A Phase I/II Study of IL-15 Administration Following a Non-Myeloablative Lymphocyte Depleting Chemotherapy Regimen and Autologous Lymphocyte Transfer in Metastatic Melanoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Phase 1: Maximum Tolerated Dose (MTD) of Intravenous Recombinant IL-15 as a Daily Intravenous Bolus for 10 Consecutive Days in Patients With Metastatic Melanoma Who Have Received a Lymphodepleting Chemotherapy and ACT TIL.
研究概览
简要总结
Background:
- Researchers have developed an experimental cancer treatment called cell therapy. White blood cells called lymphocytes are taken from a tumor, grown in large numbers in the lab, and then given back to the patient. Interleukin-15, given to the patient after the cells (now called Young tumor-infiltrating lymphocytes of Young TIL cells) are replaced, helps the cells to grow and boosts the immune system. This process changes your normal cells into cells that are able to recognize your tumor has been studied in the lab. These cells can destroy tumor cells in the test tube, but scientists want to see if they work inside the body.
Objectives:
-To test the effectiveness of lymphocytes drawn from tumor cells combined with interleukin-15 in treating metastatic melanoma.
Eligibility:
- Patients must be 18 - 66 years of age and have a diagnosis of metastatic melanoma.
- They will have heart and lung function tests, lab tests, and imaging procedures.
- Patients may not have conditions such as active systemic infections, blood clotting disorders, or other active major medical illnesses.
- Patients may not be pregnant or nursing.
详细描述
Background:
- Tumor Infiltrating Lymphocytes (TIL) can mediate the regression of bulky metastatic melanoma when administered to the autologous patient along with high-dose aldesleukin (IL-2) following a non-myeloablative lymphodepleting chemotherapy preparative regimen.
- In our analysis of factors that relate to the ability of this treatment to mediate objective responses, we have found a highly significant inverse correlation between reconstitution of cluster of differentiation 4 (CD4)+ forkhead box P3 (Foxp3) + T regulatory cells and the likelihood of achieving an objective response.
- Interleukin 2 (IL-2) administration has been shown to increase the number of T regulatory cells and in our trials we have found a direct relationship between the number of IL-2 doses and the reconstitution of patients at one week with CD4+ Foxp3 + T regulatory cells.
- Interleukin 15 (IL-15) is a strong T cell growth factor, but unlike IL-2, IL-15 is not involved in the generation and maintenance of CD4+ Foxp3 + T regulatory cells that can inhibit immune reactions.
- In pre-clinical adoptive cell transfer studies utilizing a murine melanoma model, the administration of IL-15 following adoptive cell transfer improved anti-tumor effects.
Objectives:
- The primary objective of this trial is to determine the safety, toxicity, and maximum tolerated dose of intravenous recombinant IL-15 administered as a daily intravenous bolus for 10 consecutive days in patients with metastatic melanoma who have received a lymphodepleting chemotherapy regimen and adoptive transfer of tumor infiltrating lymphocytes.
- An additional primary objective is to determine whether this combination is able to produce a modest number of clinical responses.
- The secondary objective involves the determination of the level of reconstitution of T regulatory cells in patients who receive cell transfer followed by IL-15 and to determine the pharmacokinetics of IL-15 levels in the serum following intravenous administration.
Eligibility:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 66 Years（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
IL-15 Following Young TIL (2 mcg)
2 mcg/kg/day x 10
干预措施: Tumor Infiltrating Lymphocytes (Biological)
IL-15 following Young TIL (0.25 mcg)
0.25 mcg/kg/day x 10
干预措施: Cyclophosphamide (Drug)
IL-15 following Young TIL (0.25 mcg)
0.25 mcg/kg/day x 10
干预措施: Fludarabine (Drug)
IL-15 following Young TIL (0.25 mcg)
0.25 mcg/kg/day x 10
干预措施: Tumor Infiltrating Lymphocytes (Biological)
IL-15 following Young TIL (0.25 mcg)
0.25 mcg/kg/day x 10
干预措施: IL-15 (Drug)
IL-15 following Young TIL (0.50 mcg)
0.50 mcg/kg/day x 10
干预措施: Cyclophosphamide (Drug)
IL-15 following Young TIL (0.50 mcg)
0.50 mcg/kg/day x 10
干预措施: Fludarabine (Drug)
IL-15 following Young TIL (0.50 mcg)
0.50 mcg/kg/day x 10
干预措施: Tumor Infiltrating Lymphocytes (Biological)
IL-15 following Young TIL (0.50 mcg)
0.50 mcg/kg/day x 10
干预措施: IL-15 (Drug)
IL-15 Following Young TIL (1 mcg)
1 mcg/kg/day x 10
干预措施: Cyclophosphamide (Drug)
IL-15 Following Young TIL (1 mcg)
1 mcg/kg/day x 10
干预措施: Fludarabine (Drug)
IL-15 Following Young TIL (1 mcg)
1 mcg/kg/day x 10
干预措施: Tumor Infiltrating Lymphocytes (Biological)
IL-15 Following Young TIL (1 mcg)
1 mcg/kg/day x 10
干预措施: IL-15 (Drug)
IL-15 Following Young TIL (2 mcg)
2 mcg/kg/day x 10
干预措施: Cyclophosphamide (Drug)
IL-15 Following Young TIL (2 mcg)
2 mcg/kg/day x 10
干预措施: Fludarabine (Drug)
IL-15 Following Young TIL (2 mcg)
2 mcg/kg/day x 10
干预措施: IL-15 (Drug)
结局指标
主要结局
Phase 1: Maximum Tolerated Dose (MTD) of Intravenous Recombinant IL-15 as a Daily Intravenous Bolus for 10 Consecutive Days in Patients With Metastatic Melanoma Who Have Received a Lymphodepleting Chemotherapy and ACT TIL.
时间窗: 2 years
Intravenous recombinant IL-15 as a daily intravenous bolus for 10 consecutive days in patients with metastatic melanoma who have received a lymphodepleting chemotherapy and ACT TIL with dose escalation (i.e., dose level 1: 0.25 mcg, dose level 2: 0.50 mcg, dose level 3: 1 mcg, and dose level 4: 2 mcg) to further characterize the safety of the MTD prior to starting the phase 2 portion.
Number of Participants With Adverse Events
时间窗: 8 months, 9 days
Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
次要结局
未报告次要终点
研究者
Steven Rosenberg, M.D.
Principal investigator
National Institutes of Health Clinical Center (CC)