An Open Clinical Study on the Safety and Efficacy of Autologous GD2-CAR T Cells in the Treatment of Relapsed Refractory Neuroblastoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Number of Adverse Events
研究概览
简要总结
Neuroblastoma (NB) is a malignant tumor of the sympathetic nervous system.Chemotherapy and autologous hematopoietic stem cell transplantation are the main treatments for neuroblastoma, and the prognosis of patients with high-risk recurrence and refractory treatment is very poor. There is a large unmet medical need in patients with relapsed refractory neuroblastoma, and further research into new therapeutic approaches is needed for these patients.GD2 is a dissialic ganglioside expressed by neuroectodermal tumors. The proportion of GD2 expression in neuroblastoma is up to 100%, so GD2 is a specific target for neuroblastoma immunotherapy and an ideal target for CAR-T treatment of neuroblastoma.
详细描述
The subjects received the target dose of GD2-CAR-T from 1×106 to 1×108 /kg. Each subject will start with a low dose of 1×106/kg and if there are no significant side effects will be increased to the next dose until the maximum tolerated dose is reached. A variety of adverse events (including neurological events, hematological events, infections, and secondary tumors) will be collected from the time of infusion of CAR T cells to 24 months after infusion. To understand the complete response rate (CR) and partial response rate (PR) at 3 months; Recurrence rate, progression-free survival (PFS) and overall survival (OS) after 1 to 5 years of GD2-CAR-T reinfusion; The amount and duration of GD2-CAR-T in vivo.
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 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All cases were diagnosed as neuroblastoma with positive expression of GD2 antigen in tumor cells. Informed consent of patient or guardian.
- •Diagnosis of recurrent/refractory neuroblastoma.
- •At least 2 weeks or 5 half-lives (whichever is shorter) from the beginning of preconditioning chemotherapy after prior systemic treatment.
- •Toxic reactions caused by previous antitumor therapy must be stabilized and restored to ≤ grade
- •Over 1 years old, under 18 years old.
- •Physical strength score 0-3 (ECOG standard).
- •No obvious active infection.
- •Expected survival ≥3 months
- •Adequate kidney, liver, lung and heart function, defined as creatinine clearance (estimated by the Cockcroft Gault formula) > 60 mL/min; Serum ALT/AST ≤ 2.5 ULN; Total bilirubin ≤1.5 ULN, excluding subjects with Gilbert's syndrome; Cardiac ejection fraction ≥ 50%, echocardiography confirmed centropericardial effusion, and ECG showed no clinically significant abnormal findings. There was no clinically significant pleural effusion. Baseline blood oxygen saturation under indoor ventilation was > 92%.
- •The serum pregnancy test results of fertile women must be negative (women who have undergone surgical sterilization or at least 2 years after menopause are considered to be infertile).
排除标准
- •The subject has had other malignancies, non-melanoma skin tumors, carcinoma in situ (e.g. Cervix, bladder, breast), unless disease-free survival of at least 3 years.
- •There is an uncontrollable infection, including fungal, bacterial, viral or other.
- •Known human immunodeficiency virus (HIV) infection.
- •Known history of hepatitis B (HBsAg positive) or hepatitis C (HCV antibody positive). Subjects with latent or prehepatitis B infection (defined as HBcAb positive and HBsAg negative) can be enrolled only if PCR tests for HBV DNA are negative. In addition, these subjects were required to undergo a monthly PCR test for HBV DNA. Participants who are serologically positive for HCV antibodies can also be enrolled if their PCR test results for HCV RNA are negative.
- •Existing or past CNS disease, such as seizures, cerebrovascular ischemia/bleeding, dementia, cerebellar disease, or any CNS-related autoimmune disease.
- •Serious heart disease, such as uncontrolled or symptomatic arrhythmia, congestive heart failure, or myocardial infarction within 6 months prior to screening, or any grade 3 (moderate) or 4 (severe) heart disease (according to the New York Heart Society Functional Grading Method NYHA).
- •A history of myocardial infarction, angioplasty or stent placement, unstable angina pectoris, or other clinically significant heart disease in the 12 months prior to enrollment.
- •Any medical condition that may affect the evaluation of safety or efficacy.
- •Have had severe rapid hypersensitivity reactions to any of the drugs to be used in this study.
- •Live vaccine should be administered within ≤6 weeks before starting the pretreatment regimen.
- •Pregnant or lactating female subjects.
- •Male or female subjects who do not consent to effective contraception from the time they sign informed consent until 6 months after completing immune cell therapy.
- •Subjects judged by the investigator had difficulty in completing all visits or procedures required by the study protocol (including follow-up visits), or were not compliant enough to participate in the study.
研究组 & 干预措施
Experimental group
GD2 positive relapsed or refractory neuroblastoma
干预措施: GD2-CAR-T cell (Biological)
结局指标
主要结局
Number of Adverse Events
时间窗: 24 months
Adverse events are evaluated with CTCAE V4.03
Overall response rate (ORR)
时间窗: 24 months
ORR includes CR, PR,MR.SD,PD.Complete response (CR)#All components CR.Partial response (PR)#PR in at least one component and all other components CR,minimal disease (bone marrow), PR or not involved at baseline.Minor response (MR)#PR or CR in at least one component but at least one other component with SD; no component with PD.Stable disease (SD)#SD in one component with no better than SD or not involved at baseline in any other component, no component with PD.Progressive disease (PD)#Any component with PD.
次要结局
- Duration of overall response (DOR)(24 months)
- Progression-free survival(PFS)(24 months)
- Overall survival(OS)(24 months)