High-dose MIBG With Subsequent Transplantation of Haploidentical Stem Cells in Children With Therapy Resistant Neuroblastoma
试验速览
- 阶段
- 早期 1 期
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Engraftment rate
研究概览
简要总结
Children with primary resistant or relapsed neuroblastoma who do not achieve remission with conventional chemotherapy have extremely dismal prognosis. A novel treatment strategy combining tumor targeted radioisotope treatment with metaiodobenzylguanidine (MIBG) and immunotherapeutic effect of haploidentical stem cell transplantation (haploSCT) followed by low-dose donor lymphocyte infusions will be piloted. The use of the isotope is aimed to decrease pre-transplant tumour burden. Reduced intensity conditioning containing Fludarabine, Thiotepa and Melfalan will enable sustained engraftment as well as will serve as additional anti-tumor treatment. A prompt natural killer (NK)-cell mediated tumour control may be achieved by haploidentical stem cell transplantation. The investigators hypothesize that tumour cells potentially evading NK-cell mediated immunity may be targeted by infused donor T-cells and eliminated by either MHC-dependent manner or through a bystander effect. The possible graft versus tumor effect will be evaluated in children with therapy resistant neuroblastoma.
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
- 6 Months 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Refractory neuroblastoma (any chemo/radiosensitive stable disease)
- •Relapse incl. autologous HSCT 3 m earlier
- •Primary induction failure
- •Cardiac output SF ≥25%
- •Creatinine clearance ≥40 cc/min/1.73 m2
- •Performance score of ≥50% (Lansky or Karnofsky)
- •Available haploidentical family donor, aged ≥18 yrs, HIV-neg
排除标准
- •Rapidly progressive disease
- •Pregnancy
研究组 & 干预措施
High-dose MIBG with haploidentical stem cell transplantation
High-dose MIBG followed by Fludarabine, Thiotepa and Melfalan as conditioning Before haploidentical transplantation of T-cell depleted graft
干预措施: iodine I 131 metaiodobenzylguanidine (Drug)
High-dose MIBG with haploidentical stem cell transplantation
High-dose MIBG followed by Fludarabine, Thiotepa and Melfalan as conditioning Before haploidentical transplantation of T-cell depleted graft
干预措施: Fludarabine (Drug)
High-dose MIBG with haploidentical stem cell transplantation
High-dose MIBG followed by Fludarabine, Thiotepa and Melfalan as conditioning Before haploidentical transplantation of T-cell depleted graft
干预措施: Thiotepa (Drug)
High-dose MIBG with haploidentical stem cell transplantation
High-dose MIBG followed by Fludarabine, Thiotepa and Melfalan as conditioning Before haploidentical transplantation of T-cell depleted graft
干预措施: T-cell depletion (Procedure)
High-dose MIBG with haploidentical stem cell transplantation
High-dose MIBG followed by Fludarabine, Thiotepa and Melfalan as conditioning Before haploidentical transplantation of T-cell depleted graft
干预措施: Haploidentical stem cell transplantation (Procedure)
High-dose MIBG with haploidentical stem cell transplantation
High-dose MIBG followed by Fludarabine, Thiotepa and Melfalan as conditioning Before haploidentical transplantation of T-cell depleted graft
干预措施: Donor Lymphocyte Infusion (Procedure)
High-dose MIBG with haploidentical stem cell transplantation
High-dose MIBG followed by Fludarabine, Thiotepa and Melfalan as conditioning Before haploidentical transplantation of T-cell depleted graft
干预措施: Rituximab (Drug)
High-dose MIBG with haploidentical stem cell transplantation
High-dose MIBG followed by Fludarabine, Thiotepa and Melfalan as conditioning Before haploidentical transplantation of T-cell depleted graft
干预措施: Co-transplantation of mesenchymal stem cells (Procedure)
结局指标
主要结局
Engraftment rate
时间窗: day 100
次要结局
- Immunological reconstitution(day 100)
- Incidence of acute graft versus host disease(day 100)
- Overall survival(1 year)
研究者
Jacek Toporski
MD, PhD
Lund University Hospital