the last infusion in course 3)
- Persistence of NK cells(Up to 30 days after the last infusion in course 3)
- Function of NK cells(Up to 30 days after the last infusion in course 3)
- Feasibility of NK cell manufacturing(Up to 12 weeks)
- Feasibility of delivering NK cells(Up to 12 weeks)