Pilot Study of Immunotherapy With ex Vivo Expanded Haploidentical Natural Killer Cells for Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Incidence of Treatment-Emergent Adverse Events
研究概览
简要总结
The purpose of this study is to estimate the safety of ex vivo expanded haploidentical natural killer (NK) cells for patients with leukemia.
详细描述
Immunotherapy with natural killer (NK) cells may improve the results of treatment for patients with cancer. However, for better efficiency high doses of NK cells are required. For this purpose, NK cells were expanded in the presence of feeder K562 cells gene-modified for expression 4-1BBL and membrane bound IL-21. In the result of expansion, large number of activated NK cells are obtained.
Protocol of immunotherapy includes conditioning (fludarabine + cyclophosphamide or any other protocol of chemotherapy) followed by expanded NK cells intravenous infusion. To sustain proliferation of donor NK cells in vivo patients receive 6 doses of Il-2 every second day. 10 patients will be enrolled in phase I to test different doses of NK cells: 20, 50, 70, 100 and >100 x 10^6/kg.
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
- 1 Year 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Relapsed acute myeloid or lymphoblastic leukemia
- •Primary refractory myeloid or lymphoblastic leukemia
- •Karnofsky or Lansky performance scale greater or equal to 70
- •Written informed consent
- •Haploidentical family donor
- •> 18 years old
- •Donor suitable for cell donation and apheresis according to standard criteria
- •Written informed consent
排除标准
- •Uncontrolled infection
- •Severe hepatic dysfunction: SGOT or SCPT >=5x upper limit of normal for age
- •Positive serology for human immunodeficiency virus (HIV)
- •Pregnancy or breast feeding
- •Positive serology for HIV, hepatitis B or C.
研究组 & 干预措施
NK cells + IL-2
After cycle of chemotherapy patient receive one intravenous infusion of expanded haploidentical NK cells on day 0. On alternate days, 6 doses of subcutaneous IL-2 is administered with start on day -1.
干预措施: Expanded Haploidentical Natural Killer cells (Biological)
NK cells + IL-2
After cycle of chemotherapy patient receive one intravenous infusion of expanded haploidentical NK cells on day 0. On alternate days, 6 doses of subcutaneous IL-2 is administered with start on day -1.
干预措施: IL-2 (Drug)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events
时间窗: 1 months
Adverse events will be graded according to the CTCAE v4.0
次要结局
- Median time to leukocytes and platelets recovery(2 months post infusion)
- Days of persistence of adoptively-transferred haploidentical NK cells(1 months)
- Occurrence of disease response(1 months post infusion)
- Number of T, B, NK, activated T and NK cells after immunotherapy(1 months post infusion)