Nonmyeloablative Stem Cell Transplantation With CD8-depleted or Unmanipulated Peripheral Blood Stem Cells: A Prospective Randomized Phase II Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Incidence of acute GVHD in CD8-depleted versus unmanipulated groups
研究概览
简要总结
Prospective randomized study of allogeneic minitransplantation from HLA-identical family or unrelated donors comparing unmanipulated or CD8-depleted PBSC. The conditioning regimen will be 2 Gy TBI alone (related donor with low-risk of transplant rejection) or 2 Gy TBI and 3 x 30 mg/m2 fludarabine (unrelated donor or high risk of transplant rejection). Patients will receive a short but intensive immunosuppressive treatment (cyclosporine and mycophenolate mofetil) to ensure both graft-versus-host and host-versus-graft tolerance. The rationale for using PBSC instead of marrow transplant is to avoid general anesthesia of the donor and to minimize the risk of rejection. The rationale for CD8+ depletion is to diminish the risk of GVHD after PBSC transplantation or DLI.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Malignant diseases confirmed histologically and not rapidly progressing:
- •Hematologic malignancies
- •CML and other myeloproliferative disorders;
- •Multiple myeloma;
- •Non-Hodgkin's lymphoma;
- •Hodgkin's disease.
- •Non-hematologic malignancies
- •Renal cell carcinoma (metastatic).
- •Inclusion criteria
- •Male or female; female patients must use a reliable contraception method;
- •Age lower than 70 yrs (family donor) or lower than 65 yrs (unrelated donor);
- •HIV negative;
- •No terminal organ failure;
- •No uncontrolled infection, arrhythmia or hypertension;
- •Family donor (HLA-identical) or unrelated donor (matched for A-B by low resolution typing and for DRB1-DQB1 by high resolution typing);
- •No previous radiation therapy precluding the use of 2 Gy TBI
- •Informed consent given by patient or his/her guardian if of minor age.
- •Clinical situations
- •Theoretical disease indication for a standard allo-transplant, but not feasible because:
- •Age > 55 yrs;
- •Unacceptable end organ performance;
- •Patient's refusal.
- •Indication for a standard auto-transplant:
- •perform mini-allotransplantation 2-6 months after standard autotransplant.
- •Not an indication for intensification but a potential candidate for cellular immunotherapy.
- •Inclusion criteria
- •Related to the recipient (sibling, parent or child) or unrelated;
- •Male or female;
- •Weight > 15 Kg (because of leukapheresis);
- •HIV negative;
- •No major contraindication for allogeneic PBSC donation by generally accepted criteria;
- •Informed consent given by donor or his/her guardian if of minor age.
排除标准
- •Any condition not fulfilling inclusion criteria;
- •Unable to undergo leukapheresis because of poor vein access or other reasons.
研究组 & 干预措施
1
Unmanipulated PBSC
干预措施: Unmanipulated PBSC after nonmyeloablative conditioning (Procedure)
2
CD8-Depleted PBSC
干预措施: CD8-depleted PBSC after nonmyeloablative conditioning (Procedure)
结局指标
主要结局
Incidence of acute GVHD in CD8-depleted versus unmanipulated groups
时间窗: 180 days
Incidence of chronic GVHD (overall and extensive) in CD8-depleted versus unmanipulated groups.
时间窗: 1-year
次要结局
- Incidence of graft rejection [according to the risk of transplant rejection (see table 1 above)] in CD8-depleted versus unmanipulated groups.(1-year)
- T cell (CD3) and myeloid (CD13) chimerism in CD8-depleted versus unmanipulated groups.(1-year and then long term)
- Quality and timing of immune reconstitution in CD8-depleted versus unmanipulated groups.(1-year)