Transplantation of Hematopoetic Stem Cells and Infusion of CD56+CD3- NK Cells From Haploidentical Donors for Patients With Hematological Malignancies
试验速览
- 阶段
- 1 期
- 入组人数
- 30
- 试验地点
- 4
- 主要终点
- To evaluate feasibility and safety of alloreactive CD56+/CD3- donor NK cells after one haplotype mismatched transplantation
研究概览
简要总结
Experimental and clinical data suggest that alloreactive NK cells can reduce the risk of graft-rejection, GvHD and leukemic relapse after HLA-mismatched transplantation. The effectiveness of allogeneic NK cells is a function of HLA-differences between donor and recipient that give rise to NK cell clones which do not express inhibitory receptors matching for the HLA molecules of the recipient. Aim of the study is to evaluate cellular therapy with alloreactive, IL-2 activated NK cells after transplantation of T-cell depleted stem cell grafts from one haplotype mismatched family donors in patients with hematological malignancies.
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 54 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with AML or ALL in first CR with the following high risk features:
- •AML with aberration Del (5q) -5, del (7q) -7, t(9;22) or t(6;9), abn 3q, 9q, 11q, 20q, 21q, 17p;
- •AML with a complex caryotype;
- •secondary AML after previous chemo- or radiotherapy or MDS;
- •Ph-positive ALL
- •Patients with AML or ALL after induction failure or in second CR
- •Patients with CML in second chronic or accelerated phase
- •Patients with malignant Lymphoma and the following high risk features:
- •relapse after autologous transplantation
- •primary chemotherapy refractory disease
- •All patients must fulfill the following criteria:
- •lack of a suitable HLA-identical family, unrelated or cord blood donor
- •no active infection, no severe impairment of cardial, pulmonary, renal and hepatic function
- •blast count in the marrow < 30%
- •informed consent
排除标准
- •active infection, no severe impairment of cardial, pulmonary, renal and hepatic function
- •blast count in the marrow > 30%
- •unable or unwilling to sign and/or understand informed consent
结局指标
主要结局
To evaluate feasibility and safety of alloreactive CD56+/CD3- donor NK cells after one haplotype mismatched transplantation
时间窗: 1 year
To evaluate feasibility and safety of cellular immunotherapy with purified alloreactive CD56+/CD3- donor NK cells after one haplotype mismatched hematopoietic stem cell transplantation in patients with high risk hematological malignancies who lack an HLA-identical donor.
次要结局
- effectiveness(2 years)
- transplant related mortality(1 year)
- technical aspects of the cell separation procedure(7 days)
- stable engraftment of haploidentical stem cell grafts can be achieved after conditioning with total body irradiation, thiotepa, fludarabine and OKT3 and subsequent transfer of megadoses of positively selected CD34+ stem cells and CD56+CD3- NK-cells.(28 days)