Multi-Centre Prospective Randomized Study on the Use of Two Different Doses of Rabbit Anti-Thymocyte Globulin for GVHD Prevention in Paediatric Patients With Haematological Malignancies Given an Unrelated Donor Haematopoietic Stem Cell Transplantation

Fondazione IRCCS Policlinico San Matteo di Pavia1 个研究点分布在 1 个国家目标入组 42 人开始时间: 2008年3月最近更新: 2009年7月8日

适应症

干预措施

试验速览

阶段: 3 期
发起方
入组人数: 42
试验地点: 1
主要终点: incidence and severity of acute GVHD

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

Paediatric patients affected by haematological malignancies and eligible to undergo HSCT from an unrelated volunteer will be stratified according to the degree of compatibility with their donor, the source of haematopoietic stem cells employed (BM vs. PB) and the disease phase (good vs. poor prognosis). In particular, on the basis of compatibility with their donor, patients will be allocated to 2 different arms: those transplanted from an unrelated donor either perfectly matched or with a single allelic disparity at one of the HLA loci (i.e. A, B, C, and DrB1) vs. those transplanted from an unrelated donor either with 2 allelic disparities or with an antigenic disparity at the HLA loci (i.e. A, B, C, and DrB1).

Patients enrolled in the study will be randomized to receive ATG (Fresenius) at a dosage of either 30 mg/Kg (10 mg/Kg on days -4, -3 and -2) or 15 mg/Kg (5 mg/Kg on days -4, -3 and -2).

Good prognosis patients are defined as follows: ALL in 1st CR; ALL in 2nd CR belonging to S2 group; AML in 1st CR, AML in 2nd CR and relapsed more than 6 months after stopping therapy; NHL in 2nd CR; Ph+ CML in 1st CP; refractory cytopenia.

Poor prognosis patients are defined as follows: ALL in 2nd CR belonging to the S3-S4 group; ALL in ≥ 3rd CR; AML in 2nd CR and relapsed less than 6 months after stop therapy; secondary AML; NHL in 3rd CR; Ph+ CML in 2nd CP, as well as in AP; RAEB, RAEB-t, JMML.

详细描述

Study rationale

Several reports have documented that patients given HSCT from an unrelated volunteer have:

Increased incidence and severity of acute GVHD;
Increased incidence and severity of chronic GVHD;
Increased incidence of graft rejection;
Increased risk of transplant-related death. The use of anti-thymocyte globulin (ATG) has been demonstrated to modulate alloreactivity of T-lymphocytes, reducing the risk of post-transplant immune complications, namely graft rejection and GVHD. However, concerns about the use of ATG exist, in particular referring to an increased incidence and severity of infectious complications, increased risk of malignancy recurrence and increased risk of EBV-related PTLD.

Design of the study Paediatric patients affected by haematological malignancies and eligible to undergo HSCT from an unrelated volunteer will be stratified according to the degree of compatibility with their donor, the source of haematopoietic stem cells employed (BM vs. PB) and the disease phase (good vs. poor prognosis). In particular, on the basis of compatibility with their donor, patients will be allocated to 2 different arms: those transplanted from an unrelated donor either perfectly matched or with a single allelic disparity at one of the HLA loci (i.e. A, B, C, and DrB1) vs. those transplanted from an unrelated donor either with 2 allelic disparities or with an antigenic disparity at the HLA loci (i.e. A, B, C, and DrB1).

Patients enrolled in the study will be randomized to receive ATG (Fresenius) at a dosage of either 30 mg/Kg (10 mg/Kg on days -4, -3 and -2) or 15 mg/Kg (5 mg/Kg on days -4, -3 and -2).

研究设计

研究类型: Interventional
分配方式: Randomized
主要目的: Prevention
盲法: None

入排标准

年龄范围: 1 Year 至 19 Years（Child, Adult）
性别: All
接受健康志愿者: 否

入选标准

•Unrelated donor selected using high-resolution molecular typing of HLA-A, B, C and DrB1 loci, perfectly matched or with a single allelic disparity at one of the HLA loci or with 2 allelic disparities and with an antigenic disparity at the HLA loci;
•Age comprised between 0 and 19 years;
•Life-expectancy of at least 2 months;
•Use of G-CSF mobilized PB- or BM-derived haematopoietic stem cells

排除标准

•Unrelated donor selected using high-resolution molecular typing of HLA-A, B, C and DrB1 loci, with more than one antigenic disparity or more than 2 allelic disparities at the HLA loci;
•Previous allogeneic HSCT;
•Cord blood as source of haematopoietic stem cells;
•Previous treatment with rabbit ATG in the last 3 months before HSCT;
•History of allergic reactions to rabbit ATG;
•Absence of written informed consent.