Anti-GD2 4th Generation Chimeric Antigen Receptor-modified T Cells (4SCAR-GD2) Targeting Refractory and/or Recurrent Neuroblastoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Number of patients with adverse events.
研究概览
简要总结
Patients with refractory and/or recurrent neuroblastoma have poor prognosis despite complex multimodel therapy and therefore, novel approaches are urgently needed. The investigators are attempt to treat this disease using T cells genetically modified with a 4th generation lentiviral chimeric antigen receptor (CAR) targeting GD2 (4SCAR-GD2). The 4SCAR-GD2-modified T cells can recognize and kill neuroblastoma through the recognition of GD2, a surface protein expressed at high levels on neuroblastoma but not on normal tissues. This study will evaluate the side effects and effective doses of 4SCAR-GD2 T cells in treating refractory and/or recurrent neuroblastoma.
详细描述
Background:
Patients with refractory and/or recurrent neuroblastoma have poor prognosis despite complex multimodal therapy; therefore, novel curative approaches are needed. The investigators are attempting to use T cells obtained directly from the patient, which can be genetically modified to express a 4th generation GD2-specific chimeric antigen receptor (4SCAR-GD2). The chimeric antigen receptor (CAR) molecules enable the T cells to recognize and kill neuroblastoma through the recognition of a surface antigen, GD2, which is expressed at high levels in neuroblastoma but not at significant levels on normal tissues. This study will evaluate the side effects and the best dose of a novel 4th generation anti-GD2 CAR T cells to refractory and/or recurrent neuroblastoma.
Objectives:
1. Primary: To determine the safety and feasibility of administration of 4SCAR-GD2 T cells to children with neuroblastoma following a cyclophosphamide/fludarabine preparative regimen.
2. Secondary:
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
- •Patients with neuroblastoma have received standard first-line therapy and been judged to be non-resectable, metastatic, progressive/persistent or recurrent.
- •The GD2 antigen status of the neuroblastoma will be determined for eligibility. Positive expression is defined by GD2 antibody staining results based on immunohistochemistry or flow cytometry analyses.
- •Body weight greater than or equal to 10 kg.
- •Age: ≥1 year and ≤ 14 years of age at the time of enrollment.
- •Life expectancy: at least 8 weeks.
- •Prior Therapy: 1) There is no limit to the number of prior treatment regimens. Any grade 3 or 4 non-hematologic toxicity of any previous therapy must have resolved to grade 2 or less. 2) Must not have received hematopoietic growth factors for at least 1 week prior to mononuclear cells collection. 3) At least 7 days must have elapsed since the completion of therapy with a biologic agent, targeted agent, tyrosine kinase inhibitor or a metronomic nonmyelosuppressive regimen. 4) At least 4 weeks must have elapsed since prior therapy that included a monoclonal antibody. 5) At least 1 weeks since any radiation therapy at the time of study entry.
- •Karnofsky/jansky score of 60% or greater.
- •Cardiac function: Left ventricular ejection fraction greater than or equal to 40/55 percent .
- •Pulse Ox greater than or equal to 90% on room air.
- •Liver function: defined as alanine transaminase (ALT) <3x upper limit of normal (ULN), aspartate aminotransferase (AST) <3x ULN; serum bilirubin and alkaline phosphatase <2x ULN.
- •Renal function: Patients must have serum creatinine less than 3 times upper limit of normal.
- •Marrow function: White blood cell count ≥1000/ul, Absolute neutrophil count ≥500/ul, Absolute lymphocyte count ≥500/ul, Platelet count ≥25,000/ul (not achieved by transfusion).
- •Patients with known bone marrow metastatic disease will be eligible for study as long as they meet hematologic function criteria, and the marrow disease not evaluable for hematologic toxicity.
- •Patients must have autologous transduced T cells at levels greater than or equal to 2x10e5 cells per kilogram body weight.
- •For all patients enrolled in this study, their parents or legal guardians must sign an informed consent and assent.
排除标准
- •Existing severe illness (e.g. significant cardiac, pulmonary, hepatic diseases, etc.) or major organ dysfunction, with the exception of grade 3 hematologic toxicity.
- •Untreated central nervous system (CNS) metastasis:
- •Patients with previous CNS tumor involvement that has been treated and is stable for at least 6 weeks following completion of therapy are eligible.
- •Previous treatment with other genetically engineered GD2-CAR T cells.
- •Active HIV, Hepatitis B virus (HBV), Hepatitis C virus (HCV) infection or uncontrolled infection.
- •Patients who require systemic corticosteroid or other immunosuppressive therapy.
- •Patients previously experienced severe toxicity from cyclophosphamide or fludarabine.
- •Evidence of tumor potentially causing airway obstruction.
- •Inability to comply with protocol requirements.
- •Insufficient CAR T cells availability.
研究组 & 干预措施
effectiveness of Anti-GD2 CART
Anti-GD2 CART cells can recognize and kill neuroblastoma through the recognition of GD2. This study will evaluate the side effects and effective doses of Anti-GD2 CART cells in treating refractory and/or recurrent neuroblastoma
干预措施: Anti-GD2 CART (Biological)
结局指标
主要结局
Number of patients with adverse events.
时间窗: 1yr
Determine the toxicity profile of the 4SCAR-GD2-modified T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.
次要结局
- Anti-tumor effects(1yr)
- To evaluate the expansion and persistence of anti-GD2 CAR T cells(1yr)
- Survival time of the patients(1yr)
研究者
Yang Lihua
Associate Director
Zhujiang Hospital