Pilot Prospective Clinical Study of Safety and Efficacy of Conditioning Regimen With Total Lymphoid Irradiation Before Allogeneic Hematopoietic Stem Cell Transplantation With TCRab/CD19 Graft Depletion in Severe Congenital Neutropenia
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Overall survival
研究概览
简要总结
Severe congenital neutropenia (SCN) is a group of primary immunodeficiencies caused by distinct gene mutations and characterized by neutrophil maturation impairment, which leads to neutropenia, predisposition to severe bacterial and fungal infections, and myeloid malignancies. Granulocyte-colony stimulation factor is used for pathogenetic therapy, however, no adequate response is seen in some patients.
The only curative option for SCN is hematopoietic stem cell transplantation (HSCT). An indication for HSCT in SCN is: no adequate response to G-CSF therapy, or development of malignancies, or found unfavorable mutations of SCN genes, leading to poor response to G-CSF and high risk of malignant transformation.
One of the major peculiarities of HSCT in SCN is a high risk of graft failure. That was described in few studies in SCN transplantation and was also observed in our SCN HSCT cohort. We also consider the role of TCRab/CD19 graft depletion, which is routinely used in our center for GVHD prophylaxis in increased risks of graft failure.
Another problem often observed in our patients is the relatively high risks of death of infections, developed after graft failure.
Due to predominantly early HSCT graft failure development, non-sufficient immuablation is presumed as the main reason for graft failure. Because of the low level of toxicity, associated with TCRab/CD19 depletion usage, this strategy is planned to be used in the current study. To increase an immunoablative potential of conditioning regimen in SCN, total lymphoid irradiation will be studied in combination with myeloablative agents and standardly used serotherapy.
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 Months 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical indications for HSCT in SCN: clinical diagnosis of SCN with (1) no adequate response to G-CST therapy or (2) with malignant transformation or (3) unfavorable mutations of known SCN genes
- •GATA2 deficiency
- •SCN patients age at HSCT 18 months - 21 years
- •GATA2 deficiency patients age at HSCT more than 10 years
- •Signed informed consent to participate in the study
- •Presence of HLA-matched unrelated or HLA-mismatched related donor
排除标准
- •Presence of HLA matched related donor in absence of pathologic SCN gene mutation
- •Inability to perform TCRab/CD19 graft depletion
- •Contraindications for HSCT due to patients somatic condition
结局指标
主要结局
Overall survival
时间窗: 2 years post HSCT
event free survival
时间窗: 2 years post HSCT
events - death, graft failure, secondary malignancy, relapse of malignancy
次要结局
- Incidence of early severe organ toxicity(100 days post HSCT)
- Cumulative incidence of transplant related mortality(2 years post HSCT)
- Cumulative incidence of graft failure(2 years post HSCT)
- Cumulative incidence of graft versus host disease(2 years post HSCT)
- number of patients with donor chimerism(2 years post HSCT)
- Incidence of secondary malignancies(2 years post HSCT)
- Cumulative incidence of engraftment(100 days post HSCT)
- cumulative incidence of infectious complications(1 year after HSCT)