Phase II Study of Lymphocytes Generated With Engineered Cells for Costimulation Enhancement in Patients With Metastatic Melanoma Following Lymphodepletion
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Number of Participants With Clinical Tumor Regression.
研究概览
简要总结
Background:
- Tumor infiltrating lymphocytes (TIL) are white blood cells that have been taken from tumor tissue. The cells are modified to help them kill tumor cells, then given back to the person with cancer. By giving these cells to patients, researchers hope to improve the current treatments available for patients with melanoma that has not responded to standard therapies. The TIL will be given after treatments that will suppress the immune system. This makes it easier for the TIL to attack the cancer cells. The TIL will also be given with aldesleukin (IL-2), which is designed to help keep the TIL cells alive in the body.
Objectives:
- To study the safety and effectiveness of specially modified tumor infiltrating lymphocytes to treat melanoma that has not responded to other treatments.
Eligibility:
- Individuals at least 18 years of age who have metastatic melanoma that has not responded to other treatments.
Design:
- Participants will be screened with a physical exam and medical history. They will also have blood tests and imaging studies.
- A piece of tumor will be collected and white blood cells will be separated to make the TIL for the treatment.
- Participants will take drugs to suppress the immune system for 7 days before the start of treatment.
- Participants will receive the TIL in a single dose. Then they will receive IL-2 every 8 hours for up to 15 doses. Participants will remain in the hospital for up to 2 weeks after treatment. They will be monitored with frequent blood tests and other studies.
- After leaving the hospital, participants will have regular followup visits every 1 to 4 months for the first year. Then they will return for followup every 3 to 4 months, as directed by the study researchers.
详细描述
Background:
- Tumor Infiltrating Lymphocyte (TIL) administration and high dose interleukin (IL)-2 following lymphodepletion can mediate durable complete responses in patients with refractory melanoma. Obstacles to administration of this therapy include failure to establish TIL in vitro for about 20% of patients, long delays between tumor resection and TIL establishment resulting in poor TIL attributes for therapy and patient ineligibility due to progression, and requirements for large numbers of feeder cells for TIL expansion to therapeutic numbers.
- The K562 cell line was engineered to express the 4-1BBL costimulatory molecule and CD64 (the high affinity Fc receptor for loading with antibodies such as OKT3). The K562.CD64.4-1BBL Engineered Cells with Costimulation Enhancement (ECCE) replaced up to 75% of feeder cells in large scale TIL expansions. ECCE added to tumor cell suspensions provided costimulation in trans resulting in rapid and reliable lymphocyte growth even from tumors with no TIL growth under standard conditions.
- A cloned K562.CD64.4-1BBL-7F11 ECCE line was produced under Good Manufacturing Practice (GMP) conditions and a master cell bank has been generated. An optimized protocol was established to rapidly expand (REP) young TIL using minimum feeders and 7F11. These ECCE REPed TIL retained tumor recognition and some other attributes of standard TIL, but differed from standard TIL by containing fewer CD4+ cells and more natural killer cells.
When 7F11ECCE were added directly to single cell tumor suspensions, young TIL cultures were reliably generated even from patients who otherwise would not have a standard young TIL culture for treatment.
Objectives:
Primary objectives:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
Standard Young TIL
Tumor Infiltrating Lymphocytes : intravenous (IV) over 30 minutes on day 0
Aldesleukin : 720,000 IU/kg IV over 15 min every 8 hours (+/- 1hr) beginning within 24 hours of cell infusion and continuing for up to 5 days (max. 15 doses.)
Fludarabine : 25 mg/m2/day intravenous piggy back (IVPB) daily over 30 minutes for 5 days (days -5 to -1)
Cyclophosphamide : 60 mg/kg/day X 2 days IV over 1 hour on days -7 and -6
干预措施: Cyclophosphamide (Drug)
Standard Young TIL
Tumor Infiltrating Lymphocytes : intravenous (IV) over 30 minutes on day 0
Aldesleukin : 720,000 IU/kg IV over 15 min every 8 hours (+/- 1hr) beginning within 24 hours of cell infusion and continuing for up to 5 days (max. 15 doses.)
