Intraperitoneal Infusion of ex Vivo-cultured Allogeneic NK Cells in Recurrent Ovarian Carcinoma Patients (a Phase I Study)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Incidence of treatment emergent adverse events
研究概览
简要总结
This study investigates an innovative treatment for recurrent ovarian cancer exploiting ex vivo-generated allogeneic natural killer (NK) cells with or without preceding non-myeloablative conditioning chemotherapy.
详细描述
This study investigates an innovative treatment for recurrent ovarian cancer exploiting ex vivo-generated allogeneic natural killer (NK) cells with or without preceding non-myeloablative conditioning chemotherapy.
This study is a phase I safety and feasibility study in a series of 12 patients who are suffering from recurrent ovarian, fallopian tube or primary peritoneal cancer. Prior to NK cell infusion, a laparoscopy is performed to place a catheter in the peritoneal cavity. The first cohort of three patients will receive an intraperitoneal infusion of allogeneic UCB-NK cells generated ex vivo from CD34+ hematopoietic progenitor cells obtained from an allogeneic UCB unit without a preparative regimen. In the second group of three patients the same UCB-NK cell dosage will be given with a preparative regimen of four days non-myeloablative immunosuppressive conditioning regimen with cyclophosphamide and fludarabine (CyFlu). If no severe toxicity is seen in these 6 patients, an extension cohort of 6 patients will be included to answer the secondary objective.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients suffering from their second recurrence of ovarian, fallopian tube or primary peritoneal cancer, with an elevated serum level of CA-125 on two successive time points with 28 days in between, reaching a value of more than 2 times nadir and above 35 U/ml without gastrointestinal symptoms.
- •Able to undergo laparoscopic IP port placement and IP treatment administration
- •Adequate organ function
- •Age 18 years or older
- •Age under 76 years.
- •Karnofsky performance status >70% (see appendix 2)
- •Life expectancy > 6 months
- •At least 28 days after last anti cancer treatment, before start of preparative regimen
- •Written informed consent
- •Availability of a partially HLA-matched UCB unit
排除标准
- •Patients on immunosuppressive drugs
- •Patients with active infections (viral, bacterial or fungal) that requires specific therapy. Acute anti-infectious therapy must have been completed within 14 days prior to study treatment
- •Laparoscopic adhesion score >4 out of
- •Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or symptomatic ischemic heart disease (appendix 4)
- •Severe pulmonary dysfunction (CTCAE III-IV) (appendix 4)
- •Severe renal dysfunction (MDRD<50) (appendix 4)
- •Severe hepatic dysfunction (serum bilirubin or transaminases > 3 times normal level) (appendix 4)
- •Severe neurological or psychiatric disease
研究组 & 干预措施
NK-cells without preparative regimen
NK-cells without preparative regimen
干预措施: UCB-NK cells (Biological)
NK-cells with preparative regimen
NK-cells with preparative regimen
干预措施: UCB-NK cells (Biological)
NK-cells with preparative regimen
NK-cells with preparative regimen
干预措施: Chemotherapy (Drug)
结局指标
主要结局
Incidence of treatment emergent adverse events
时间窗: 6 months
Incidence of treatment emergent adverse events (following CTCAE criteria)
次要结局
- in vivo expansion of the infused UCB-NK cells(28 days)
- in vivo lifespan of the infused UCB-NK cells(28 days)
- Measurement of in vitro cytolytic activity of infused NK cells(28 days)
- the effect of NK cell infusion on measurable disease(6 months)