GD2/CD70 Bi-specific CAR-T Cells for Cancer Treatment
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Number of patients with adverse events.
研究概览
简要总结
The purpose of this study is to assess the feasibility, safety and efficacy of GD2/CD70 bi-specific CAR-T cell therapy in patients with GD2 and/or CD70 positive tumor. Another goal of the study is to learn more about the function of the GD2/CD70 bi-specific CAR-T cells and their persistency in 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.
Patients with refractory and/or recurrent cancer may 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 anti-GD2/CD70 bi-specific chimeric antigen receptor (bi-4SCAR-GD2/CD70). The chimeric antigen receptor (CAR) molecules enable the T cells to recognize and kill target cells through the recognition of a surface antigen, GD2 or CD70, which is expressed at high levels on cancer 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.
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 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with tumors received standard first-line therapy and judged to be non-resectable, metastatic, progressive or recurrent.
- •The expression status of GD2 or CD70 antigens in the tumor tissue will be determined for eligibility. Positive expression is defined by GD2 and PMSA 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.
排除标准
- •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 CD70-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.
研究组 & 干预措施
bi-4SCAR-GD2/CD70 T Cell Therapy for GD2 and/or CD70 positive tumor
干预措施: bi-4SCAR GD2/CD70 T cells (Biological)
结局指标
主要结局
Number of patients with adverse events.
时间窗: 6 months
Determine the toxicity profile the bi-4SCAR GD2/CD70 cells with Common Toxicity Criteria for Adverse Effects version 4.0
次要结局
- The expansion of bi-4SCAR GD2/CD70 T cells(1 year)
- The persistence of bi-4SCAR GD2/CD70 T cells(1 year)
- Anti-tumor effects(1 year)
- Survival time of the patients(3 years)