Dose Finding Study of Busulfan for Newly Diagnosed Infants with SCID

项目摘要 严重联合免疫缺陷(SCID)是一组罕见的遗传性疾病， 导致获得性免疫的严重缺陷。这种疾病可以用骨头来治疗。 如果在最初的几个月内进行骨髓或血液移植，结果会有所改善 如果有匹配的兄弟姐妹捐赠者。不幸的是，大多数人 儿童没有兄弟姐妹捐赠者，而替代捐赠者的结果 移植并不是最优的。现在越来越多的SCID在出生时就被Universal诊断出来 新生儿筛查，这将很快推广到整个50个州。决定最多的 移植治疗SCID的有效、低毒方法 确诊的新生儿需要设计良好的前瞻性多机构试验，这将 日期从未被执行过。我们已经形成了主要的免疫疾病 治疗联盟(PIDTC)是由NIAID资助的30家机构组成的小组，致力于 研究推进免疫缺陷治疗。PIDTC提议 开展一项试验，以确定治疗SCID的最佳调理方案， 假设亚清髓剂量的白花丹将导致多系 免疫重建。该试验是一项I/II期多机构剂量发现研究， 寻求招募3个剂量水平和3个供体来源(单倍体相同)各6名患者 父母、配对无关供者、脐带血献血者)，共54例SCID患者。在……里面 具体目标1我们描述了迄今为止在试验开发方面的进展，并详细说明了我们如何 将完成协议并获得监管部门的批准。在具体目标2中，我们 描述当前的PIDTC结构和我们建立临床试验基础设施的计划 为了这项研究。

Project Summary Severe combined immunodeficiency (SCID) is a group of rare genetic disorders that result in profound defects in adaptive immunity. This disorder is treatable by bone marrow or blood transplantation with improved results if performed within the first few months of age and if a matched sibling donor is available. Unfortunately the majority of children do not have a sibling donor available, and the results of alternative donor transplant are non-optimal. SCID is now increasingly diagnosed at birth by universal newborn screening, which will soon spread to the entire 50 states. Determining the most efficacious and least toxic methods to cure SCID by transplantation in these newly identified newborns requires well designed prospective multi-institutional trials, which to date have never been performed. We have formed the Primary Immune Diseases Treatment Consortium (PIDTC) an NIAID funded group of >30 institutions dedicated to studying and advancing the treatment of immunodeficiency. The PIDTC is proposing to develop a trial to determine the optimal conditioning regimen for treatment of SCID, hypothesizing that a submyeloablative dose of busulfan will result in multilineage immune reconstitution. The trial is a phase I/II multi-institutional dose finding study that seeks to enroll 6 patients on each of 3 dose levels and 3 donor sources (haploidentical parent, matched unrelated donor, cord blood donor), a total of 54 patients with SCID. In Specific Aim 1 we describe the progress to date on trial development and detail how we would complete the protocol and obtain regulatory approval. In Specific Aim 2 we describe the current PIDTC structure and our plans to build the clinical trial infrastructure for this study.