Treatment of Patients With Metastatic Melanoma Using a Transplant of Autologous Lymphocytes Reactive With Tumor Following a Myeloablative Lymphocyte Depleting Regimen of Chemotherapy, Total Body Irradiation and Reconstitution With CD34+ Cells
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 34
- 试验地点
- 2
- 主要终点
- Clinical Tumor Regression
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide and fludarabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Biological therapies, such as cellular adoptive immunotherapy, work in different ways to stimulate the immune system and stop tumor cells from growing. Autologous stem cell transplant may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy. Interleukin-2 may stimulate a person's lymphocytes to kill tumor cells. Combining chemotherapy, radiation therapy, and biological therapy may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving cyclophosphamide and fludarabine together with radiation therapy followed by cellular adoptive immunotherapy, autologous stem cell transplant, and interleukin-2 works in treating patients with metastatic melanoma.
详细描述
OBJECTIVES:
Primary
- Determine complete clinical tumor regression in patients with metastatic melanoma treated with a myeloablative lymphoid-depleting preparative regimen comprising cyclophosphamide, fludarabine, and total body irradiation followed by autologous tumor-reactive tumor-infiltrating lymphocyte infusion, autologous CD34+ stem cell transplantation, and low-dose or high-dose interleukin-2.
- Evaluate the safety of this regimen in these patients.
Secondary
- Determine the survival of the infused lymphocytes by analyzing the sequence of the variable region of the T-cell receptor or flow cytometry in patients treated with this regimen.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
TBI 200cGy + TIL +HD IL-2, prior IL-2
Patients will receive 2Gy of total body irradiation (TBI) at a rate of 0.07 Gy/minute using a linear accelerator.
Lymphocytes that that are isolated from the tumor, grown in the laboratory to high amounts and then infused into the patient.
干预措施: aldesleukin (Biological)
TBI 200cGy + TIL +HD IL-2, prior IL-2
Patients will receive 2Gy of total body irradiation (TBI) at a rate of 0.07 Gy/minute using a linear accelerator.
Lymphocytes that that are isolated from the tumor, grown in the laboratory to high amounts and then infused into the patient.
干预措施: filgrastim (Biological)
TBI 200cGy + TIL +HD IL-2, prior IL-2
Patients will receive 2Gy of total body irradiation (TBI) at a rate of 0.07 Gy/minute using a linear accelerator.
Lymphocytes that that are isolated from the tumor, grown in the laboratory to high amounts and then infused into the patient.
干预措施: therapeutic tumor infiltrating lymphocytes (Biological)
TBI 200cGy + TIL +HD IL-2, prior IL-2
Patients will receive 2Gy of total body irradiation (TBI) at a rate of 0.07 Gy/minute using a linear accelerator.
Lymphocytes that that are isolated from the tumor, grown in the laboratory to high amounts and then infused into the patient.
干预措施: cyclophosphamide (Drug)
TBI 200cGy + TIL +HD IL-2, prior IL-2
Patients will receive 2Gy of total body irradiation (TBI) at a rate of 0.07 Gy/minute using a linear accelerator.
Lymphocytes that that are isolated from the tumor, grown in the laboratory to high amounts and then infused into the patient.
干预措施: fludarabine phosphate (Drug)
TBI 200cGy + TIL +HD IL-2, prior IL-2
Patients will receive 2Gy of total body irradiation (TBI) at a rate of 0.07 Gy/minute using a linear accelerator.
Lymphocytes that that are isolated from the tumor, grown in the laboratory to high amounts and then infused into the patient.
干预措施: radiation therapy (Radiation)
TBI 200cGy + TIL +HD IL-2, No prior IL-2
Patients will receive 2Gy of total body irradiation (TBI) at a rate of 0.07 Gy/minute using a linear accelerator.
Lymphocytes that that are isolated from the tumor, grown in the laboratory to high amounts and then infused into the patient.
干预措施: aldesleukin (Biological)
TBI 200cGy + TIL +HD IL-2, No prior IL-2
Patients will receive 2Gy of total body irradiation (TBI) at a rate of 0.07 Gy/minute using a linear accelerator.
Lymphocytes that that are isolated from the tumor, grown in the laboratory to high amounts and then infused into the patient.
干预措施: filgrastim (Biological)
TBI 200cGy + TIL +HD IL-2, No prior IL-2
Patients will receive 2Gy of total body irradiation (TBI) at a rate of 0.07 Gy/minute using a linear accelerator.
Lymphocytes that that are isolated from the tumor, grown in the laboratory to high amounts and then infused into the patient.
干预措施: therapeutic tumor infiltrating lymphocytes (Biological)
TBI 200cGy + TIL +HD IL-2, No prior IL-2
Patients will receive 2Gy of total body irradiation (TBI) at a rate of 0.07 Gy/minute using a linear accelerator.
Lymphocytes that that are isolated from the tumor, grown in the laboratory to high amounts and then infused into the patient.
干预措施: cyclophosphamide (Drug)
TBI 200cGy + TIL +HD IL-2, No prior IL-2
Patients will receive 2Gy of total body irradiation (TBI) at a rate of 0.07 Gy/minute using a linear accelerator.
Lymphocytes that that are isolated from the tumor, grown in the laboratory to high amounts and then infused into the patient.
干预措施: fludarabine phosphate (Drug)
TBI 200cGy + TIL +HD IL-2, No prior IL-2
Patients will receive 2Gy of total body irradiation (TBI) at a rate of 0.07 Gy/minute using a linear accelerator.
Lymphocytes that that are isolated from the tumor, grown in the laboratory to high amounts and then infused into the patient.
干预措施: radiation therapy (Radiation)
结局指标
主要结局
Clinical Tumor Regression
时间窗: Every 4-6 weeks for up to 1 year, and then every 6 months for up to 5 years.
Tumor regression is defined as a complete response (CR) or partial response (PR) and was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is the disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD.
Safety
时间窗: 4 years
Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.
次要结局
未报告次要终点
研究者
Steven Rosenberg, M.D.
Principal investigator
National Institutes of Health Clinical Center (CC)