A Pilot Study of the Administration of Young Tumor Infiltrating Lymphocytes Following a Non-Myeloablative Lymphocyte Depleting Chemotherapy Regimen in Metastatic Melanoma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Objective Response in Patients With Metastatic Melanoma
研究概览
简要总结
Background:
- The National Cancer Institute (NCI) Surgery Branch has developed an experimental therapy that involves taking white blood cells from patients' tumors, growing them in the laboratory in large numbers, and then giving the cells back to the patient with aldesleukin (IL-2) a drug that keeps the white blood cells active. These cells are called Tumor Infiltrating Lymphocytes, or TIL and we have given this type of treatment to over 200 patients with melanoma.
- This study will use chemotherapy to prepare the immune system before this white blood cell treatment. Our prior studies indicate that aldesleukin may not be required for cell transfer.
Objectives:
- To see if chemotherapy and white blood cell therapy without aldesleukin is a safe and effective treatment for metastatic melanoma.
Eligibility:
- Individuals at least 18 years of age and less than or equal to 70 years of age with metastatic melanoma.
Design:
- Work up stage: Patients will be seen as an outpatient at the National Institute of Health (NIH) clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed.
- Surgery: If the patients meet all of the requirements for the study they will undergo surgery to remove a tumor that can be used to grow the TIL product.
- Leukapheresis: Patients may undergo leukapheresis to obtain additional white blood cells. {Leukapheresis is a common procedure, which removes only the white blood cells from the patient.}
- Treatment: Once their cells have grown, the patients will be admitted to the hospital for the conditioning chemotherapy, the TIL cells and aldesleukin. They will stay in the hospital for about 4 weeks for the treatment.
- Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking. Follow up visits will take up to 2 days.
详细描述
BACKGROUND:
- Tumor Infiltrating Lymphocytes (TIL) can mediate the regression of bulky metastatic melanoma when administered to the autologous patient along with high-dose aldesleukin
(IL-2) following a non-myeloablative lymphodepleting chemotherapy preparative regimen.
- IL-2 administration has been shown to increase the number of T regulatory cells and in our trials we have found a direct relationship between the number of IL-2 doses and the reconstitution of patients at one week with cluster of differentiation 4 + forkhead box P3 (CD4+ Foxp3) + T regulatory cells.
- In our analysis of factors that relate to the ability of this treatment to mediate objective responses, we have found a highly significant inverse correlation between reconstitution of CD4+ Foxp3+ T regulatory cells and the likelihood of achieving an objective response.
- In our prior clinical trials of cell transfer using TIL after lymphodepletion with or without
2 (gray)Gy total body irradiation, patients who experienced an objective response received fewer doses of IL-2 compared to non-responders (p=0.007 and 0.03 respectively).
- High levels of the homeostatic T cell growth factor, IL-15, are present in patient serum after the lymphodepleting regimen at the time of cell transfer.
- These factors raise the possibility that IL-2 administration is not required after cell transfer.
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 70 Years（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
Immunotherapy for Metastatic Melanoma
Patients will receive non-myeloablative lymphodepleting preparative regimen cons
干预措施: Cyclophosphamide (Drug)
Immunotherapy for Metastatic Melanoma
Patients will receive non-myeloablative lymphodepleting preparative regimen cons
干预措施: Fludarabine (Drug)
Immunotherapy for Metastatic Melanoma
Patients will receive non-myeloablative lymphodepleting preparative regimen cons
干预措施: Young Tumor Infiltrating Lymphocytes (TIL) (Biological)
结局指标
主要结局
Objective Response in Patients With Metastatic Melanoma
时间窗: Approximately 2 Years
Response is determined 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 the 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
- Level of Persistence of the Transferred Cells in Blood(Once week and one month after transfer)
研究者
Steven Rosenberg, M.D.
Principal Investigator
National Institutes of Health Clinical Center (CC)