Immunomonitoring of Children With Neuroblastoma for the Development of Antitumor Immunotherapy Strategies
试验速览
- 阶段
- 不适用
- 入组人数
- 35
- 试验地点
- 8
- 主要终点
- Description of immune effectors in the blood, marrow and tumor diagnosis.
研究概览
简要总结
Apart from brain tumors, Neuroblastoma is the most common solid tumor during childhood. About 50% of the cases present at diagnosis with factors of bad prognosis. During the last two decades, despite increased therapeutic intensity during induction and consolidation of high-risk neuroblastomas, the 5 year overall survival of high risk neuroblastoma remains in between 30 to 40% depending on studies.
Besides strategies of high-dose chemotherapy followed by autologous transplantation of hematopoietic stem cells, and differentiating molecules (retinoids), immunotherapy will become one of the leading anti-neuroblastoma targeted therapy. No therapeutic strategies or molecules obtained such gains of survival ever before.
Studying the immune system of children with neuroblastoma at diagnosis and during their treatment will help us to determine when we should test active or passive immunotherapy strategies. Moreover, this study would allow us to specify the cause of tumor immune tolerance in neuroblastoma, on which we have few data in comparison to adult tumors.
This will be a multicentric, pilot, prospective, open, study that will not require unusual diagnostic interventions. This study will be transversal (all neuroblastoma stages included) in order to determine comparative criteria between low and high risk neuroblastoma. It will also be longitudinal (from diagnosis to post-treatment follow-up) in order to specify evolutionary aspects of immunity under radio-chemotherapy and retinoic acid therapy.
Immunological analyses will be done on blood, bone marrow and tumor samples, at diagnosis, and during the treatment of children diagnosed for neuroblastoma (up to 3 time points). These types of samples are routinely done during conventional neuroblastoma treatment.
详细描述
The main objective of the study is the description of immune effectors in the blood, marrow and tumor diagnosis.
During 3 years, this trial will include 30 children from pediatric oncology units of Lyon, Saint-Etienne, Grenoble and Clermont-Ferrand.
The study duration is 5 years. Children follow-up scheduled for at least 2 years in order to determine predictive factors of therapeutic efficiency and survival.
Multi-parametric marker sets (6-8 markers per sample) have already developed and validated for analyzing the absolute amount and proportion of immune subpopulations (B, TCD4+, TCD8+, Treg, NK, DC) and activation status (PD1, ICOS, CD39, CD73, CD62L, CCR7, CD45RO, CD45RA, CD86, Ox40, CD137, CTLA4) on a small volume. At least, these analyses will be performed on each blood and marrow sample. If the amount of blood and mononuclear cells harvested allows it, functional analyses will be undertaken (intracytoplasmic cytokines in response to activation for T, DC, NK; protocols been set up).
Immunostainings will be performed on tumor samples at diagnosis and after resection of the primary tumor, in order to determine the expression and evolution of several immunomodulatory molecules on neuroblastoma cells (HLA class I & II, HLA-G, IDO, IL10,...)., and also determine the immune infiltrate within the tumor microenvironment (lymphocytes Treg, cellules dendritiques, MDSC,...). The techniques used will mostly be those of classical immunology (IHC, IF, FACS), and have already been set-up in our INSERM team for adult tumors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Screening
- 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
- •Age <= 21 years
- •Patient with neuroblastoma any stage, in the first line or relapsed, or suspicion of neuroblastoma
- •Covered by a medical insurance
- •Written, signed informed consent (patient, and parents if minor child)
排除标准
- •Patients who received corticosteroids within 15 days prior to sampling
- •Patients receiving immunosuppressive therapy
- •Chemotherapy before sampling began
- •Neuroblastoma in a genetic syndrome predisposing
- •Deterioration of clinical status
研究组 & 干预措施
Type of neuroblastoma
Neonatal stages I Localized immediately resectable stages Localized immediately unresectable stages High-risk neuroblastoma Relapsed neuroblastoma
干预措施: Immunological analyses (Other)
结局指标
主要结局
Description of immune effectors in the blood, marrow and tumor diagnosis.
时间窗: 1 year
Rate effectors immunitaires in blood, marrow and tumor present at diagnosis
次要结局
未报告次要终点