The Use of Granulocyte Transfusions After Umbilical Cord Blood Transplant for Leukaemia: A Prospective, Non-randomised, Single-centre Study to Evaluate Safety and Immune Reconstitution
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- What is the number of patients with grade 1-4 cytokine release syndrome, related to the granulocytes infusions?
研究概览
简要总结
Although most children with leukaemia are cured using drugs (chemotherapy) alone, for some children additional treatments are needed. Stem cell transplant can cure children where chemotherapy and other drugs have failed. In this case, the immune cells of the donor attack the leukaemia cells of the patient. Cord blood collected from the placenta of unrelated babies is often used as a donor cell source and appears to work well at controlling leukaemia and less likely to cause complications such as when the immune cells also mistakenly attack healthy tissues (called graft versus host disease, GVHD).
The investigators have noticed that during cord blood transplant, the donor immune system appears to recover more quickly and not be associated with GVHD, when a type of blood transfusion containing white cells are also given to the patient. The infused white cells appear to stimulate the donor immune cells to expand much more than usually seen.
During this research, the investigators will study this immune cell expansion during cord blood transplant in children with difficult-to-cure leukaemia who also receive a transfusion of white cells, termed granulocytes. The investigators will assess the safety of the effects of the white cell transfusions and the immune cell expansion on the child, and look at the outcomes on the patient's leukaemia, and whether there is GVHD or not.
详细描述
Most children with acute leukaemia are cured with chemotherapy alone but a few children are either refractory to such therapy, or relapse after it has been administered.
Some of these relapsed or refractory children are given HCT (hematopoietic cell transplantation), and some will be cured with HCT. HCT acts to cure children with leukaemia in two ways:
- There is chemotherapy given before the transplant, to get rid of recipient marrow and the recipient immune system. This chemotherapy is of higher dose than is given in standard chemotherapy protocols, and this dose escalation might overcome the resistance to chemotherapy that is inherent in children with relapsed or refractory disease.
- The engrafting immune system - derived from the HCT donor - recognises the residual leukaemia and rejects it. This is known as graft-versus-leukaemia, and this Is the main way that transplant cures refractory diseases.
Most children with refractory and / or relapsed leukaemia will die of their leukaemia. Transplant offers a chance of cure where conventional therapies will fail. Transplant works through this graft-versus leukaemia effect. This is related to graft-versus-disease (GVHD) and involves a recognition by donor derived T-cells of differences in the host leukaemia cells, and more generally in the recipient.
In general, the risk of relapse after transplant is:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- — 至 16 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children, aged <16 years, undergoing a first allogeneic, unrelated donor, T-cell replete, umbilical cord blood HSCT for high risk acute leukaemia.
- •Availability of at least a 6/8 allelic matched cord blood, of adequate cell dose, after allele-level matching at HLA (Human Leukocyte Antigen)-A, -B, -C, and -DRB1
- •Informed consent by parent or guardian. Age appropriate Assent will also be collected in those Children age 16 and under.
排除标准
- •Patients participating in other HSCT clinical trial
- •The transplant not indicated according to National Health Service England (NHSE) and British Society of Bone Marrow Transplant (BSBMT) Paediatric Transplant Group.
- •Pooled Granulocyte Transfusion contraindicated for any reason
- •Previous T cell replete unrelated donor cord blood transplant
- •Patients with a previous history of sensitivity to granulocyte transfusion will be excluded from the study
研究组 & 干预措施
Granulocytes
Patient to receive pooled granulocytes for 7 days concurrently. 20 participants will be approached for this arm.
干预措施: Granulocytes (Biological)
Control
Non-randomised control arm, where patients who are receiving a stem cell transplant, as described in the eligibility criteria, are asked for a blood sample. This is to establish a baseline versus the experimental arm. 20 participants will be approached for this arm.
结局指标
主要结局
What is the number of patients with grade 1-4 cytokine release syndrome, related to the granulocytes infusions?
时间窗: 2 years
This is to access safety of the granulocyte infusions.
What is the number of patients with allo-immunisation after the granulocyte infusions?
时间窗: 2 years
This is to access safety of the granulocyte infusions.
次要结局
- What is the median disease-free and overall survival in this patient cohort?(2 years)
- How many patients enter flow and molecular remission after the transplant?(2 years)
- What is the median day to neutrophil and to platelet engraftment, and compared with a control group of cord blood transplant recipients not receiving granulocytes?(2 years)
- How many patients experience grade II-IV GvHD?(2 years)
- What is the median date of cessation of immune suppression after the transplant, and compared with a control group of cord blood transplant recipients not receiving granulocytes?(2 years)