Phase II Study of Metastatic Melanoma Using Lymphodepleting Conditioning Followed by Infusion of Anti-MART-1 F5 TCR-Gene Engineered Lymphocytes
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Clinical Tumor Regression.
研究概览
简要总结
Background:
- Human peripheral blood lymphocytes have been engineered to express a T-cell receptor (TCR) that recognizes a blood type,HLA-A 0201 (human leukocyte antigen) derived from the gp100 protein. A retroviral vector was constructed that can deliver the T-cell receptor (TCR) to cells.
- Patients' cells will be converted into cells able to recognize and fight melanoma tumors.
Objectives:
- To determine whether TCR-engineered lymphocytes can be put in cells removed from patients' tumors or blood and then reinfused, with the purpose of shrinking tumors.
- To evaluate safety and effectiveness of the treatment.
Eligibility:
- Patients 18 years of age or older with metastatic cancer melanoma (cancer that has spread beyond the original site).
- Patient's leukocyte antigen type is HLA-A 0201.
Design:
-Patients undergo the following procedures:
- Leukapheresis (on two occasions). This is a method of collecting large numbers of white blood cells. The cells obtained in the first leukapheresis procedure are grown in the laboratory, and the anti-MART-1 protein is inserted into the cells using an inactivated (harmless) virus in a process called retroviral transduction. Cells collected in the second leukapheresis procedure are used to evaluate the effectiveness of the study treatment.
- Chemotherapy. Patients are given chemotherapy through a vein (intravenously, IV) over 1 hour for 2 days to suppress the immune system so that the patient's immune cells do not interfere with the treatment.
- Treatment with anti-melanoma antigen recognized by T-cells (MART)-1. Patients receive an intravenous (IV) infusion of the treated cells containing anti-MART-1 protein, followed by infusions of a drug called IL-2 (aldesleukin), which helps boost the effectiveness of the treated white cells.
- Patients are given support medications to prevent complications such as infections.
- Patients may undergo a tumor biopsy (removal of a small piece of tumor tissue).
- Patients are evaluated with laboratory tests and imaging tests, such as CT (computed tomography) scans, 4 to 6 weeks after treatment and then once a month for 3 to 4 months to determine the response to treatment.
- Patients have blood tests at 3, 6, and 12 months and then annually for 5 years.
详细描述
Background:
- We have engineered human TIL (tumor infiltrating lymphocytes) and peripheral blood lymphocytes (PBLs) to express an anti-MART-1 T-cell receptor that recognizes an HLA-A*0201 restricted epitope derived from the TIL clone DMF5.
- We constructed a single retroviral vector that contains both alpha and beta chains and can mediate genetic transfer of this TCR with high efficiency without the need to perform any selection.
- In co-cultures with HLA-A*0201 positive melanoma, anti-MART-1 F5 TCR transduced T cells secreted significant amount of interferon (IFN)-gamma (but no significant secretion was observed in control co-cultures with cell lines.
- The anti-MART-1 F5 TCR transduced T-cells could efficiently kill HLA-A*0201 positive tumors. There was little or no recognition of normal fibroblasts cells.
- This TCR is over 10 times more reactive with melanoma cells than the MART-1 TCR that mediated tumor regression in two patients with metastatic melanoma.
Objectives:
Primary objectives:
-Determine if the administration of anti-MART-1 F5 TCR -engineered peripheral blood lymphocytes (PBL) or tumor infiltrating lymphocytes (TIL) and aldesleukin to patients following a nonmyeloablative but lymphoid depleting preparative regimen will result in clinical tumor regression in patients with metastatic melanoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
anti-MART-1 F5 TCR PBL + HD IL-2
Patients treated with peripheral blood lymphocytes (PBL)
干预措施: autologous anti-MART-1 F5 T-cell receptor (Biological)
anti-MART-1 F5 TCR PBL + HD IL-2
Patients treated with peripheral blood lymphocytes (PBL)
干预措施: Cyclophosphamide (Drug)
anti-MART-1 F5 TCR PBL + HD IL-2
Patients treated with peripheral blood lymphocytes (PBL)
干预措施: Fludarabine (Drug)
anti-MART-1 F5 TCR PBL + HD IL-2
Patients treated with peripheral blood lymphocytes (PBL)
干预措施: Aldesleukin (Biological)
anti-MART-1 F5 TCR TIL + HD IL-2
Patients treated with TIL (tumor infiltrating lymphocytes).
干预措施: Cyclophosphamide (Drug)
anti-MART-1 F5 TCR TIL + HD IL-2
Patients treated with TIL (tumor infiltrating lymphocytes).
干预措施: Fludarabine (Drug)
anti-MART-1 F5 TCR TIL + HD IL-2
Patients treated with TIL (tumor infiltrating lymphocytes).
干预措施: Aldesleukin (Biological)
anti-MART-1 F5 TCR TIL + HD IL-2
Patients treated with TIL (tumor infiltrating lymphocytes).
干预措施: autologous anti-MART-1 F5 T-cell receptor gene-engineered tumor infiltrating lymphocytes (Biological)
结局指标
主要结局
Clinical Tumor Regression.
时间窗: 7/5/07-4/23/09
Tumor regression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Progressive disease (PD) is at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD.
次要结局
- Toxicity(57 months)