A Phase I Trial for the Evaluation of the In Vivo Persistence of Adoptively-transferred Tumor-Infiltrating Lymphocytes Cultured With a Pharmacologic Inhibitor of AKT in Patients With Metastatic Melanoma
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Determine whether ACT using TIL cultured in a pharmacologic inhibitor of AktKT (during ex vivo expansion) results in enhanced in vivo persistence of TIL after adoptive transfer into autologous patients with advanced melanoma.
研究概览
简要总结
Background:
- One cancer therapy involves taking white blood cells from a person, changing them in a lab, and then giving the cells back to the person. These cells are called tumor infiltrating lymphocytes (TIL). Researchers want to grow some of the TIL cells with the drug Akti to see if they live longer than those grown without it.
Objectives:
- To see if TIL cells grown with Akti live longer than those grown without it.
Eligibility:
- Adults 18 70 with metastatic melanoma
Design:
- Participants will:
- Be screened with tests including scans, x-rays, heart and lung tests, blood and urine tests, and a <TAB>possible colonoscopy.
- Have tumor surgery or biopsy.
- Have a large catheter inserted into a vein in the upper chest.
- Receive leukapheresis for 4 5 hours. Blood is removed through a needle in an arm. White blood cells <TAB>are removed. The rest of the blood is returned by needle in the other arm.
- The cells will be changed in a laboratory.
- Participants will check into the hospital and:
- For 5 days, get 1 2 chemotherapy drugs by catheter.
- For 1 3 days, get the changed cells by catheter.
- For several days, get 2 drugs to stimulate cells, one by injection, the other by catheter.
- For 7 12 days, recover in the hospital.
- After treatment, participants will:
- Take an antibiotic and antiviral for at least 6 months.
- Return to NIH for several 2-day visits for a few years. At each visit, participants will have lab tests, imaging studies, and a physical exam. At some visits, they may have leukapheresis or blood tests.
详细描述
Background:
- Adoptive cellular immunotherapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) can mediate regression of bulky metastatic melanoma when administered with high-dose aldesleukin (IL-2) following a non-myeloablative lymphodepleting chemotherapy preparative regimen consisting of cyclophosphamide and fludarabine.
- Regression of tumor in mouse models and humans strongly correlates with anti-tumor T cells that exhibit features of immunologic memory and have a capacity to persist for long periods after adoptive-transfer into tumor-bearing hosts.
- In our preclinical work with TIL, we have identified a pharmacologic inhibitor of AKT that promotes features of immunologic memory in TIL (as evidenced by transcriptomic, proteomic, metabolomic, and functional assays described in the Background section). Consistently, AKT inhibition of human TIL significantly enhances persistence after adoptive-transfer into an immunodeficient mouse model.
- We therefore aim to evaluate whether pharmacologic inhibition of AKT in TIL may enhance persistence after adoptive-transfer into patients with advanced melanoma.
Objectives:
-
Primary objective:
-
To determine whether ACT using TIL cultured in a pharmacologic inhibitor of AKT (during ex vivo expansion) results in enhanced in vivo persistence of TIL after adoptive transfer into autologous patients with advanced melanoma.
-
Secondary 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 70 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
Patients will receive cyclophosphamide and fludarabine followed by infusion of the AKTi-treated TIL, followed by high dose aldesleukin.
干预措施: Fludarabine (Drug)
Arm 1
Patients will receive cyclophosphamide and fludarabine followed by infusion of the AKTi-treated TIL, followed by high dose aldesleukin.
干预措施: AKTi-treated TIL (Biological)
Arm 1
Patients will receive cyclophosphamide and fludarabine followed by infusion of the AKTi-treated TIL, followed by high dose aldesleukin.
干预措施: Cyclophosphamide (Drug)
Arm 1
Patients will receive cyclophosphamide and fludarabine followed by infusion of the AKTi-treated TIL, followed by high dose aldesleukin.
干预措施: Aldesleukin (Drug)
结局指标
主要结局
Determine whether ACT using TIL cultured in a pharmacologic inhibitor of AktKT (during ex vivo expansion) results in enhanced in vivo persistence of TIL after adoptive transfer into autologous patients with advanced melanoma.
时间窗: 4 years
次要结局
- Determine whether ACT using a combination of conventional and AKTi-treated TIL can mediate tumor regression by RECIST guidelines in patients with advanced melanoma(4 years)
- Determine the toxicity profile of this treatment regimen.(4 years)