A Pilot Trial of the Combination of Vemurafenib With Adoptive Cell Therapy in Patients With Metastatic Melanoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Determine the safety of the administration of vemurafenib in conjunction with ACT consisting of autologous TIL infused along with high dose aldesleukin following a non-myeloablative lymphodepleting preparative regimen.
研究概览
简要总结
Background:
- One possible treatment for advanced melanoma involves collecting white blood cells from the person with cancer and growing them in a laboratory. The cells can then be given back to the donor. This study will use this white blood cell treatment with the cancer treatment drug vemurafenib. Vemurafenib targets melanoma cells that have a mutation in the B-raf gene, and may be able to make them shrink.
Objectives:
- To see if vemurafenib and white blood cell therapy is a safe and effective treatment for advanced melanoma.
Eligibility:
- Individuals at least 18 years and less than or equal to 66 years of age who have advanced melanoma that contains the B-raf genetic mutation.
Design:
- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected.
- White blood cells will be collected from tumor cells. These cells will be collected during surgery or a tumor biopsy.
- Participants will have leukapheresis to collect additional white blood cells for the procedure.
- Participants will take vemurafenib twice a day, starting 3 weeks before receiving the white blood cells.
- Participants will have 1 week of chemotherapy to prepare their immune system to accept the white blood cells.
- Participants will receive an infusion of their collected white blood cells. They will also receive aldesleukin for up to 5 days to boost the immune system s response to the white blood cells. They will remain in the hospital until they have recovered from the treatment.
- Participants will have frequent follow-up visits to monitor the outcome of the treatment.
详细描述
Background:
Adoptive cell therapy (ACT) with tumor infiltrating lymphocytes (TIL) can mediate the regression of bulky metastatic melanoma when administered to the autologous patient along with high-dose aldesleukin (IL-2) following a non-myeloablative lymphodepleting chemotherapy preparative regimen.
Vemurafenib (VEM) administration has been shown to mediate objective responses in 50-60 percent of patients with metastatic melanoma bearing a BRAF mutation though many of these responses are transient.
There are several reasons to suggest that the combination of ACT with VEM will synergize in the destruction of melanoma including 1) rapid tumor destruction by VEM may provide a vaccine-like stimulus to the transferred TIL; 2) VEM has been shown to upregulate the expression of melanoma antigens; 3)VEM may make residual melanoma cells more sensitive to immune damage.
Objectives:
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 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
Single Arm
Two weeks prior to the start of the preparative regimen, patients will begin taking vemurafenib. Patients will then receive lymphocyte depleting preparative regimen of cyclophosphamide and fludarabine, followed by young TIL and high dose aldesleukin
干预措施: Vemurafenib (Drug)
Single Arm
Two weeks prior to the start of the preparative regimen, patients will begin taking vemurafenib. Patients will then receive lymphocyte depleting preparative regimen of cyclophosphamide and fludarabine, followed by young TIL and high dose aldesleukin
干预措施: Young TIL (Biological)
Single Arm
Two weeks prior to the start of the preparative regimen, patients will begin taking vemurafenib. Patients will then receive lymphocyte depleting preparative regimen of cyclophosphamide and fludarabine, followed by young TIL and high dose aldesleukin
干预措施: Cyclophosphamide (Drug)
Single Arm
Two weeks prior to the start of the preparative regimen, patients will begin taking vemurafenib. Patients will then receive lymphocyte depleting preparative regimen of cyclophosphamide and fludarabine, followed by young TIL and high dose aldesleukin
干预措施: Fludarabine (Drug)
Single Arm
Two weeks prior to the start of the preparative regimen, patients will begin taking vemurafenib. Patients will then receive lymphocyte depleting preparative regimen of cyclophosphamide and fludarabine, followed by young TIL and high dose aldesleukin
干预措施: Aldesleukin (Drug)
结局指标
主要结局
Determine the safety of the administration of vemurafenib in conjunction with ACT consisting of autologous TIL infused along with high dose aldesleukin following a non-myeloablative lymphodepleting preparative regimen.
时间窗: approximately 1 year
次要结局
未报告次要终点