Phase II Study in Patients With Metastatic Melanoma Using a Non-Myeloablative Lymphocyte Depleting Regimen of Chemotherapy Followed by Infusion of gp100 Reactive Peripheral Blood Lymphocytes (PBL) and High or Low Dose Aldesleukin
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Toxicity as Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V3.0
研究概览
简要总结
Background:
This study uses a new experimental procedure for treating melanoma that uses the patient's own lymphocytes (type of white blood cell), which are specially selected to target and destroy their tumor.
Objectives:
To determine whether this experimental treatment can cause the patient's tumor to shrink.
To test the safety of the treatment and its effects on the immune system.
Eligibility:
Patients with metastatic melanoma 18 years of age and older for whom standard treatments are not effective or who cannot take high-dose interleukin-2 (IL-2).
Patients must have the tissue type human leukocyte antigens (HLA-A)0201.
Design:
Workup: Patients have scans, x-rays, laboratory tests, and other tests as needed.
Patients have leukapheresis (a procedure for collecting lymphocytes that is similar to collecting whole blood) to collect cells for laboratory treatment and later reinfusion.
Chemotherapy: Patients have low-dose chemotherapy for 1 week to prepare the immune system to receive the cultured lymphocytes.
Cell infusion and IL-2 treatment: Patients receive the lymphocytes by infusion through a vein and then either high-dose IL-2 infused through a vein or low-dose IL-2 injected under the skin. High-dose IL-2 is given as infusions through a vein every 8 hours for up to 15 doses. Low-dose IL-2 is given as injections under the skin daily for 5 days, followed by a 2-day rest, with this regimen repeated for a total of 5 weeks.
Recovery: Patients rest for 1 to 2 weeks to recover from the effects of chemotherapy and IL-2.
Tumor biopsy: Patients may be asked to have a biopsy (removal of a small piece of tumor) after receiving treatment to look at the effects of treatment in the tumor.
Follow-up: After treatment is completed, patients return to the clinic for physical examinations, review of side effects, laboratory tests and scans every 1 to 6 months until the disease worsens.
Retreatment: Patients whose tumor did not grow after treatment or showed evidence of shrinking may be able to be retreated if their tumor begins to grow. They receive the same regimen of chemotherapy, lymphocyte infusion and IL-2 treatment....
详细描述
Background:
- Tumor infiltrating lymphocytes (TIL) transfer studies in patients with metastatic melanoma following lymphodepletion have resulted in 50% objective response rates with a 10-15% rate of complete responses.
- Pre-clinical and clinical studies of adoptive immunotherapy have suggested that effective lymphocytes for transfer have high avidity for the target antigen, undergo limited in vitro antigen and IL-2 stimulation, and have high expression of cluster of differentiation 27+ (CD27+).
- We have developed a novel in vitro strategy using high throughput polymerase chain reaction (PCR) screening to rapidly isolate low frequency antigen specific cluster of differentiation 8+ (CD8+) T cells from the peripheral blood repertoire that have these characteristics, and that recognize the gp100:154-162 epitope, an abundantly expressed melanoma antigen, presented by human leukocyte antigens (HLAA2) on the tumor surface.
- The current proposed transfer of gp100:154-162 reactive lymphocytes administered in conjunction with a lymphodepleting preparative regimen and aldesleukin would represent a significantly novel approach to adoptive immunotherapy.
Objectives:
- To determine whether gp100:154-162 reactive cluster of differentiation 4+ (CD4+) T cell depleted lymphocytes infused in conjunction with the administration of high-dose aldesleukin or low-dose aldesleukin may result in clinical tumor regression in patients with metastatic melanoma receiving a non-myeloablative lymphoid depleting preparative regimen.
- To evaluate the safety of the treatment in patients receiving the non-myeloablative conditioning regimen, cell transfer, and high-dose or low-dose aldesleukin.
- To determine the survival in patients, of infused cells following the administration of the non-myeloablative regimen, using analysis of the sequence of the variable region of the T cell receptor or flow cytometry (fluorescence activated cell sorting-FACS).
Eligibility:
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
Cohort I - high dose Aldesleukin
Patients receive high-dose aldesleukin intravenous (IV) over 15 minutes every 8 hours beginning within 24 hours after peripheral blood lymphocyte (PBL) infusion and continuing for up to 5 days (maximum of 15 doses).
干预措施: Aldesleukin (Drug)
Cohort II - low dose Aldesleukin
Beginning within 24 hours after peripheral blood lymphocyte (PBL) infusion, patients receive low-dose aldesleukin subcutaneous (SC) once daily 5 days a week for up to 6 weeks.
干预措施: Aldesleukin (Drug)
结局指标
主要结局
Toxicity as Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V3.0
时间窗: 16 months
Here is the number of participants with adverse events. For a detailed list of participants with adverse events, see the adverse event module.
Response
时间窗: 30 months
Response is 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. Progression (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 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
未报告次要终点
研究者
Udai Kammula, M.D.
Principal Investigator
National Institutes of Health Clinical Center (CC)