NCT01457131终止1 期
Phase I/II Study of Metastatic Cancer That Expresses NY-ESO-1 Using Lymphodepleting Conditioning Followed by Infusion of Gene Engineered Lymphocytes Cotransduced With Genes Encoding IL-12 and Anti-NY ESO-1 TCR
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 2
- 主要终点
- To evaluate the safety of the IL-12 and anti-NY-ESO-1 engineered PBL in patients receiving a non-myeloablative conditioning regimen, and to determine if patients with metastatic cancer will have clinical tumor regression following this regimen.
研究概览
简要总结
Background:
- A new cancer treatment involves collecting white blood cells from an individual, modifying them to secrete IL-2 and target the ESO-1 protein expressed on some cancers, and returning them to the body. The cells may then be able to seek out the cancer cells and destroy them. Some kinds of cancer contain a protein called ESO-1, which is found on the surface of the cells. Doctors want to modify white blood cells to have an anti-ESO-1 effect, and use them to treat the cancer that has the ESO-1. In addition to adding genes that target the ESO-1 protein to the cells, the genes for IL-12 are added to the cells. IL-12 is a protein that stimulates the immune system. This type of therapy is called gene transfer.
Objectives:
- To test the safety and effectiveness of anti-ESO-1/IL-12 white blood cells against metastatic cancer.
Eligibility:
- Individuals at least 18 years of age who have metastatic cancer that expresses ESO-1 and has not responded to standard treatments.
Design:
- Participants will be screened with a medical history and physical exam. They will also have blood tests and imaging studies.
- Participants will have leukapheresis about a month before the treatment to collect white blood cells.
- They will have chemotherapy 5 days before the treatment to suppress the immune system, and prepare the body for the anti-ESO-1/IL-12 cells.
- The anti-ESO-1/IL-12 cells will be given as an infusion.
- Participants will be monitored in the hospital during their recovery from the treatment.
- Participants will have regular followup exams every 1 to 6 months. The exams will include blood tests, imaging studies, and other studies.
Due to toxicities seen with the regimen, it was decided not to pursue the phase 2 portion of the study.
详细描述
Background:
- In prior trials we have shown that adoptive transfer of lymphocytes, transduced with a T cell receptor (TCR) that recognizes the NY-ESO-1 antigen, can mediate regression of metastatic cancer, though responses are often transient, and complete responses are rare.
- Interleukin-12 (IL-12) is an important immunostimulatory cytokine. We have constructed a retroviral vector that contains an inducible single chain IL-12 driven by an NFAT responsive promoter which can be used to mediate transfer of this gene into anti-tumor lymphocytes. This construct enables the secretion of IL-12 following stimulation of the TCR.
- Transduction of the IL-12 gene into mouse anti-tumor lymphocytes results in a profound increase in the ability of these lymphocytes to mediate tumor regression following administration to tumor bearing mice. These cells have a profound advantage in inducing anti-tumor responses because very few cells are needed and there is no requirement for the concomitant administration of interleukin-2 (IL-2) as is the case for conventional cell transfer immunotherapies.
- Based on these studies we have now used a retrovirus that encodes an inducible human single chain IL-12 driven by an NFAT responsive promoter and a retrovirus that encodes an anti-NY-ESO-1 TCR to cotransduce autologous lymphocytes for the treatment of patients with metastatic cancer that expresses the NY-ESO-1 antigen.
Objectives:
Primary objectives:
- To evaluate the safety of the administration of IL-12 and anti-NY-ESO-1 engineered lymphocytes in patients receiving a non-myeloablative conditioning regimen.
- To determine if the administration of the transduced lymphocytes to patients following a nonmyeloablative but lymphoid depleting preparative regimen will result in clinical tumor regression in patients with metastatic cancer.
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 99 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
结局指标
主要结局
To evaluate the safety of the IL-12 and anti-NY-ESO-1 engineered PBL in patients receiving a non-myeloablative conditioning regimen, and to determine if patients with metastatic cancer will have clinical tumor regression following this regimen.
时间窗: 4 years
次要结局
- To determine the in vivo survival of cotransduced gene-engineered cells.(4 years)
研究者
研究点 (2)
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