A Pilot Study of the Adoptive Transfer of MART1/Melan-A CTL for Malignant Melanoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Describe the toxicity of two dose levels of adoptively transferred MART1/Melan-A specific CTL lines
研究概览
简要总结
RATIONALE: Cytotoxic T lymphocytes (CTL) are cells of the immune system that can fight infections and cancer. These CTL can be manipulated in the laboratory so that they can target an individual's cancer.
PURPOSE: This early phase trial is studying the feasibility and side effects of intravenous infusions of CTL generated in the laboratory. To produce the CTL, the study participant's own immune cells are collected by a procedure called a leukapheresis. The cells then undergo laboratory processing for three weeks. Part of this processing includes mixing the patients immune cells with a new kind of cell that has some extra genes added to it. These extra genes are to "teach" the participant's own immune cells to become anti-tumor CTL that can attack the melanoma.
详细描述
DETAILED OUTLINE: This is an early phase pilot/feasibility trial.
Study subjects will be sequentially accrued to three cohorts. Cohorts 1 and 2 will evaluate the safety and feasibility of infusing two different doses of CTL.
- Participants in all cohorts will undergo two CTL infusions 5 weeks apart.
- Procedures performed during the trial will include physical examinations, laboratory tests, delayed hypersensitivity testing, and skin biopsies.
- Between 5 and 8 days after the first CTL infusion, a biopsy or excision of a melanoma lesion may be performed.
- Three leukapheresis procedures will be performed: two to collect peripheral blood for CTL production and one for research purposes at the end of the clinical trial.
- Radiology tests (including CT scans) will be performed prior to infusion and about 4-5 weeks after the second CTL infusion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Patients with metastatic melanoma: Either unresectable Stage III or any Stage IV
- •ECOG of 0 or 1
- •HLA-A*0201 haplotype
- •Baseline tumor biopsy MART1/Melan-A expression present (in >10% of tumor cells)
- •Patient provides consent for all required biopsies
- •Adequate intravenous access for leukapheresis
- •Absolute lymphocyte count >500/ul at least once within 30 days of leukapheresis
- •Life expectancy greater than 4 months in the opinion of the study clinician
- •Negative pregnancy test
排除标准
- •Administration of systemic corticosteroids within 28 days of planned leukapheresis
- •Administration of cytotoxic chemotherapy or anti-tumor immunotherapy within 28 days of planned leukapheresis
- •Administration of radiotherapy within 28 days of planned leukapheresis with the exception of subjects accrued to Cohort 3
- •Active autoimmunity requiring systemic immunosuppressive therapy
- •HIV infection
- •Previous enrollment on this protocol and infusion of MART1/Melan-A CTL
研究组 & 干预措施
Cohort 3
Combination of CTL with GMCSF +/- radiation
干预措施: GM-CSF (Drug)
Cohort 1
Different dose of CTL
干预措施: therapeutic autologous lymphocytes (Biological)
Cohort 1
Different dose of CTL
干预措施: Use of an artificial antigen presenting cell (aAPC) to generate CTL (Genetic)
Cohort 2
Different dose of CTL
干预措施: therapeutic autologous lymphocytes (Biological)
Cohort 2
Different dose of CTL
干预措施: Use of an artificial antigen presenting cell (aAPC) to generate CTL (Genetic)
Cohort 3
Combination of CTL with GMCSF +/- radiation
干预措施: therapeutic autologous lymphocytes (Biological)
Cohort 3
Combination of CTL with GMCSF +/- radiation
干预措施: Use of an artificial antigen presenting cell (aAPC) to generate CTL (Genetic)
Cohort 3
Combination of CTL with GMCSF +/- radiation
干预措施: Irradiation of cutaneous tumor lesion (Radiation)
结局指标
主要结局
Describe the toxicity of two dose levels of adoptively transferred MART1/Melan-A specific CTL lines
时间窗: 2 years
Define the feasibility of combining the infusion of MART1/Melan-A specific CTL with the administration of GM-CSF +/- radiotherapy
时间窗: 2 years
Describe the toxicity of combining the infusion of MART1/Melan-A specific CTL with the administration of GM-CSF +/- radiotherapy
时间窗: 2 years
Define the feasibility of generating large doses of MART1/Melan-A specific CTL following leukapheresis in this patient population
时间窗: 2 years
次要结局
- Evaluate function, phenotype, and trafficking of infused CTL.(2 years)
研究者
Marcus O. Butler, MD
Instructor
Dana-Farber Cancer Institute