A Prospective Randomized, Controlled Pilot Study in Order to Evaluate the Place of Thymoglobuline in Non-myeloablative Allogeneic Hemapoietic Stem-cell Transplantation (NST)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Acute GVHD occurrence
研究概览
简要总结
Allogeneic stem cell transplantation is the treatment of choice for a growing number of malignant and non-malignant indications. Until recently, myeloablative in conjunction with immunosuppressive conditioning was considered mandatory for the elimination of malignant hematopoietic cells and to prevent graft rejection. The aim of allogeneic non-myeloablative stem cell transplantation (NST) is to induce host-to-graft tolerance with fast and durable engraftment of donor stem cells, by means of conditioning, which is well-tolerated by patients. The rationale behind the NST strategy is to induce optimal graft-versus-leukemia (GVL) effects for the elimination of all malignant cells by alloreactive immunocompetent cells from a matched donor as an alternative to standard high-dose myeloablative chemo radiotherapy. The NST protocol is therefore mainly based on immunosuppression and thus contains fludarabine, low dose busulfan and anti-T-lymphocyte globulin (ATG). Thymoglobuline is a polyclonal rabbit antiserum specific for human T cells used in organ transplantation for induction of tolerance and rejection prevention and treatment. It was also used in stem-cell transplantation (SCT) for the same purposes (e.g. for generation of tolerance and rejection preclusion) as well as a treatment for graft-versus-host disease (GVHD). Data from myeloablative protocols suggest that ATG before SCT significantly reduces the risk for grade III-IV acute GVHD. This does not translate to a reduction in transplant-related mortality (TRM) because of the increased risk for infections and thus survival is unchanged. Extensive chronic GVHD was also significantly shown to be reduced in patients receiving ATG in the myeloablative setting. However, the role of ATG in the NST protocol was never evaluated in a prospective randomized trial. In view of the preliminary data suggesting of an additive effect of ATG in these circumstances we, the investigators at Hadassah Medical Organization, evaluate the effect of ATG in NST by a prospective randomized trial.
详细描述
Allogeneic stem cell transplantation (SCT) from a fully matched donor is the treatment of choice for a growing number of malignant and non-malignant indications. Until recently, myeloablative in conjunction with immunosuppressive conditioning was considered mandatory for the elimination of malignant hematopoietic cells and to prevent graft rejection. The aim of allogeneic non-myeloablative stem cell transplantation (NST) is to induce host-to-graft tolerance with fast and durable engraftment of donor stem cells, by means of conditioning, which is well-tolerated by patients. The rationale behind the NST strategy is to induce optimal graft-versus-leukemia (GVL) effects for the elimination of all malignant cells by alloreactive immunocompetent cells from a matched donor as an alternative to standard high-dose myeloablative chemo radiotherapy. The NST protocol is therefore mainly based on immunosuppression and thus contains fludarabine, low dose busulfan and anti-T-lymphocyte globulin (ATG). Thymoglobuline is a polyclonal rabbit antiserum specific for human T cells used in organ transplantation for induction of tolerance and rejection prevention and treatment. It was also used in SCT for the same purposes (e.g. for generation of tolerance and rejection preclusion) as well as a treatment for GVHD. Data from myeloablative protocols suggest that ATG before SCT significantly reduces the risk for grade III-IV acute GVHD. This does not translate to a reduction in TRM because of the increased risk for infections and thus survival is unchanged. Extensive chronic GVHD was also significantly shown to be reduced in patients receiving ATG in the myeloablative setting. However, the role of ATG in the NST protocol was never evaluated in a prospective randomized trial. In view of the preliminary data suggesting of an additive effect of ATG in these circumstances we propose the following clinical trial.
Objectives: To evaluate the effect of ATG vs. no ATG on the incidence of GVHD in patients undergoing NST.
Study parameters:
Primary end points -
- Acute GVHD occurrence.
- Acute GVHD grading.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients ages 18-75 years old with a disease necessitating allogeneic SCT.
- •Patients must have an HLA compatible donor willing and capable of donating peripheral blood stem cells preferably, or bone marrow progenitor cells using conventional techniques, and lymphocytes if indicated (HLA compatible defined as 5/6 or 6/6 matched related [A, B, DR] or 8/8 molecular [A, B, C, DR] matched unrelated donor).
- •Both patients and donor must sign written informed consents.
- •Patients must have an ECOG performance status (PS) ≤ 2; Creatinine < 2.0 mg/dl; Ejection fraction > 40%; Diffusing capacity of the lung for carbon monoxide (DLCO) > 50% of predicted; Serum bilirubin < 3 gm/dl; Elevated GPT or GOT > 3 x normal values.
排除标准
- •Not fulfilling any of the inclusion criteria
- •Active life-threatening infection
- •Overt untreated infection
- •Hypersensitivity to thymoglobuline or other rabbit produced immunoglobulin.
- •HIV seropositivity, hepatitis B or C antigen positivity with active hepatitis
- •Pregnant or lactating women.
- •Donor contraindication (HIV seropositive confirmed by Western Blot; hepatitis B antigenemia; evidence of bone marrow disease; unable to donate bone marrow or peripheral blood due to concurrent medical condition).
- •Inability to comply with study requirements.
研究组 & 干预措施
1
Thymo
干预措施: Thymoglobuline (Drug)
结局指标
主要结局
Acute GVHD occurrence
时间窗: 100d
Acute GVHD grading
时间窗: 100d
次要结局
- Time to acute GVHD(100d)
- Chronic GVHD occurrence(1y)
- Chronic GVHD grading(1y)
- Engraftment/graft rejection(21d)
- Overall survival(1y)
- Disease free survival(1y)
- Infections(1y)
- Transplant-related mortality (TRM)(1y)
- Transplant-related toxicity (TRT)(1y)