A Phase II Study of Cell Transfer Therapy for Metastatic Melanoma Using 41BB Selected Tumor Infiltrating Lymphocytes Plus IL-2 Following a Non-Myeloablative Lymphocyte Depleting Chemotherapy Regimen
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Objective Response Rate of 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. These cells are called Tumor Infiltrating Lymphocytes, or TIL and we have given this type of treatment to over 100 patients. In this study, we are selecting a specific subset of white blood cells from the tumor that we think are the most effective in fighting tumors and will use only these cells in making the tumor fighting cells.
Objective:
The purpose of this study is to see if these specifically selected tumor fighting cells can cause melanoma tumors to shrink and to see if this treatment is safe.
Eligibility:
- Adults age 18-70 with metastatic melanoma who have a tumor that can be safely removed.
Design:
- Work up stage: Patients will be seen as an outpatient at the National Institutes 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 tumor infiltrating lymphocytes (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 take up to 2 days.
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详细描述
Background:
- Autologous tumor infiltrating lymphocytes (TIL) followed by high dose aldesleukin can mediate the regression of bulky metastatic melanoma when administered to a patient following a non-myeloablative but lymphodepleting chemotherapy preparative regimen.
- In animal models, mixing irrelevant (non-reactive) cells with tumor-reactive cells negatively impacts on tumor treatment possibly by competing for cytokines, suggesting that enrichment for tumor-reactive cells could enhance clinical efficacy. Additionally, preclinical animal models and clinical investigation have demonstrated that prolonged in vitro culture negatively impacts on tumor treatment.
- The current method for enrichment of tumor-reactive TIL requires screening of multiple independent TIL cultures for anti-tumor specificity using gamma-interferon production by TIL. However, in vitro screening depends on autologous tumor reagents that are often unavailable, and interferon (IFN) gamma release in vitro may not be the best effector function to evaluate tumor recognition. The screen increases the length of in vitro culture times (30 days), which results in shorter telomere lengths and more differentiated cells. Additionally, selection of a few highly reactive cultures for further expansion may reduce the diversity of cluster of differentiation 8 (CD8+) repertoire recognizing the tumor.
- 4-1BB is a co-stimulatory molecule up-regulated on the cell surface of T cells upon T-cell receptor (TCR) engagement. Pre-clinical studies in the Surgery Branch have evaluated a fast and simplified method to select and expand a diverse tumor-reactive repertoire, regardless of knowledge of the specific antigen recognized, based on selection of 4-1BB expressing TIL from the fresh tumor digest.
Objectives:
- To determine the safety and objective response rate of patients with metastatic melanoma receiving ACT using 4-1BB selected TIL plus aldesleukin treatment following a chemotherapy preparative regimen.
- To determine the survival of patients receiving this treatment regimen.
Eligibility:
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
Lymphocyte Depleting Prep Regimen
Patients will receive a lymphocyte depleting preparative regimen of cyclophosphamide and fludarabine followed by intravenous (IV) infusion of 4-1BB selected tumor infiltrating lymphocytes (TIL) plus IV aldesleukin.
干预措施: Aldesleukin (Drug)
Lymphocyte Depleting Prep Regimen
Patients will receive a lymphocyte depleting preparative regimen of cyclophosphamide and fludarabine followed by intravenous (IV) infusion of 4-1BB selected tumor infiltrating lymphocytes (TIL) plus IV aldesleukin.
干预措施: Fludarabine (Drug)
Lymphocyte Depleting Prep Regimen
Patients will receive a lymphocyte depleting preparative regimen of cyclophosphamide and fludarabine followed by intravenous (IV) infusion of 4-1BB selected tumor infiltrating lymphocytes (TIL) plus IV aldesleukin.
干预措施: Cyclophosphamide (Drug)
Lymphocyte Depleting Prep Regimen
Patients will receive a lymphocyte depleting preparative regimen of cyclophosphamide and fludarabine followed by intravenous (IV) infusion of 4-1BB selected tumor infiltrating lymphocytes (TIL) plus IV aldesleukin.
干预措施: 4-1BB Selected Tumor Infiltrating Lymphocytes (TIL) (Biological)
结局指标
主要结局
Objective Response Rate of Patients With Metastatic Melanoma
时间窗: approximately 2 years
Objective response is defined as complete response + partial response and was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. 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 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.
Count of Participants With Serious and Non-Serious Adverse Events
时间窗: 2 years and 59 days
Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE) v3.0. A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
次要结局
- Overall Survival (OS) of Patients Receiving a Lymphocyte Depleting Preparative Regimen(up to 3 years)
研究者
Steven Rosenberg, M.D.
Principal Investigator
National Institutes of Health Clinical Center (CC)