Phase I Study to Assess Feasibility and Safety of Adoptive Transfer of Autologous Tumor-Infiltrating Lymphocytes in Combination with Interleukin-2 Followed by Nivolumab Rescue for Advanced Metastatic Melanoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Feasibility of TIL-ACT - successful Rapid Expansion Protocol (REP)
研究概览
简要总结
This is a single center, single arm phase I trial to test the feasibility and safety of Tumor- Infiltrating Lymphocyte-Adoptive Cell Therapy (TIL-ACT) followed by nivolumab rescue in unresectable locally advanced or metastatic melanoma patients. The trial is based on lymphodepleting chemotherapy followed by ACT, utilizing ex vivo expanded TILs in combination with high dose interleukin-2 (IL-2) (optional, depending on patient's tolerance), followed by nivolumab rescue (if indicated) for a maximum duration of 2 years.
详细描述
The objective of the trial is to define the feasibility and safety of TIL-ACT in metastatic melanoma patients. In addition, the feasibility and safety of nivolumab rescue in patients with advanced metastatic disease is examined.
Study treatment will begin with intravenous non-myeloablative (NMA) lymphodepleting chemotherapy composed by fludarabine and cyclophosphamide. Both treatments will be started on the same day. Fludarabine will be administered for five days, and cyclophosphamide for two days. TILs will be infused intravenously over a period of 20-30 minutes. Between 3 and 24 hours after the infusion of TILs, optional IL-2 will be started as a bolus administration every eight hours at minimum form the start of each administration, for a maximum of eight doses, with a maximum interval of 24 hours. In order to avoid profound and long-lasting neutropenia, pegfilgrastim will be given subcutaneously. Supportive care will be given during the recovery phase from immune depletion and IL-2 therapy.
Nivolumab rescue will be initiated for eligible patients. For all patients, the first on-treatment radiological assessment will be performed 30 days after the TIL infusion, and then at month 3, and then every 12 weeks for the first 3 years of follow-up and every 4-6 months for the next 2 years, until progression.
Two Positron Emission Tomography-Computed Tomography (PET-CT) (18FDG (Fludeoxyglucose (F18)) and 68Ga-NODAGA-RGD ((68)Ga-labelled NOTA-conjugated RGD peptide) will be performed at baseline, following chemotherapy, and between 22-30 days after the TIL infusion.
The safety assessment for TIL-ACT (TLT (treatment-limiting toxicity) period) will extend from day -7 (when NMA chemo starts) till 30 days after TIL infusion.
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 —（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
TIL-ACT +/- Nivolumab rescue
Non-myeloablative lymphodepleting chemotherapy (cyclophosphamide and fludarabine), Tumor Infiltrating Lymphocyte (TIL)-Adoptive Cell Therapy (ACT), Interleukin-2 (IL-2), Nivolumab rescue
干预措施: TIL (Other)
TIL-ACT +/- Nivolumab rescue
Non-myeloablative lymphodepleting chemotherapy (cyclophosphamide and fludarabine), Tumor Infiltrating Lymphocyte (TIL)-Adoptive Cell Therapy (ACT), Interleukin-2 (IL-2), Nivolumab rescue
干预措施: Cyclophosphamide (Drug)
TIL-ACT +/- Nivolumab rescue
Non-myeloablative lymphodepleting chemotherapy (cyclophosphamide and fludarabine), Tumor Infiltrating Lymphocyte (TIL)-Adoptive Cell Therapy (ACT), Interleukin-2 (IL-2), Nivolumab rescue
干预措施: Fludarabine (Drug)
TIL-ACT +/- Nivolumab rescue
Non-myeloablative lymphodepleting chemotherapy (cyclophosphamide and fludarabine), Tumor Infiltrating Lymphocyte (TIL)-Adoptive Cell Therapy (ACT), Interleukin-2 (IL-2), Nivolumab rescue
干预措施: Interleukin-2 (Drug)
TIL-ACT +/- Nivolumab rescue
Non-myeloablative lymphodepleting chemotherapy (cyclophosphamide and fludarabine), Tumor Infiltrating Lymphocyte (TIL)-Adoptive Cell Therapy (ACT), Interleukin-2 (IL-2), Nivolumab rescue
干预措施: Nivolumab (Drug)
结局指标
主要结局
Feasibility of TIL-ACT - successful Rapid Expansion Protocol (REP)
时间窗: Evaluated for each patient at day 0 (5-10 days after chemotherapy start). After day 0 of the last patient, the number of patients with successful REP/ start of TIL-ACT infusion will be calculated.
Number of patients for whom TIL cultures after REP achieve the required cell number and release criteria to start TIL-ACT infusion
Feasibility of TIL-ACT - successful infusion
时间窗: Evaluated for each patient at day 0 (5-10 days after chemotherapy start), up to 60 mins after start of TIL-ACT infusion. At day 0 of the last patient, the number of patients with successful TIL-ACT infusion will be calculated.
Number of patients receiving a complete TIL-ACT infusion (full NMA chemo and at least partial TIL infusion; no minimum IL-2 required)
Toxicity of TIL-ACT
时间窗: 37 days after chemotherapy start (TLT period)
Number of patients with adverse events as assessed by CTCAE version 5
次要结局
- Progression free survival (PFS) in the nivolumab rescue phase(5 years)
- Overall survival (OS)(5 years)
- Feasibility of nivolumab rescue following TIL-ACT(6 months from nivolumab start/ 100 days after end of nivolumab treatment)
- Toxicity of nivolumab rescue(6 months from nivolumab start/ 100 days after end of nivolumab treatment)
- Objective response rate (ORR)(6, 12, 24, 36, 48 and 60 months)
- Progression free survival (PFS) for TIL-ACT(5 years)
研究者
George Coukos, MD, PhD
Professor
Centre Hospitalier Universitaire Vaudois