T Cell Therapy for Patients With Metastatic Renal Cell Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Number of Patients in Which the Treatment Was Tolerable
研究概览
简要总结
Adoptive T cell therapy (ACT) with tumor infiltrating lymphocytes (TIL) has achieved impressive clinical results with durable complete responses in patients with metastatic melanoma. The TILs are isolated from patients own tumor tissue followed by in vitro expansion and activation for around 4-6 weeks. Before TIL infusion the patients receive 1 week of preconditioning chemotherapy with cyclophosphamide and fludarabine. After TIL infusion Interleukin-2 is administered to support T cell activation and proliferation in vivo.
Recent studies suggest, that TIL therapy works in other cancers than Metastatic Melanoma, including Renal Cell Carcinoma. In this study TIL therapy is administered to patients with metastatic Renal Cell Carcinoma.
详细描述
Adoptive T cell therapy (ACT) with tumor infiltrating lymphocytes (TIL) has achieved impressive clinical results with durable complete responses in patients with metastatic melanoma. The TILs are isolated from patients own tumor tissue followed by in vitro expansion and activation for around 4-6 weeks. Before TIL infusion the patients receive 1 week of preconditioning chemotherapy with cyclophosphamide and fludarabine. After TIL infusion Interleukin-2 is administered to support T cell activation and proliferation in vivo.
Objectives:
To evaluate safety and feasibility when treating patients with metastatic renal cell carcinoma with ACT with TILs.
To evaluate treatment related immune responses . To evaluate clinical efficacy.
Design:
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
- •Histological proven mRCC with the possibility of surgical removal of tumor tissue of > 1 cm
- •Histology must include a clear cell component with or without a sarcomatoid dedifferentiation.
- •Metastatic disease irrespective of number of previous treatment lines. Treatment naïve pt's can be included.
- •ECOG performance status of ≤
- •IMDC prognostic group 'Favorable' or 'Intermediary'.
- •Life expectancy of > 6 months.
- •At least one measurable parameter after surgery in accordance with RECIST 1.1 -criteria's.
- •No significant toxicities or side effects (CTC ≤ 1) from previous treatments.
- •Normal ejection fraction (EF) measured by a multigated acquisition (MUGA) scan.
- •Crom EDTA clearance >40 ml/min.
- •Adequate renal, hepatic and hematological function.
- •LDH ≤ 5 times upper normal limit as a measure of tumor burden.
- •Women in the fertile age must use effective contraception. Likewise, men included in the study, as well as their partners, must use effective contraception. This applies from inclusion and until 6 months after treatment. Birth control pills, spiral, depot injection with gestagen, subdermal implantation, hormonal vaginal ring and transdermal depot patch are all considered safe contraceptives.
- •Able to comprehend the information given and willing to sign informed consent.
- •Willingness to participate in the planned controls.
排除标准
- •A history of prior malignancies, except curatively treated non-melanoma skin cancer and CIS of the cervix uteri. Patients treated for another malignancy can participate if they are without signs of disease for a minimum of 3 years after treatment.
- •Patients with cerebral metastases.
- •Patients with widespread bone or bone only metastases.
- •Severe allergies, history of anaphylaxis or known allergies to the administered drugs.
- •Severe medical conditions or psychiatric comorbidity.
- •Acute/chronic infection with HIV, hepatitis, tuberculosis among others.
- •Severe and active autoimmune disease.
- •Pregnant women and women breastfeeding.
- •Simultaneous treatment with systemic immunosuppressive drugs (including prednisolone, methotrexate among others).
- •Simultaneous treatment with other experimental drugs.
- •Simultaneous treatment with other systemic anti-cancer treatments.
- •Patients with active and uncontrollable hypercalcaemia.
研究组 & 干预措施
Patient group
All patients receive the same treatment.
Surgical removal of tumor tissue for T cell production, which takes 4-6 weeks, is performed initially.
All patients are hospitalized during treatment (one week in advance of the T cell product being ready and for approximately 3 weeks in total) and receive treatment only once.
