Single Arm and Multicenter Clinical Trial to Evaluating the Efficacy and Safety of the Chimeric Antigen Receptor T Cell Immunotherapy (CAR-T) for Relapsed or Refractory Neuroblastoma in Children
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 22
- 试验地点
- 2
- 主要终点
- The overall efficiency of patients with neuroblastoma after autologous CAR-T cell therapy
研究概览
简要总结
This single-arm, multicenter clinical study will treat the patient who have relapsed or refractory neuroblastoma with an infusion of the patient's own T cells that have been genetically modified to express a chimeric antigen receptor(CAR)that will bind to tumour cells modified to express the GD2 protein on the cell surface. The study will determine if these modified T cells help the body's immune system eliminate tumour cells .The trial will also study the safety of treatment for CAR-T, how long CAR-T cells stay in the patient's body and the impact on this treatment for survival.
详细描述
This is a single-arm, multicenter clinical study to evaluate efficacy and safety of chimeric antigen receptor T cell immunotherapy (CAR-T) in the treatment of relapsed or refractory neuroblastoma in children. The study will be conducted using a phaseⅠ/Ⅱdesign the study will have the following sequential phases: part A (screening, leukapheresis,cell product preparation and cytoreductive chemotherapy) and part B (treatment and follow-up). the follow-up period for each participant is approximately 35 months after the final CAR-T infusion. The total duration of the study are expected to be approximately 3 years. A total of 22 patients may be enrolled over a period of 3 years.
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 14 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Up to diagnostic criteria for relapsed or refractory neuroblastoma or high-risk patients，including:
- •Relapsed neuroblastoma : Children diagnosed with neuroblastoma who after standard treatment and remission, present lesions again and cannot reach complete remission with surgery.
- •Refractory neuroblastoma : ① Untreated patients that do not have to reach completes remission after 4 courses of chemotherapy in accordance with standard regimens nor reach complete remission with surgery. ② High-risk patients : Who have cell genetic variation, such as MYCN amplification or bone marrow metastasis.
- •Relapsed or Refractory Neuroblastoma: Target, of which expression may be intervened , discovered with Immunohistochemistry can be selected (GD2 +) (more than 50% of tumor cells is at least 2+ , adopting anti-GD2-mAb14G2a ).
- •Age: 1~14 years old of age at the time of enrollment, male or female.
- •Physical condition is good: ECOG score reaches 0 to 2 points.
- •Body weights greater than or equal to 10 kg.
- •White blood cell counts acuity≥ 1.0 x10^9 / L.
- •Estimated survival times > 90 days.
- •Voluntary participation, good compliance, can cooperate with the experimental observation and signed an informed consent form.
排除标准
- •Positive pregnancy tests.
- •Uncontrolled infection.
- •HIV infection, hepatitis B or C activity period.
- •Patients who need long-term immunosuppressive therapy (Such as allergies, autoimmune diseases, GVHD, etc.)
- •Combined activity of the central nervous system malignant tumor invasion.
- •Abnormal coagulation function, patients with severe thrombosis.
- •Organ failure
- •Heart：class Ⅱ or above.
- •Liver：class Ⅱ or above( Refer to Classification of Wuhan Conference (1983)).
- •Kidney: The second stage of renal insufficiency or above.
- •Lung: class Ⅱdecreased slightly or above.
- •Brain: The central nervous system transfer or have active lesions.
- •Patients who have participated in other clinical trials or other clinical trials in the past 30 days.
- •The researchers believe that the patient is not suitable to participate in the study.
结局指标
主要结局
The overall efficiency of patients with neuroblastoma after autologous CAR-T cell therapy
时间窗: 28d,56d,90d
The overall efficiency will be determined by the evaluation of CT/MRI scans and bone marrow biopsy. Assessment of tumor remission rate according to International Neuroblastoma Response Criteria. The overall efficiency = (complete remission (CR) number + the number of very good partial remission (VGPR) number + partial response (PR) number + mixed reaction (MR) number + no response (NR) number) / total number of cases receiving treatment.
次要结局
- Progression free survival(3 years)
- Overall survival(3 years)
- Patients-based Quality of Life Evaluation(3 years)
- 3°or above incidence rate of serious adverse reaction related to treatment(3 years)