Combination of CARTs, CTLs and DC Vaccines Targeting Melanoma
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 30
- 试验地点
- 2
- 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 combination immunotherapy based on CAR T cells, cytotoxic T lymphocytes (CTLs), and dendritic cell (DC) vaccines modified with GM-CSF and B7-2 (CD86) against melanoma, which targets CAR T specific surface antigens such as GD2, CTL specific antigens such as MAGE-A4, gp100 and a pool of melanoma specific antigens presented by the DCs. Another goal of the study is to learn more about the function and persistence of the CAR T cells and antigen-specific immune effectors 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.
Melanoma, known for having the highest mutation burden among solid tumors, has seen a steady rise in incidence over recent years. Early-stage melanoma can often be treated by surgery. As the tumor invades deeper and cancer cells metastasize, the difficulty of radical surgery increases. Although targeted therapies have significantly improved survival rates for patients with advanced melanoma, the potential for drug resistance remains a significant challenge. In this context, immunotherapy has become a new area of exploration.Therapies such as chimeric antigen receptor (CAR) T cell therapy, cytotoxic T lymphocyte (CTL) therapy, and dendritic cell vaccines have demonstrated promising clinical outcomes across various tumor types. Moreover, clinical trials exploring the application of these immunotherapies for treating melanoma are advancing steadily. Consequently, this study aims to explore a novel approach to melanoma treatment by integrating these three distinct forms of immunotherapy.
CAR T cells are a specialized type of T cells engineered to recognize and eliminate tumor cells by targeting specific surface antigens. The selection of the appropriate target antigens is crucial for the efficacy of CAR T cell therapy. Recent research has identified several promising targets for melanoma treatment, including GD2, CD70, and CSPG4. The choice of target may depend on individual patient characteristics. Among these, GD2 is expressed on the surface of a majority of melanoma cells while being minimally present in normal tissues, making it a favorable target in melanoma treatment.
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
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with melanoma have received standard first-line therapy and have been diagnosed with non-resectable, metastatic, progressive or recurrent conditions.
- •The expression of melanoma specific antigens is immunohistochemically stained and verified.
- •Body weight greater than or equal to 40 kg.
- •Age: ≥18 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.
- •Participants 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 any biologic agent, targeted agent, tyrosine kinase inhibitor or metronomic non-myelosuppressive regimen.
- •At least 4 weeks must have elapsed since prior therapy that includes a monoclonal antibody.
- •At least 1 week must has elapsed since any radiation therapy at the time of study entry.
- •Karnofsky/jansky score of 70% 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 ULN.
- •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, the patients or their 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 4 weeks following completion of therapy are eligible.
- •Previous treatment with other genetically engineered 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 availability of T cells.
研究组 & 干预措施
CAR T/CTL/DCvac cells to treat melanoma
Antigen-specific CAR T, CTL and DCvac to treat melanoma.
干预措施: Antigen-specific CAR T, CTL and DCvac to treat melanoma. (Biological)
结局指标
主要结局
Number of patients with adverse events
时间窗: 1 year
The toxicity profile of CAR T, CTL or DCvac is determined by Common Toxicity Criteria for Adverse Effects version 4.0
次要结局
- Anti-tumor effects(1 year)
- The expansion and persistency of antigen-specific CAR T cells(1 year)
- Immune responses after CAR T and CTL infusions and DCvac injections(1 year)
- Survival time of the patients(3 years)