T Cell Therapy in Combination With Peginterferon for Patients With Metastatic Melanoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Number of Participants With Adverse Events/Serious 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 the 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 are administered to support T cell activation and proliferation in vivo.
In this trial the therapy is combined with peginterferon (the pegylated form of interferon alpha 2b). Interferon alpha has immunomodulatory effects and is known to upregulate HLA expression on melanoma cells and are hypothesized to synergize with TIL therapy.
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
- •Histologically confirmed unresectable stage III or stage IV metastatic melanoma Metastasis available for surgical resection (about 2 cm3) and residual measurable disease after resection
- •ECOG performance status 0-1
- •Life expectancy ≥ 3 months
- •No significant toxicity from prior treatments
- •Adequate renal, hepatic and hematologic function
- •Women of childbearing potential (WOCBP) and men in a sexual relationship with a WOCBP must be using an effective method of contraception during treatment and for at least 6 months after completion af 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, except squamous cell carcinoma or adequately treated carcinoma in situ colli uteri.
- •Cerebral metastasis. Patients with previously treated CNS metastases can participate if CNS metastases are surgically removed or treated with stereotactic radiosurgery and stable ≥ 28 days after treatment measured by MRI. Patients with asymptomatic, stable and untreated CNS metastasis can in be included according to investigators and sponsors decision.
- •Patients with ocular melanoma
- •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
A
All patients receive the same treatment.
All patients are hospitalized during treatment (approximately 3 weeks) 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 are administered on day 0 to day 5.
Interleukin-2 are administered in an i.v. continuous decrescendo regimen starting approximately 6 hours after TIL infusion with a duration of approximately 5 days
Subcutaneous injections of peginterferon alpha 2b are administered three time (day -2, day 7 and day 14)
干预措施: Cyclophosphamide (Drug)
A
All patients receive the same treatment.
All patients are hospitalized during treatment (approximately 3 weeks) 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 are administered on day 0 to day 5.
Interleukin-2 are administered in an i.v. continuous decrescendo regimen starting approximately 6 hours after TIL infusion with a duration of approximately 5 days
Subcutaneous injections of peginterferon alpha 2b are administered three time (day -2, day 7 and day 14)
干预措施: Fludarabine (Drug)
A
All patients receive the same treatment.
All patients are hospitalized during treatment (approximately 3 weeks) 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 are administered on day 0 to day 5.
Interleukin-2 are administered in an i.v. continuous decrescendo regimen starting approximately 6 hours after TIL infusion with a duration of approximately 5 days
Subcutaneous injections of peginterferon alpha 2b are administered three time (day -2, day 7 and day 14)
干预措施: TIL infusion (Biological)
A
All patients receive the same treatment.
All patients are hospitalized during treatment (approximately 3 weeks) 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 are administered on day 0 to day 5.
Interleukin-2 are administered in an i.v. continuous decrescendo regimen starting approximately 6 hours after TIL infusion with a duration of approximately 5 days
Subcutaneous injections of peginterferon alpha 2b are administered three time (day -2, day 7 and day 14)
干预措施: Interleukin-2 (Drug)
A
All patients receive the same treatment.
All patients are hospitalized during treatment (approximately 3 weeks) 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 are administered on day 0 to day 5.
Interleukin-2 are administered in an i.v. continuous decrescendo regimen starting approximately 6 hours after TIL infusion with a duration of approximately 5 days
Subcutaneous injections of peginterferon alpha 2b are administered three time (day -2, day 7 and day 14)
干预措施: Peginterferon alfa-2b (Drug)
结局指标
主要结局
Number of Participants With Adverse Events/Serious Adverse Events
时间窗: 0-24 weeks
Determine the safety of the administration of peginterferon in combination with TIL therapy including lymphodepleting chemotherapy and Interleukin-2 by reporting adverse events according to CTCAE v. 4.0
次要结局
- Overall Survival(Up to 36 months)
- Objective Response Rate(Up to 36 months)
- Progression Free Survival(Up to 36 months)
- Treatment Related Immune Responses(Up to 12 months)
研究者
Inge Marie Svane
Prof., MD
Herlev Hospital