ANBL0032, PHASE III RANDOMIZED STUDY OF CHIMERIC ANTI-GD2 IN HIGH RISK NEUROBLAE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 神经母细胞瘤是儿童最常见的第三种恶性肿瘤。1-2超过一半的患者患有高危肿瘤，尽管接受了积极的治疗(3年无事件生存率低于15%)，但预后很差。3-4经过强化化疗后，自体骨髓移植获得了一定程度的改善。5-7然而，超过一半的患者仍然会复发并死于肿瘤。对于那些在1岁后被诊断为IV期神经母细胞瘤的患者尤其如此。 治愈这些患者的主要障碍来自难治性的显微镜疾病。一种有前景的方法是针对肿瘤相关抗原GD2的免疫治疗，已证明GD2在神经母细胞瘤、一些黑色素瘤、脑肿瘤、肺小细胞癌12和一些肉瘤中统一表达。 在正常组织中，GD2在神经母细胞瘤中的表达受限，在正常组织中的分布受限，这使得抗GD2的单抗适合于肿瘤的靶向免疫治疗。抗肿瘤单抗的临床试验表明，针对GD2的单抗可能在癌症的被动免疫治疗中有用。主要目的是确定在ASCT前有反应的高危神经母细胞瘤患者中，与单独使用RA相比，CH14.18+细胞因子+13-顺式维甲酸(RA)是否能改善清髓治疗和干细胞挽救后的无事件生存率和总生存率。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Neuroblastoma is the third most common malignancy of childhood.1-2 More than one half of patients have high-risk tumors and have dismal outcome despite aggressive therapy (3 year event-free survival less than 15%).3-4 A somewhat improved outcome has been obtained with autologous bone marrow transplantation after intensive chemotherapy.5-7 However, more than one half of these patients will still relapse and succumb to the tumor. This is especially true for those patients who were diagnosed to have stage IV neuroblastoma after 1 year of age. The major obstacle to curing these patients derives from refractory microscopic disease. A promising approach is immunotherapy targeting a tumor associated antigen, GD2, which has been shown to be uniformly expressed by neuroblastoma, some melanomas, brain tumors, small cell carcinomas of the lung, 12 and some sarcomas.13 In normal human tissues, GD2 expression is restricted in neuroblastoma and restricted distribution in normal tissues makes anti-GD2 monoclonal antibodies (mabs) suitable for tumor targeted immunotherapy. Clinical trials with anti-tumor mabs suggest that mabs specific for GD2 may be useful in passive immunotherapy of cancer. The primary purpose is to determine if the monoclonal antibody Ch14.18 + cytokines +13-cis-retinoic acid (RA) improves event free survival and overall survival after myeloablative therapy and stem cell rescue as compared to RA alone, in high risk neuroblastoma patients who have achieved a pre-ASCT response.