A Prospective Randomized Study of Cell Transfer Therapy for Metastatic Melanoma Using Short-Term Cultured Tumor-Infiltrating Lymphocytes Plus IL-2 Following Either a Non-Myeloablative Lymphocyte Depleting Chemotherapy Regimen Alone or in Conjunction With 12Gy Total Body Irradiation (TBI)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 102
- 试验地点
- 1
- 主要终点
- Percentage of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression)
研究概览
简要总结
Background:
- An experimental treatment for metastatic melanoma involves cell therapy, in which researchers take white blood cells (lymphocytes) from the tumor tissue, grow them in the laboratory in large numbers, and then use the cells to attack the tumor tissue. Before receiving the cells, chemotherapy is needed to temporarily suppress the immune system to improve the chances that the tumor-fighting cells will be able to survive in the body. In some studies of cell therapy, individuals who have received total body irradiation (TBI) in addition to the chemotherapy (in order to increase the length of time that they do not produce white blood cells) seem to have a slightly better response to the treatment, but it is not known if adding radiation to the cell therapy will cause a better response for all individuals. Researchers are interested in comparing cell therapy given with the usual chemotherapy to cell therapy given with the usual chemotherapy and TBI.
Objectives:
- To compare the effectiveness of cell therapy given with chemotherapy to cell therapy given with chemotherapy and total body irradiation in individuals with metastatic melanoma.
Eligibility:
- Individuals at least 18 years of age who have been diagnosed with metastatic melanoma.
Design:
- Participants will be screened with a physical examination, medical history, blood tests, and tumor imaging studies.
- Participants will be divided into two groups: cell therapy with chemotherapy alone (group 1) or cell therapy with chemotherapy plus TBI (group 2).
- All participants will provide a tumor sample from either surgery or a tumor biopsy for white blood cell collection.
- Participants will have leukapheresis to collect additional white blood cells for cell growth and future testing, and TBI group participants will also provide stem cells to help them recover after radiation. (TBI participants who cannot provide enough stem cells will be moved to the non-radiation treatment group.)
- Participants will have chemotherapy with cyclophosphamide (two treatments over 2 days) and fludarabine (five treatments over 5 days) starting 7 days before the cell therapy. Participants in the TBI group will also have TBI for the 3 days immediately before the cell therapy.
- All participants will receive the white blood cells, followed by high dose aldesleukin every 8 hours for up to 5 days after the cell infusion to help keep the therapy cells alive and active. Participants will also have injections of filgrastim to stimulate blood cell production, and participants in the TBI group will also receive their stem cells.
- Participants will take an antibiotic for at least 6 months after treatment to prevent pneumonia and will be asked to return for regular monitoring and follow-up visits for at least 5 years to evaluate the tumors response to treatment.
详细描述
Background:
- Adoptive cell therapy (ACT) using autologous tumor infiltrating lymphocytes can mediate the regression of bulky metastatic melanoma when administered along with high-dose aldesleukin (IL-2) following a non-myeloablative lymphodepleting chemotherapy preparative regimen consisting of cyclophosphamide and fludarabine.
- In a series of consecutive trials using this chemotherapy preparative regimen alone or with 2 Gray (Gy) or 12 Gy total body irradiation (TBI) objective response rates using Response Evaluation Criteria in Solid Tumors (RECIST) criteria were 49%, 52%, and 72%, respectively. Complete regression rates in these three consecutive trials were 12%, 20%, and 40%, respectively strongly suggesting that the addition of TBI could improve the complete regression rate. Of the 20 complete regressions seen in this trial, 19 are on-going at 37 to 82 months.
- Because of the complexity of developing selected TIL for use in adoptive transfer, we have recently developed a simplified method for producing TIL that is more applicable to use in outside institutions. Utilizing young TIL cells (sometimes with cluster of differentiation 8 (CD8) purification) in 105 patients, the objective response rate was 34% with a 6.6 % incidence of complete regressions. All patients in this trial received the cyclophosphamide fludarabine regimen alone.
- Because of the strong suggestion that the addition of TBI to the chemotherapy regimen could increase durable, complete regression rates in patients with metastatic melanoma, we are now attempting to definitively determine whether the addition of TBI to the chemotherapy preparative regimen can improve complete response rates, and overall survival in patients receiving young TIL.
