A Phase 2, Single-Center, Open Label Study of Autologous, Adoptive Cell Therapy Following a Reduced Intensity, Non-myeloablative, Lymphodepleting Induction Regimen in Metastatic Ovarian
试验速览
- 阶段
- 2 期
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Objective Tumor responses
研究概览
简要总结
Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) in combination with lymphodepletion and high-dose interleukin 2.
Most TIL ACT trials have been conducted as salvage therapy for patients who already had failed numerous treatments; many study participants presented with multiple metastases, frequently in visceral organs and even in the brain. The effectiveness of TIL ACT in eradicating metastatic tumors of the responding patients underlines the value of this immunotherapeutic approach.
Recent developments in the identification and selection of tumor-specific T-cell populations have facilitated the implementation of TIL ACT also in nonmelanoma malignancies. Building on the experience of Ella Lemelbaum Institute, Sheba Medical Center with ACT TIL in the treatment of metastatic melanoma, the Dept. of Oncology, Tel HaShomer has expanded the use of TIL ACT following a reduced intensity, non-myeloablative, lymphodepleting induction regimen to metastatic Melanoma, Ovarian (OC) and Cervical cancer patients. The rationale supporting these studies is to further develop the ACT TIL procedure and expand its applicability to metastatic OC and cervical cancers.
详细描述
The Sponsor is developing the ex-vivo expanded autologous Tumor Infiltrating Lymphocytes (TIL) as the Investigational Product (IP). Yet, the administration of the TIL cellular product can only be accomplished in the context of an Autologous, Adoptive Cell Therapy (ACT) procedure which is composed of the following steps:
- Reduced Intensity, non-myeloablative, lymphodepleting induction regimen using Fludarabine (25 mg/m2 for 3 days) followed by Total Body Radiation (TBR) (2 Gray as a single treatment) for 1 day
- Preparation and administration of unselected or 4-1BB enriched TIL
- Bolus high-dose (720,000 IU/kg) IL-2 will be administered to each patient every 8 hours, to tolerance. A maximum of 10 doses will be administered per patient.
- Early-stage follow-up until 30 days post-discharge
- Late-stage follow-up, such as CT scans, will be carried out four and twelve weeks after TIL administration, and then every 3 months thereafter for the first year after TIL therapy; for the second year and onwards, as clinically indicated.
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 80 Years（Adult, Older Adult）
- 性别
- Female
- 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
ACT TIL
- Reduced Intensity, non-myeloablative, lymphodepleting induction regimen using Fludarabine (25 mg/m2 for 3 days) followed by Total Body Radiation (TBR) (2 Gray as a single treatment) for 1 day
- Preparation and administration of unselected or 4-1BB enriched TIL
- Bolus high-dose (720,000 IU/kg) IL-2 will be administered to each patient every 8 hours, to tolerance. A maximum of 10 doses will be administered per patient.
干预措施: Fludarabine (Drug)
ACT TIL
- Reduced Intensity, non-myeloablative, lymphodepleting induction regimen using Fludarabine (25 mg/m2 for 3 days) followed by Total Body Radiation (TBR) (2 Gray as a single treatment) for 1 day
- Preparation and administration of unselected or 4-1BB enriched TIL
- Bolus high-dose (720,000 IU/kg) IL-2 will be administered to each patient every 8 hours, to tolerance. A maximum of 10 doses will be administered per patient.
干预措施: Radiation (Radiation)
ACT TIL
- Reduced Intensity, non-myeloablative, lymphodepleting induction regimen using Fludarabine (25 mg/m2 for 3 days) followed by Total Body Radiation (TBR) (2 Gray as a single treatment) for 1 day
- Preparation and administration of unselected or 4-1BB enriched TIL
- Bolus high-dose (720,000 IU/kg) IL-2 will be administered to each patient every 8 hours, to tolerance. A maximum of 10 doses will be administered per patient.
干预措施: TIL administration (Biological)
ACT TIL
- Reduced Intensity, non-myeloablative, lymphodepleting induction regimen using Fludarabine (25 mg/m2 for 3 days) followed by Total Body Radiation (TBR) (2 Gray as a single treatment) for 1 day
- Preparation and administration of unselected or 4-1BB enriched TIL
- Bolus high-dose (720,000 IU/kg) IL-2 will be administered to each patient every 8 hours, to tolerance. A maximum of 10 doses will be administered per patient.
干预措施: IL-2 (Drug)
结局指标
主要结局
Objective Tumor responses
时间窗: 3 years
Radiological follow up via CT to determine the sum of complete Responders (CR) + Partial Responders (PR) +Stable Disease (SD) as assessment by RECICT 1.1
Assess adverse events using NCI CTCAE V.4.03 during treatment and follow up
时间窗: 3 years
adverse events will be assess using MCI CTCAE V.4.03 during treatment and follow up
次要结局
- Overall survival (OS)(3 years)
- Progression Free Survival (PFS)(3 years)
- Response Rate( RR)(3 years)
- Quality of Life (QoL)(3 years)
研究者
Dr. Jacob Schachter MD,
Head of Ella Lemelbaum Institute for Immuno- Oncology
Sheba Medical Center