Fludarabine : 25 mg/m2/day intravenous piggy back (IVPB) daily over 30 minutes for 5 days (days -5 to -1)
Cyclophosphamide : 60 mg/kg/day X 2 days IV over 1 hour on days -7 and -6
干预措施: Fludarabine (Drug)
Standard Young TIL
Tumor Infiltrating Lymphocytes : intravenous (IV) over 30 minutes on day 0
Aldesleukin : 720,000 IU/kg IV over 15 min every 8 hours (+/- 1hr) beginning within 24 hours of cell infusion and continuing for up to 5 days (max. 15 doses.)
Fludarabine : 25 mg/m2/day intravenous piggy back (IVPB) daily over 30 minutes for 5 days (days -5 to -1)
Cyclophosphamide : 60 mg/kg/day X 2 days IV over 1 hour on days -7 and -6
干预措施: Aldesleukin (Biological)
Standard Young TIL
Tumor Infiltrating Lymphocytes : intravenous (IV) over 30 minutes on day 0
Aldesleukin : 720,000 IU/kg IV over 15 min every 8 hours (+/- 1hr) beginning within 24 hours of cell infusion and continuing for up to 5 days (max. 15 doses.)
Fludarabine : 25 mg/m2/day intravenous piggy back (IVPB) daily over 30 minutes for 5 days (days -5 to -1)
Cyclophosphamide : 60 mg/kg/day X 2 days IV over 1 hour on days -7 and -6
干预措施: Tumor Infiltrating Lymphocytes (Biological)
ECCE Young TIL
Tumor Infiltrating Lymphocytes : IV over 30 minutes on day 0
Aldesleukin : 720,000 IU/kg IV over 15 min every 8 hours (+/- 1hr) beginning within 24 hours of cell infusion and continuing for up to 5 days (max. 15 doses.)
Fludarabine : 25 mg/m2/day IVPB daily over 30 minutes for 5 days (days -5 to -1)
Cyclophosphamide : 60 mg/kg/day X 2 days IV over 1 hour on days -7 and -6
干预措施: Cyclophosphamide (Drug)
ECCE Young TIL
Tumor Infiltrating Lymphocytes : IV over 30 minutes on day 0
Aldesleukin : 720,000 IU/kg IV over 15 min every 8 hours (+/- 1hr) beginning within 24 hours of cell infusion and continuing for up to 5 days (max. 15 doses.)
Fludarabine : 25 mg/m2/day IVPB daily over 30 minutes for 5 days (days -5 to -1)
Cyclophosphamide : 60 mg/kg/day X 2 days IV over 1 hour on days -7 and -6
干预措施: Fludarabine (Drug)
ECCE Young TIL
Tumor Infiltrating Lymphocytes : IV over 30 minutes on day 0
Aldesleukin : 720,000 IU/kg IV over 15 min every 8 hours (+/- 1hr) beginning within 24 hours of cell infusion and continuing for up to 5 days (max. 15 doses.)
Fludarabine : 25 mg/m2/day IVPB daily over 30 minutes for 5 days (days -5 to -1)
Cyclophosphamide : 60 mg/kg/day X 2 days IV over 1 hour on days -7 and -6
干预措施: Aldesleukin (Biological)
ECCE Young TIL
Tumor Infiltrating Lymphocytes : IV over 30 minutes on day 0
Aldesleukin : 720,000 IU/kg IV over 15 min every 8 hours (+/- 1hr) beginning within 24 hours of cell infusion and continuing for up to 5 days (max. 15 doses.)
Fludarabine : 25 mg/m2/day IVPB daily over 30 minutes for 5 days (days -5 to -1)
Cyclophosphamide : 60 mg/kg/day X 2 days IV over 1 hour on days -7 and -6
干预措施: Tumor Infiltrating Lymphocytes (Biological)
结局指标
主要结局
Number of Participants With Clinical Tumor Regression.
时间窗: up to approximately 8 months
Clinical tumor regression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is a disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Progression (PD) is at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum LD.
次要结局
- Number of Participants With Serious and Non-Serious Adverse Events(Date treatment consent signed to date off study, up to approximately 8 months.)
研究者
Steven Rosenberg, M.D.
Principal Investigator
National Cancer Institute (NCI)