Phase II Study of Metastatic Melanoma Using Lymphodepleting Conditioning Followed by Infusion of Anti-gp100:154-162 TCR-Gene Engineered Lymphocytes and ALVAC Virus Immunization
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Number of Participants With Metastatic Melanoma Who Develop Clinical Tumor Regression (CR or PR)
研究概览
简要总结
Background:
- gp100 is a protein that is often found in melanoma tumors.
- An experimental procedure developed for treating patients with melanoma uses anti-gp100 cells designed to destroy their tumors. The anti-gp100 cells are created in the laboratory using the patient's own tumor cells or blood cells.
- The treatment procedure also uses a vaccine called plaque purified canarypox vector (ALVAC) gp100, made from a virus that ordinarily infects canaries and is modified to carry a copy of the gp100 gene. The virus cannot reproduce in mammals, so it cannot cause disease in humans. When the vaccine is injected into a patient, it stimulates cells in the immune system that may increase the efficiency of the anti gp 100 cells.
Objectives:
-To evaluate the safety and effectiveness of anti-gp100 cells and the ALVAC gp100 vaccine in treating patients with advanced melanoma.
Eligibility:
-Patients with metastatic melanoma for whom standard treatments have not been effective.
Design:
- Patients undergo scans, x-rays and other tests and leukapheresis to obtain white cells for laboratory treatment.
- Patients have 7 days of chemotherapy to prepare the immune system for receiving the gp100 cells.
- Patients receive the ALVAC vaccine, anti-gp100 cells and interleukin-2 (IL-2) (an approved treatment for advanced melanoma). The anti gp100 cells are given as an infusion through a vein. The vaccine is given as injections just before the infusion of gp100 cells and again 2 weeks later. IL-2 is given as a 15-minute infusion every 8 hours for up to 5 days after the cell infusion for a maximum of 15 doses.
- After hospital discharge, patients return to the clinic for periodic follow-up with a physical examination, review of treatment side effects, laboratory tests and scans every 1 to 6 months.
详细描述
Background:
- We have engineered human peripheral blood lymphocytes (PBLs) to express a T-cell receptor that recognizes an human leukocyte antigens (HLAA) 0201 restricted epitope derived from the gp100 protein.
- We constructed a single retroviral vector that contains both alpha and infinity chains and can mediate genetic transfer of this T cell receptor (TCR) with high efficiency (greater than 30 percent) without the need to perform any selection.
- In co-cultures with HLA-A 0201 positive melanoma gp100:154-162 TCR transduced T cells secreted significant amount of interferon (IFN)-(but no significant secretion was observed in control co-cultures with cell lines.
gp100:154-162 TCR transduced PBL could efficiently kill -HLA-A 0201 positive tumors. There was little or no recognition of normal fibroblasts cells.
- This TCR is over 10 times more reactive with melanoma cells than the melanoma antigen recognized by T-cells (MART)-1 TCR that mediated tumor regression in two patients with metastatic melanoma.
- In this trial we would like to test our hypothesis that the addition of an anti-tumor ALVAC vaccine will result in clinical tumor regression, and persistence of the transferred cells (as is the case in murine models).
Objectives:
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 —（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
ALVAC plus anti-gp100:154-162 TCR PBL + HD IL-2
ALVAC plus anti-gp100:154-162 T cell receptor (TCR) peripheral blood lymphocytes (PBL) + high dose (HD) interleukin-2 (IL-2): ALVAC vaccine two hours prior to cell infusion patients will receive 0.5 ml containing a target dose of 10^7 cell culture infectious dose 50% (CCID50) (with a range of approximately 10^6.4 to 107.9/mL of the gp100 ALVAC virus subcutaneously in each extremity (total of 4 x 10^7 CCID50/2mL. This will be repeated on day 14.
Aldesleukin (IL2, Proleukin, Recombinant human interleukin 2)- 720,000 IU/kg intravenous over 15 minutes every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum 15 doses)
干预措施: cyclophosphamide (Drug)
ALVAC plus anti-gp100:154-162 TCR PBL + HD IL-2
ALVAC plus anti-gp100:154-162 T cell receptor (TCR) peripheral blood lymphocytes (PBL) + high dose (HD) interleukin-2 (IL-2): ALVAC vaccine two hours prior to cell infusion patients will receive 0.5 ml containing a target dose of 10^7 cell culture infectious dose 50% (CCID50) (with a range of approximately 10^6.4 to 107.9/mL of the gp100 ALVAC virus subcutaneously in each extremity (total of 4 x 10^7 CCID50/2mL. This will be repeated on day 14.
Aldesleukin (IL2, Proleukin, Recombinant human interleukin 2)- 720,000 IU/kg intravenous over 15 minutes every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum 15 doses)
干预措施: fludarabine phosphate (Drug)
ALVAC plus anti-gp100:154-162 TCR PBL + HD IL-2
ALVAC plus anti-gp100:154-162 T cell receptor (TCR) peripheral blood lymphocytes (PBL) + high dose (HD) interleukin-2 (IL-2): ALVAC vaccine two hours prior to cell infusion patients will receive 0.5 ml containing a target dose of 10^7 cell culture infectious dose 50% (CCID50) (with a range of approximately 10^6.4 to 107.9/mL of the gp100 ALVAC virus subcutaneously in each extremity (total of 4 x 10^7 CCID50/2mL. This will be repeated on day 14.
Aldesleukin (IL2, Proleukin, Recombinant human interleukin 2)- 720,000 IU/kg intravenous over 15 minutes every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum 15 doses)
干预措施: Aldesleukin (Biological)
ALVAC plus anti-gp100:154-162 TCR PBL + HD IL-2
ALVAC plus anti-gp100:154-162 T cell receptor (TCR) peripheral blood lymphocytes (PBL) + high dose (HD) interleukin-2 (IL-2): ALVAC vaccine two hours prior to cell infusion patients will receive 0.5 ml containing a target dose of 10^7 cell culture infectious dose 50% (CCID50) (with a range of approximately 10^6.4 to 107.9/mL of the gp100 ALVAC virus subcutaneously in each extremity (total of 4 x 10^7 CCID50/2mL. This will be repeated on day 14.
Aldesleukin (IL2, Proleukin, Recombinant human interleukin 2)- 720,000 IU/kg intravenous over 15 minutes every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum 15 doses)
干预措施: ALVAC gp100 Vaccine (Biological)
结局指标
主要结局
Number of Participants With Metastatic Melanoma Who Develop Clinical Tumor Regression (CR or PR)
时间窗: 4-6 weeks after treatment and then monthly for approximately 3 to 4 months or until off study criteria are met
Clinical tumor response is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v.1.0 criteria. Complete response (CR) is a disappearance of all target lesions. Partial response (PR) is a 30% decrease in lesions taking as reference the baseline sum longest diameter (LD). For details about the RECIST criteria see the protocol link module.
次要结局
- Number of Participants With Adverse Events(18.5 months)
- Number of Participants Who Develop Anti-mouse T Cell Receptor (TCR) Antibodies(1 month)
- Number of Participants With in Vivo Survival of T-cell Receptor (TCR) Gene-engineered Cells.(1 month)
研究者
Steven Rosenberg, M.D.
Principal Investigator
National Institutes of Health Clinical Center (CC)