Transfusion Medicine/Hemostasis Clinical Research

输血医学/止血临床研究

• 批准号: 6931550
• 负责人: ELLIS J NEUFELD
• 金额: $ 45万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6931550
• 关键词: adolescence (12-20); antineoplastics; azathioprine; blood disorder chemotherapy; blood transfusion; child (0-11); clinical research; cooperative study; embryo /fetus therapy; hemostasis; histocompatibility; human pregnant subject; human subject; human therapy evaluation; immunoglobulins; immunotherapy; monoclonal antibody; patient oriented research; plasmapheresis; prednisone; thrombocytopenia; thrombocytopenic purpura; thrombosis; von Willebrand factor; adolescence (12-20); antineoplastics; azathioprine; blood disorder chemotherapy; blood transfusion; child (0-11); clinical research; cooperative study; embryo /fetus therapy; hemostasis; histocompatibility; human pregnant subject; human subject; human therapy evaluation; immunoglobulins; immunotherapy; monoclonal antibody; patient oriented research; plasmapheresis; prednisone; thrombocytopenia; thrombocytopenic purpura; thrombosis; von Willebrand factor

DESCRIPTION (provided by applicant): The focus of this grant is randomized clinical trials for hematologic disorders, which require a multi-center approach in the NHLBI Transfusion Medicine/Hemostasis Clinical Research Network. Three Harvard teaching hospitals form a consortium for this Core Clinical Center application. Key linkages among the institutions are in place, including the Joint Program in Transfusion Medicine, and the Boston Hemophilia Center. Adult and pediatric hematology and transfusion medicine services are represented, as well as collaboration with the high-risk obstetrics services at our institutions. The first proposed study has a pediatric focus and two-year time frame. The aim of this randomized phase II trial is to assess the efficacy of rituximab (anti-CD20 monoclonal antibody) vs. azathioprine, in children and adolescents with severe or refractor chronic idiopathic thrombocytopenic purpura. The primary efficacy outcome will be platelet counts at study day 90. Secondary outcomes include bleeding score trend, platelet counts at one year, side effects of medication, and requirement for 'salvage' regimens during either course of therapy. Our proposed long-term study will focus on randomized treatment strategies in thrombotic thrombocytopenic purpura (TTP). The aim is to determine whether rituximab therapy in addition to prednisone and plasmapheresis will facilitate remission induction, compared to standard therapy of plasmapheresis/ prednisone alone. Primary efficacy outcomes include the fraction of patients alive with no more than 9 plasma exchange procedures at 30 days from diagnosis (early responders) and the fraction of patients alive and relapse-free at 24 months. Secondary endpoints will include the death rate, the fraction of patients in remission at 30 days, the time to first remission in each treatment group, the number of plasma exchange procedures per patients, the number of relapses per group, and the time to remission and relapse rate, in each group, stratified for the presence of absence of VWV metalloprotease inhibitors and quantification of VW protease activity. Third, we propose a multicenter consortium for a phase III randomized study comparing two different dosage regimens of intravenous gamma globulin during pregnancies at risk for neonatal alloimmune thrombocytopenia. A repository for sera, plasma, and DNA from patients in each of the transfusion network studies is proposed, to facilitate further biological studies.

描述（由申请人提供）： 该赠款的重点是血液学疾病的随机临床试验，该试验需要在NHLBI输血医学/止血临床研究网络中采用多中心方法。 三家哈佛教学医院构成了该核心临床中心应用程序的财团。 机构之间的关键联系已到位，包括输血医学联合计划和波士顿血友病中心。 代表了成人和小儿血液学和输血医学服务，以及与我们机构的高风险妇产科服务的合作。 首次提出的研究具有小儿重点和两年的时间范围。 这项随机II期试验的目的是评估利妥昔单抗（抗CD20单克隆抗体）与硫唑嘌呤，对患有严重或抑制剂慢性特发性血小板性血小板性血小板性紫红色的儿童和青少年的疗效。 主要功效结果将是在研究第90天的血小板计数。次要结果包括出血得分趋势，一年的血小板计数，药物副作用以及对任何治疗过程中“挽救”方案的要求。 我们提出的长期研究将重点介绍血栓性血小板减少紫癜（TTP）的随机治疗策略。 目的是确定与单独的血浆置换/泼尼松的标准治疗相比，与泼尼松和血浆外发生外，利妥昔单抗治疗是否会促进缓解诱导。 一级疗效结果包括在诊断后30天（早期响应者）30天的活着的患者比例不超过9个血浆交换程序，以及24个月时活着的患者和无复发的患者的比例。 次要终点将包括死亡率，30天的缓解患者的比例，每个治疗组首次缓解的时间，每个患者的血浆交换程序的数量，每组复发的数量以及缓解和复发率的时间，每组的时间分层，以缺乏VWV金属蛋白酶抑制剂的缺乏VW蛋白质的量化和VW蛋白质的量化活动。 第三，我们提出了一个多中心财团，用于一项III期随机研究，比较怀孕期间两种不同的静脉伽马球蛋白剂量方案，面临新生儿同种免疫性血小板减少症的风险。 提出了每个输血网络研究中患者的血清，血浆和DNA的存储库，以促进进一步的生物学研究。