T Cell Therapy for Patients With Metastatic Ovarian Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Number and type of reported adverse events
研究概览
简要总结
Adoptive T cell therapy 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 acitivation and proliferation in vivo.
Recent studies suggest, that TIL therapy works in other cancers than Metastatic Melanoma, including Ovarian Cancer. In this study TIL therapy is administered to patients with metastatic Ovarian Cancer.
详细描述
Adoptive T cell therapy 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 acitivation and proliferation in vivo.
Objectives:
To evaluate safety and feasibility when treating patients with metastatic ovarian cancer 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
- Female
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed high grade serous adenokarcinoma ovarian cancer metastasis available for surgical resection (more than 1 cm3) and residual measurable disease after resection
- •Progression/reccurence of ovarian cancer after
- •line platin based chemotherapy or progression/reccurence after
- •line or additional chemotherapy
- •ECOG performance status 0-1
- •Life expectancy > 6 months
- •No significant toxicity from prior treatments, except sensoric- and motoric neuropathia and/or alopecia
- •Adequate renal, hepatic and hematological function
- •Women of childbearing potentil (WOCBP) must be using an effective method of contraception during treatment and for at least 6 months after completion of treatment
- •Able to comprehend the information given and willing to sign informed consent
排除标准
- •Other malignancies, unless followed for ≥ 5 years with no sign of disease
- •Severe allergies, history of anaphylaxis or known allergies to the administered drugs.
- •Serious medical or psychiatric comorbidity
- •Creatinine clearance < 70 ml/min
- •Acute or chronic infection with e.g. HIV, hepatitis, tuberculosis
- •Severe and active autoimmune disease
- •Pregnant and nursing women
- •Need for immunosuppressive treatment, e.g. corticosteroids or methotrexate
- •Concomitant treatment with other experimental drugs
- •Patients with uncontrolled hypercalcemia
- •Less than four weeks since prior systemic antineoplastic treatment at the time of treatment
研究组 & 干预措施
Patient group
All patients receive the same treatment. Alle patients are hospitalized during treatment (approximately 3 weeks) and receive treatment only once.
Stem Cells are harvested a minimum of 3 weeks before treatment for potential later use if the patients are having difficulties recovering from the lymphodepleting chemotherapy.
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 in an i.v. continous decrescendo regimen starting approximately 6 hours after TIL infusion with a duration of approximately 5 days.
Stem Cells can be administered after treatment if needed.
干预措施: Cyclophosphamide (Drug)
Patient group
All patients receive the same treatment. Alle patients are hospitalized during treatment (approximately 3 weeks) and receive treatment only once.
Stem Cells are harvested a minimum of 3 weeks before treatment for potential later use if the patients are having difficulties recovering from the lymphodepleting chemotherapy.
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 in an i.v. continous decrescendo regimen starting approximately 6 hours after TIL infusion with a duration of approximately 5 days.
Stem Cells can be administered after treatment if needed.
干预措施: Fludarabine (Drug)
Patient group
All patients receive the same treatment. Alle patients are hospitalized during treatment (approximately 3 weeks) and receive treatment only once.
Stem Cells are harvested a minimum of 3 weeks before treatment for potential later use if the patients are having difficulties recovering from the lymphodepleting chemotherapy.
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 in an i.v. continous decrescendo regimen starting approximately 6 hours after TIL infusion with a duration of approximately 5 days.
Stem Cells can be administered after treatment if needed.
干预措施: TIL infusion (Biological)
Patient group
All patients receive the same treatment. Alle patients are hospitalized during treatment (approximately 3 weeks) and receive treatment only once.
Stem Cells are harvested a minimum of 3 weeks before treatment for potential later use if the patients are having difficulties recovering from the lymphodepleting chemotherapy.
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 in an i.v. continous decrescendo regimen starting approximately 6 hours after TIL infusion with a duration of approximately 5 days.
Stem Cells can be administered after treatment if needed.
干预措施: Interleukin-2 (Drug)
结局指标
主要结局
Number and type of reported adverse events
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 Ovarian Cancer by reporting adverse events according to CTCAE v. 4.0.
次要结局
- Objective response rate(Up to 12 months)
- Treatment related immune responses(Up to 12 months)
- Progression free survival(Up to 12 months)
- Overall Survival(Up to 12 months)
研究者
Inge Marie Svane
M.D., Professor
Herlev Hospital