Multi-center Phase I/II Clinical Trial of 4SCAR-T Therapy Targeting GD2, PSMA and CD276 for Treating Neuroblastoma
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 100
- 试验地点
- 5
- 主要终点
- Number of patients with adverse events
研究概览
简要总结
The purpose of this clinical trial is to assess the feasibility, safety and efficacy of multiple 4SCAR-T cell therapy which targets GD2, PSMA and CD276 surface antigens in patients with relapsed and refractory neuroblastoma (NB). Another goal of the study is to understand the function of the multi-CAR-T cells and their persistency in the patients.
详细描述
Important Regulatory Notice:
This trial record is only for global academic information registration on ClinicalTrials.gov. Neither the sponsor Beijing Meikang Jimian Biotechnology Co., Ltd. nor collaborator Shenzhen Geno-Immune Medical Institute has obtained NMPA clinical trial approval or clinical technology filing permission to carry out interventional cell therapy trials in mainland China.
ClinicalTrials.gov registration alone does not represent legal approval by Chinese health and drug regulatory authorities.
Neuroblastoma is one of the most aggressive childhood tumors arising from neural crest cells. Nearly 50% of patients with high risk disease have poor long-term survival even after multimodal treatments. Novel immunotherapy targeting tumor-specific antigens has been developed to meet the desperate need.
Disialoganglioside (GD2) is a well-studied tumor associated antigen which is expressed uniformly in NB but restrictedly in normal tissue. Over the past few years, CAR-T therapy against GD2 in NB has achieved encouraging but modest outcomes. Only a fraction of patients achieved measurable responses. Like for many other solid tumors, CAR-T therapy for NB is not as effective as for hematologic malignancies.
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 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with tumors have received standard first-line therapy and been judged to be non-resectable, metastatic, progressive or recurrent.
- •The expression status of GD2, PSMA and CD276 antigens of the tumor will be determined for eligibility. Positive expression is defined by GD2, PMSA and CD276 antibody staining results based on immunohistochemistry or flow cytometry analyses.
- •Body weight greater than or equal to 10 kg.
- •Age: ≥1 year and ≤ 65 years of age at the time of enrollment.
- •Life expectancy: at least 8 weeks.
- •Prior Therapy:
- •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.
- •Participant must not have received hematopoietic growth factors for at least 1 week prior to mononuclear cells collection.
- •At least 7 days must have elapsed since the completion of therapy with a biologic agent, targeted agent, tyrosine kinase inhibitor or a metronomic non-myelosuppressive regimen.
- •At least 4 weeks must have elapsed since prior therapy that included a monoclonal antibody.
- •At least 1 week 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.
- •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, PSMA and CD276 CART cells.
- •Active HIV, Hepatitis B virus (HBV), Hepatitis C virus (HCV) infection or uncontrolled infection.
- •Patients who require systemic corticosteroid or other immunosuppressive therapy.
- •Evidence of tumor potentially causing airway obstruction.
- •Inability to comply with protocol requirements.
- •Insufficient CART cells availability.
研究组 & 干预措施
effectiveness of CAR-T cells targeting GD2, PSMA and CD276
Gene-modified T cells are designed to kill tumor cells through specific recognition of GD2, PSMA and CD276. This study will evaluate the side effects and effective doses of GD2, PSMA and CD276 CAR-T cells in treating refractory and recurrent NB
干预措施: GD2, PSMA and CD276 CAR-T cells (Biological)
结局指标
主要结局
Number of patients with adverse events
时间窗: 3 year
Determine the toxicity profile the GD2, PSMA and CD276 4SCAR-T cells with Common Toxicity Criteria for Adverse Effects version 4.0
次要结局
- The anti-tumor activity after CAR-T infusions(1 year)
- Anti-tumor effects(3 year)
- The expansion of CAR-T cells(3 year)
- The cytokine secretion profile after CAR-T infusions(1 year)
- Survival time of the patients(3 year)