The patients are admitted to hospital day -8 and receive lymphodepleting chemotherapy (cyclophosphamide and fludarabine on day -7 to day -1.
The TILs are infused on day 0 and Interleukin-2 therapy is administered on day 0 to day 5. Interleukin-2 is administered as high-dose i.v. bolus every eight hour starting approximately 6 hours after TIL infusion and for up to 5 days (maximum of 15 doses).
干预措施: Surgical removal of tumor tissue for T cell production (Procedure)
Patient group
All patients receive the same treatment.
Surgical removal of tumor tissue for T cell production, which takes 4-6 weeks, is performed initially.
All patients are hospitalized during treatment (one week in advance of the T cell product being ready and for approximately 3 weeks in total) and receive treatment only once.
The patients are admitted to hospital day -8 and receive lymphodepleting chemotherapy (cyclophosphamide and fludarabine on day -7 to day -1.
The TILs are infused on day 0 and Interleukin-2 therapy is administered on day 0 to day 5. Interleukin-2 is administered as high-dose i.v. bolus every eight hour starting approximately 6 hours after TIL infusion and for up to 5 days (maximum of 15 doses).
干预措施: Cyclophosphamide (Drug)
Patient group
All patients receive the same treatment.
Surgical removal of tumor tissue for T cell production, which takes 4-6 weeks, is performed initially.
All patients are hospitalized during treatment (one week in advance of the T cell product being ready and for approximately 3 weeks in total) and receive treatment only once.
The patients are admitted to hospital day -8 and receive lymphodepleting chemotherapy (cyclophosphamide and fludarabine on day -7 to day -1.
The TILs are infused on day 0 and Interleukin-2 therapy is administered on day 0 to day 5. Interleukin-2 is administered as high-dose i.v. bolus every eight hour starting approximately 6 hours after TIL infusion and for up to 5 days (maximum of 15 doses).
干预措施: Fludarabine (Drug)
Patient group
All patients receive the same treatment.
Surgical removal of tumor tissue for T cell production, which takes 4-6 weeks, is performed initially.
All patients are hospitalized during treatment (one week in advance of the T cell product being ready and for approximately 3 weeks in total) and receive treatment only once.
The patients are admitted to hospital day -8 and receive lymphodepleting chemotherapy (cyclophosphamide and fludarabine on day -7 to day -1.
The TILs are infused on day 0 and Interleukin-2 therapy is administered on day 0 to day 5. Interleukin-2 is administered as high-dose i.v. bolus every eight hour starting approximately 6 hours after TIL infusion and for up to 5 days (maximum of 15 doses).
干预措施: TIL infusion (Biological)
Patient group
All patients receive the same treatment.
Surgical removal of tumor tissue for T cell production, which takes 4-6 weeks, is performed initially.
All patients are hospitalized during treatment (one week in advance of the T cell product being ready and for approximately 3 weeks in total) and receive treatment only once.
The patients are admitted to hospital day -8 and receive lymphodepleting chemotherapy (cyclophosphamide and fludarabine on day -7 to day -1.
The TILs are infused on day 0 and Interleukin-2 therapy is administered on day 0 to day 5. Interleukin-2 is administered as high-dose i.v. bolus every eight hour starting approximately 6 hours after TIL infusion and for up to 5 days (maximum of 15 doses).
干预措施: Interleukin-2 (Drug)
结局指标
主要结局
Number of Patients in Which the Treatment Was Tolerable
时间窗: 0-24 weeks
Determine the safety of the administration of TIL therapy including lymphodepleting chemotherapy and Interleukin-2 for patients with metastatic renal cell cancer. This will be assessed clinically by whether the patients are able to receive treatment as described in the protocol.
次要结局
- Number of Infusion Products With Detectable in Vitro Anti-tumor Responses(Up to 12 months)
- Objective Response Rate(Up to 12 months)
研究者
Inge Marie Svane
MD, Professor
Herlev Hospital