NCT00509496终止2 期
Phase II Study of Metastatic Melanoma Using Lymphodepleting Conditioning Followed by Infusion of Anti-gp100:154-162 TCR-Gene Engineered Lymphocytes
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 21
- 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, human leukocyte antigen (HLA-A*0201) derived from the gp100 protein. A retroviral vector was constructed that can deliver the TCR to cells.
- This gene-engineered cell is over 10 times more reactive with melanoma cells than is the melanoma antigen recognized by T-cells (MART-1) TCR that resulted in tumor shrinkage for two patients with metastatic melanoma.
Objectives:
- To determine whether an anti-melanoma protein receptor 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-gp100 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-gp100. Patients receive an IV infusion of the treated cells containing anti-gp100 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 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 tumor infiltrating lymphocytes (TIL) and peripheral blood lymphocytes (PBLs) to express a T-cell receptor that recognizes an HLAA 0201 restricted epitope derived from the gp100 protein.
- We constructed a single retroviral vector that contains both Alpha and Beta chains and can mediate genetic transfer of this TCR with high efficiency (greater than 30 percent) without the need to perform any selection.
- In co-cultures with HLA-A*0201 positive melanoma gp100:154-162 TCR transduced T cells secreted significant amount of IFN-Beta (but no significant secretion was observed in control co-cultures with cell lines.
- gp100:154-162 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-gp100:154-162 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
- Parallel
- 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-gp100:154-162 TCR PBL + HD IL-2
Experimental
- fludarabine phosphate-25 mg/m^2/day intravenous piggy back over 30 minutes for 5 days
- cyclophosphamide-60 mg/kg/day x 2 days intravenous
- Anti-gp100:154-162 TCR-engineered peripheral blood lymphocyte (PBL) cell preparation - minimum of approximately 5 X 10^8 cells and up to 3 x10^11 anti-gp100:154-162 TCR engineered TIL or PBL. The cells are infused intravenously over 20-30 minutes.
- aldesleukin-720,000 IU/kg intravenously over 15 minutes every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses)
干预措施: fludarabine phosphate (Drug)
anti-gp100:154-162 TCR PBL + HD IL-2
Experimental
- fludarabine phosphate-25 mg/m^2/day intravenous piggy back over 30 minutes for 5 days
- cyclophosphamide-60 mg/kg/day x 2 days intravenous
- Anti-gp100:154-162 TCR-engineered peripheral blood lymphocyte (PBL) cell preparation - minimum of approximately 5 X 10^8 cells and up to 3 x10^11 anti-gp100:154-162 TCR engineered TIL or PBL. The cells are infused intravenously over 20-30 minutes.
- aldesleukin-720,000 IU/kg intravenously over 15 minutes every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses)
干预措施: cyclophosphamide (Drug)
anti-gp100:154-162 TCR PBL + HD IL-2
Experimental
- fludarabine phosphate-25 mg/m^2/day intravenous piggy back over 30 minutes for 5 days
- cyclophosphamide-60 mg/kg/day x 2 days intravenous
- Anti-gp100:154-162 TCR-engineered peripheral blood lymphocyte (PBL) cell preparation - minimum of approximately 5 X 10^8 cells and up to 3 x10^11 anti-gp100:154-162 TCR engineered TIL or PBL. The cells are infused intravenously over 20-30 minutes.
- aldesleukin-720,000 IU/kg intravenously over 15 minutes every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses)
干预措施: aldesleukin (Biological)
anti-gp100:154-162 TCR TIL + HD IL-2
Experimental
- fludarabine phosphate-25 mg/m^2/day intravenous piggy back over 30 minutes for 5 days
- cyclophosphamide-60 mg/kg/day x 2 days intravenous
- Anti-gp100:154-162 TCR-engineered tumor infiltrating lymphocytes (TIL) cell preparation- minimum of approximately 5 X 10^8 cells and up to 3 x10^11 anti-gp100:154-162 TCR engineered TIL or PBL. The cells are infused intravenously over 20-30 minutes
- aldesleukin-720,000 IU/kg intravenously over 15 minutes every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses)
干预措施: fludarabine phosphate (Drug)
anti-gp100:154-162 TCR TIL + HD IL-2
Experimental
- fludarabine phosphate-25 mg/m^2/day intravenous piggy back over 30 minutes for 5 days
- cyclophosphamide-60 mg/kg/day x 2 days intravenous
- Anti-gp100:154-162 TCR-engineered tumor infiltrating lymphocytes (TIL) cell preparation- minimum of approximately 5 X 10^8 cells and up to 3 x10^11 anti-gp100:154-162 TCR engineered TIL or PBL. The cells are infused intravenously over 20-30 minutes
- aldesleukin-720,000 IU/kg intravenously over 15 minutes every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses)
干预措施: cyclophosphamide (Drug)
anti-gp100:154-162 TCR TIL + HD IL-2
Experimental
- fludarabine phosphate-25 mg/m^2/day intravenous piggy back over 30 minutes for 5 days
- cyclophosphamide-60 mg/kg/day x 2 days intravenous
- Anti-gp100:154-162 TCR-engineered tumor infiltrating lymphocytes (TIL) cell preparation- minimum of approximately 5 X 10^8 cells and up to 3 x10^11 anti-gp100:154-162 TCR engineered TIL or PBL. The cells are infused intravenously over 20-30 minutes
- aldesleukin-720,000 IU/kg intravenously over 15 minutes every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses)
干预措施: aldesleukin (Biological)
结局指标
主要结局
Clinical Tumor Regression.
时间窗: 20 months
Clinical tumor regression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is a 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 (SD)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(6 years)
研究者
研究点 (1)
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