Objectives:
-To determine, in a prospective randomized trial, the complete response rate and survival of patients with metastatic melanoma receiving adoptive cell transfer (ACT) using young TIL plus aldesleukin treatment following either a chemotherapy preparative regimen alone, or the same chemotherapy preparative regimen plus TBI.
Eligibility:
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 66 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
Arm 1/Adoptive Cell Therapy (ACT)
Non-myeloablative lymphodepleting preparative regimen of cyclophosphamide and fludarabine + young tumor infiltrating lymphocytes (TIL) + high dose aldesleukin
干预措施: Aldesleukin (Drug)
Arm 1/Adoptive Cell Therapy (ACT)
Non-myeloablative lymphodepleting preparative regimen of cyclophosphamide and fludarabine + young tumor infiltrating lymphocytes (TIL) + high dose aldesleukin
干预措施: Cyclophosphamide (Drug)
Arm 1/Adoptive Cell Therapy (ACT)
Non-myeloablative lymphodepleting preparative regimen of cyclophosphamide and fludarabine + young tumor infiltrating lymphocytes (TIL) + high dose aldesleukin
干预措施: Fludarabine (Drug)
Arm 1/Adoptive Cell Therapy (ACT)
Non-myeloablative lymphodepleting preparative regimen of cyclophosphamide and fludarabine + young tumor infiltrating lymphocytes (TIL) + high dose aldesleukin
干预措施: Young TIL (Biological)
Arm 2/Adoptive Cell Therapy (ACT) + Total Body Irradiation (TBI)
Non-myeloablative lymphodepleting preparative regimen of cyclophosphamide and fludarabine + young tumor infiltrating lymphocytes (TIL) + high dose aldesleukin + total body irradiation (TBI)
干预措施: Aldesleukin (Drug)
Arm 2/Adoptive Cell Therapy (ACT) + Total Body Irradiation (TBI)
Non-myeloablative lymphodepleting preparative regimen of cyclophosphamide and fludarabine + young tumor infiltrating lymphocytes (TIL) + high dose aldesleukin + total body irradiation (TBI)
干预措施: Cyclophosphamide (Drug)
Arm 2/Adoptive Cell Therapy (ACT) + Total Body Irradiation (TBI)
Non-myeloablative lymphodepleting preparative regimen of cyclophosphamide and fludarabine + young tumor infiltrating lymphocytes (TIL) + high dose aldesleukin + total body irradiation (TBI)
干预措施: Fludarabine (Drug)
Arm 2/Adoptive Cell Therapy (ACT) + Total Body Irradiation (TBI)
Non-myeloablative lymphodepleting preparative regimen of cyclophosphamide and fludarabine + young tumor infiltrating lymphocytes (TIL) + high dose aldesleukin + total body irradiation (TBI)
干预措施: Young TIL (Biological)
Arm 2/Adoptive Cell Therapy (ACT) + Total Body Irradiation (TBI)
Non-myeloablative lymphodepleting preparative regimen of cyclophosphamide and fludarabine + young tumor infiltrating lymphocytes (TIL) + high dose aldesleukin + total body irradiation (TBI)
干预措施: Total Body Irradiation (TBI) (Radiation)
结局指标
主要结局
Percentage of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression)
时间窗: Participants were followed from treatment to progression of disease or until principal investigator (PI) discretion (average 91.8 months).
Percentage of participants who have a clinical response to treatment (objective tumor regression) was measured 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 refence 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. The appearance of one or more new lesions is also considered progressions. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum LD.
Overall Survival (OS)
时间窗: Participants were followed from treatment until death (median 14 months) or until principal investigator (PI) discretion (median 99.0 months) for participants alive at study closure.
OS is defined as the time to death following the start of treatment.
次要结局
- Progression-free Survival (PFS)(Participants were followed from treatment until death or until principal investigator (PI) discretion. A median of 91.8 months.)
- Number of Grades 1, 2, 3, 4, and/or 5 Serious Adverse Events Possibly and/or Probably Related to Treatment(Time of registration through 6 years after the last treatment.)
- Number of Grades 1, 2, 3, 4, and/or 5 Non-serious Adverse Events Possibly and/or Probably Related to Treatment(30 days after end of treatment, up to 6 years)
研究者
Steven Rosenberg, M.D.
Principal Investigator
National Cancer Institute (NCI)