GD2/CD56 Bi-specific CAR-T Cell Therapy
GD2/CD56 Bi-specific CAR-T Cells for Cancer Treatment
研究概览
详细说明
Patients with refractory and/or recurrent malignancies have poor prognosis despite complex multimodal therapy; therefore, novel curative approaches are needed. The investigators attempt to use T cells genetically modified to express a 4th generation lentiviral GD2/CD56 bi-specific chimeric antigen receptor (bi-4SCAR-GD2/CD56). The chimeric antigen receptor (CAR) molecules enable the T cells to recognize and kill tumor cells through the recognition of a surface antigen, GD2 or CD56, which is expressed at high levels on tumor cells but not at significant levels on normal tissues.
Disialoganglioside (GD2) is a well-studied tumor associated antigen which is expressed uniformly in nervous system-related tumors but at low levels in normal tissues. Over the past few years, CAR-T therapy against GD2 in tumor has achieved encouraging but modest outcomes. Only a fraction of patients achieved measurable responses. In solid tumors, GD2 CAR-T therapy alone may not be as effective as CAR-T cell therapy in hematological malignancies.
Similar to GD2, the CD56 antigen (NCAM-1) is highly expressed on malignancies with neuronal or neuroendocrine differentiation, including small-cell lung cancer, glioblastoma and neuroblastoma, tumor types for which new therapeutic options are needed. CD56-CAR-T cell therapy has potential for treating patients with aggressive malignancies that are nonresponsive to conventional radiotherapy and chemotherapy, or are unsuitable for hematopoietic stem cell transplantation.
To overcome tumor escape of single target antigen and enhance in vivo CAR-T efficacy, a novel bi-specific GD2/CD56 CAR-T therapy regimen is developed to include booster and consolidation CAR-T applications to target highly-refractory cancer. The aim is to evaluate safety and long term efficacy of the bi-CAR-T therapy strategy in GD2 and/or CD56 positive cancer patients.
研究类型
注册 (预期的)
阶段
- 阶段2
- 阶段1
联系人和位置
学习地点
-
-
Guangdong
-
Shenzhen、Guangdong、中国、518000
- 招聘中
- Shenzhen Geno-Immune Medical Institute
-
-
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Patients with tumors received standard first-line therapy and have been judged to be non-resectable, metastatic, progressive or recurrent.
- The expression status of GD2 or CD56 antigens in the tumor tissue will be determined for eligibility. Positive expression is defined by GD2 and CD56 antibody staining results based on immunohistochemistry or flow cytometry analyses.
- Body weight greater than or equal to 10 kg.
- Age: ≥1 year and ≤ 75 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 be 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, selected targeted agent 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 does not have hematologic toxicity.
- For all patients enrolled in this study, themselves or their parents or legal guardians must sign an informed consent and assent.
Exclusion Criteria:
- Existing severe illness (e.g. significant cardiac, pulmonary, hepatic diseases, etc.) or major organ dysfunction, or greater than grade 2 hematologic toxicity.
- Untreatable 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 or CD56-specific 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.
- Evidence of tumor potentially causing airway obstruction.
- Inability to comply with protocol requirements.
- Insufficient CAR T cells availability.
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
---|---|
实验性的:bi-4SCAR-GD2/CD56 T Cell Therapy for GD2 and/or CD56 positive tumor
|
Infusion of bi-4SCAR GD2/CD56 T cells at 10^6 cells/kg body weight via IV
|
研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Number of patients with adverse events.
大体时间:6 months
|
Determine the toxicity profile the bi-4SCAR GD2/CD56 cells with Common Toxicity Criteria for Adverse Effects version 4.0
|
6 months
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
抗肿瘤作用
大体时间:1年
|
客观完全缓解 (CR) 通过实体瘤缓解评估标准 (RECIST) v1.1 标准进行评估。
|
1年
|
Anti-tumor effects
大体时间:1 year
|
Objective partial response (PR) are assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
|
1 year
|
The expansion of bi-4SCAR GD2/CD56 T cells
大体时间:1 year
|
Scale of CAR copies
|
1 year
|
The persistence of bi-4SCAR GD2/CD56 T cells
大体时间:1 year
|
Scale of tumor burden (for efficacy)
|
1 year
|
Survival time of the patients
大体时间:3 years
|
The progression free survival (PFS) time of the patients treated with the bi-4SCAR GD2/CD56 T cells will be evaluated
|
3 years
|
Survival time of the patients
大体时间:3 years
|
The overall survival (OS) time of the patients treated with the bi-4SCAR GD2/CD56 T cells will be evaluated
|
3 years
|
合作者和调查者
研究记录日期
研究主要日期
学习开始 (预期的)
初级完成 (预期的)
研究完成 (预期的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.