A Phase II Prospective Randomized Trial of Donor T-memory Cells (CD45RA Depleted) Infusion for Prevention of Infections After Allogeneic TcRαβ/CD19-depleted Hematopoietic Stem Cell Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 150
- 试验地点
- 2
- 主要终点
- cumulative incidence of the probability of CMV-reactivation after HSCT
研究概览
简要总结
The purpose of this prospective randomized study is to determine whether infusions of T-memory cells prevent infections in children with leukemia after allogeneic alpha, beta T-cell receptor (TcRab)/CD19-depleted hematopoietic stem cell transplantation (HSCT).
详细描述
Graft-versus-host disease (GVHD) remains the most important direct complication of hematopoietic stem cell transplantation. Methods used to prevent GVHD include diverse pharmacologic interventions and ex vivo methods of T-cell depletion, the latter being the most effective ones. Historically depletion of T-cells from the graft is associated with increased rate of graft failure, relapse of malignant disease and prolonged immune deficiency. Selective depletion of TCR-alpha/beta T-lymphocytes is a new method of hematopoietic stem cell graft manipulation, which is thought to conserve important cell populations, e.g. NK cells and gamma/delta T cells within the graft. Preliminary results suggest that TCR alpha/beta depletion ensures high engraftment rate, low early mortality and good control of GVHD. The problem of delayed immune reconstitution and life-threatening viral infections remains incompletely resolved.
Depletion of naive (CD45RA-positive) T-cells was developed as a new method of graft manipulation to prevent GVHD. Research data indicate that alloreactivity is associated mainly with naive T-cell fraction. In vitro depletion of CD45RA lowers significantly the alloreactive response while retaining reactivity to pathogens.
In previous pilot protocol the investigators confirmed that infusion after TCR-alpha/beta depleted transplantation of low doses of CD45RA-depleted mononuclear cells are safe and potentially protective against viral infections. The biologic readout for the protocol was a quantitative assessment of T-cell reactivity to common pathogens after infusion and owing to the trial results expansion of CMV-specific CD8 T-cells was discovered in most of the patients.
In current randomized protocol the investigators are posing a question if donor lymphocytes infusion (DLI) of low doses of CD45RA-depleted mononuclear cells are effective in viral prophylaxis after TCR-alpha/beta depleted transplantation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- — 至 25 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients who are considered candidates for allogeneic hematopoietic stem cell transplantation and have one of the following diagnoses:
- •Acute lymphocytic leukemia (ALL)
- •Acute myeloid leukemia
- •Acute biphenotypic leukemia
- •Acute bilinear leukemia
- •Myelodysplastic syndrome
- •Chronic myeloid leukemia
- •Transplant processing: TCR ab/CD19-depletion
- •HLA-match unrelated volunteers
- •Partly and haploidentical relative
排除标准
- •ALL patients not in remission
- •Patients with uncontrolled infections
- •Clearance of creatinine < 70 ml/min
- •Cardiac ejection fraction < 40%
- •Patients who can perform pulmonary function tests will be excluded if they have a diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) of < 50% predicted; patients who are unable to perform pulmonary function tests will be excluded if the oxygen (O2) saturation is < 92% on room air
- •Patients who have liver function test (LFTs) (including total bilirubin, aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) >= twice the upper limit of normal
- •Mental disease of both patient, patient's tutor (if patient is under age 18) and donor, that hinder understanding of main point of the study and keeping treatment plan, hygiene and sanitation
结局指标
主要结局
cumulative incidence of the probability of CMV-reactivation after HSCT
时间窗: 120 days after HSCT
cumulative incidence of acute GVHD grade II-IV.
时间窗: 150 days after HSCT
次要结局
- cumulative incidence of of CMV-disease at 100,180 and 365 days after HSCT(100, 180 and 365 days after HSCT)
- overall survival at 365 days after HSCT(365 days after HSCT)
- Event-free survival at 365 days after HSCT(365 days after HSCT)
- cumulative incidence of relapse at 6 months and 365 days after HSCT(6 months and 365 days)
- cumulative incidence of transplant-related mortality at 6 months after HSCT(6 months)
- cumulative incidence of chronic GvHD(1 year after HSCT)
- cumulative incidence of neutrophil and platelets engraftment at 14 and 30 days after HSCT(14 and 30 days)