Transfusion Medicine/Hemostasis Clinical Research

输血医学/止血临床研究

• 批准号: 6571394
• 负责人: ELLIS J NEUFELD
• 金额: $ 30万
• 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/6571394
• 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

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）： 该补助金的重点是血液系统疾病的随机临床试验，这需要NHLBI输血医学/止血临床研究网络的多中心方法。 三家哈佛教学医院组成了一个联盟，用于核心临床中心申请。 机构之间的关键联系已经到位，包括输血医学联合计划和波士顿血友病中心。 成人和儿童血液学和输血医学服务的代表，以及在我们的机构与高风险产科服务的合作。 第一项拟议的研究以儿科为重点，为期两年。 这项随机II期试验的目的是评估利妥昔单抗（抗CD 20单克隆抗体）与硫唑嘌呤在儿童和青少年重度或难治性慢性特发性血小板减少性紫癜中的疗效。 主要疗效结局为研究第90天的血小板计数。次要结局包括出血评分趋势、1年时的血小板计数、药物副作用以及在任一疗程中对“挽救”方案的需求。 我们提出的长期研究将集中在血栓性血小板减少性紫癜（TTP）的随机治疗策略。 目的是确定利妥昔单抗治疗加泼尼松和血浆置换是否有助于缓解诱导，与标准治疗的血浆置换/泼尼松单独。 主要疗效结局包括诊断后30天内接受不超过9次血浆置换术的存活患者比例（早期应答者）和24个月时存活且无复发的患者比例。 次要终点将包括死亡率、30天时缓解的患者分数、每个治疗组中至首次缓解的时间、每个患者的血浆置换程序数量、每组的复发数量以及每组中至缓解的时间和复发率，根据VWV金属蛋白酶抑制剂的存在或不存在以及VW蛋白酶活性的定量进行分层。 第三，我们提出了一个多中心联盟的III期随机研究比较两种不同的剂量方案静脉注射丙种球蛋白在妊娠期间的新生儿同种免疫性血小板减少症的风险。 建议在每个输血网络研究中建立患者血清、血浆和DNA的储存库，以促进进一步的生物学研究。