Phase I/II Study of Donor Lymphocyte Infusion With Methotrexate GVHD Prophylaxis to Hasten Immune Reconstitution After CD34+ Cell-Selected Transplant
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 38
- 试验地点
- 2
- 主要终点
- Number of Participants With Immune Recovery Following Transplantation
研究概览
简要总结
The purpose of this study is to determine the ability of a donor lymphocyte infusion (DLI) given with methotrexate to hasten immune recovery without causing severe graft-versus-host disease (GVHD) in recipients who have had a T-cell depleted transplant.
详细描述
Studies have shown that giving donor T cells after a mismatched T cell-depleted stem cell transplant can speed up recovery of T cells in the patient. This approach can cause severe graft versus host disease (GVHD). The purpose of this study is to determine whether giving a donor lymphocyte infusion (DLI) with methotrexate can accelerate immune recovery in recipients of T cell-depleted stem cell transplants. Thirty days after a T-cell depleted transplant, patients will be given a DLI. They will be monitored for immune recovery as measured by CD4 count and for GVHD toxicity.
Patients will be separated into six cohorts based on dose of DLI received: 3 x 10^4, 4 x 10^4, 5 x 10^4, 6 X 10^4, 8 x 10^4, and 10 X10^4 cells/ kg of body weight. A minimum of 3 patients will be tested at each dose starting with the lowest dose. Dose escalation will continue until the dose associated with CD4 count >100 at Day +120 after transplant without significant GVHD is determined. All patients will receive thirteen doses of methotrexate after the DLI to prevent GVHD. Patients will be followed for 2 years for outcomes.
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
- — 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have been treated on the LCH BMT 09-01 protocol
- •Signed informed consent by patient or legal guardian
排除标准
- •Active GVHD at the time when DLI are due
- •History of acute GVHD > grade I prior to DLI
- •Disease due to viral infection (eg. CMV) when DLI are due (asymptomatic viral replication or viral shedding is not a contraindication)
- •Uncontrolled bacterial or fungal infection
- •O2 saturation by pulse oximetry < 95%
- •Bilirubin > 3mg/dL or ALT > 5 x upper limit of normal
- •Creatinine > 3x baseline (at transplant)
- •ANC (WBC x % neutrophils + bands) < 500/ul
- •Significant effusions (eg. pleural or pericardial) or ascites
- •EBV-related PTLD
- •Persistent or increasing mixed chimerism requiring therapeutic DLI as defined on the LCH BMT 09-01 protocol
结局指标
主要结局
Number of Participants With Immune Recovery Following Transplantation
时间窗: 120 days after transplant
Immune recovery was measured by CD4+ cells \> 100/μL by Day 120 following transplantation
Incidence and Severity of GVHD
时间窗: 180 days after transplant
Patients were evaluated for acute GVHD due to prophylactic DLI between the day of prophylactic DLI infusion and Day +180 after transplant. GVHD was graded using standard criteria.
次要结局
- Number of Participants With Infection and EBV-related Post-transplant Lymphoproliferative Disease (PTLD)(1 year)