Dose Finding Study of Busulfan for Newly Diagnosed Infants with SCID

白消安用于新诊断 SCID 婴儿的剂量探索研究

• 批准号: 8605312
• 负责人: SUNG-YUN PAI
• 金额: $ 25.82万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8605312
• 关键词: 2 year old; Age-Months; Allogenic; Autoimmunity; B-Lymphocytes; Birth; Blood; Blood donor; Bone Marrow; Bone Marrow Purging; Budgets; Busulfan; Canada; Case Report Form; Cessation of life; Child; Chimerism; Clinical; Clinical Protocols; Clinical Trials; Commit; Consent Forms; Cyclophosphamide; Cytotoxic agent; Data; Defect; Deficiency Diseases; Development; Diagnosis; Disease; Donor person; Dose; Early identification; Engraftment; Enrollment; Evaluation; Failure to Thrive; Funding; Hematopoietic stem cells; Hereditary Disease; Humoral Immunities; Immune; Immune System Diseases; Immune system; Immunity; Immunologic Deficiency Syndromes; Impairment; Infant; Inferior; Institution; Institutional Review Boards; Intervention Trial; Intravenous Immunoglobulins; Lead; Lymphocyte Function; Malignant - descriptor; Manuals; Methods; Monitor; Myelogenous; Myeloid Cells; National Institute of Allergy and Infectious Disease; Neonatal Screening; Newborn Infant; Newly Diagnosed; Non-Malignant; North America; Opportunistic Infections; Outcome; Parents; Patients; Phase; Procedures; Protocols documentation; Rare Diseases; Recommendation; Research Infrastructure; Running; Safety; Severe Combined Immunodeficiency; Siblings; Source; Structure; T-Lymphocyte; Toxic effect; Transplantation; Treatment Protocols; Umbilical Cord Blood; Work; adaptive immunity; chemotherapy; clinical infrastructure; clinically relevant; conditioning; data management; design; hematopoietic cell transplantation; improved; operation; prevent; prospective; protocol development; public health relevance; reconstitution; standard care

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.

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。这种疾病是可以治疗的骨 骨髓或血液移植，如果在最初的几年内进行，结果会有所改善 月龄以及是否有匹配的兄弟姐妹捐献者。不幸的是，大多数 孩子们没有兄弟姐妹捐赠者，替代捐赠者的结果 移植不是最佳的。现在，越来越多的人在出生时就被诊断出患有SCID， 新生儿筛查，这将很快蔓延到整个50个州。确定最 这些新的、有效的、毒性最小的方法通过移植治疗SCID， 确定的新生儿需要精心设计的前瞻性多机构试验， 日期从未执行过。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多个机构组成的团体，致力于 研究和推进免疫缺陷的治疗。PIDTC建议 开展一项试验，以确定治疗SCID的最佳预处理方案， 假设亚清髓性剂量的白消安将导致多谱系 免疫重建该试验是一项I/II期多机构剂量探索研究， 试图在3个剂量水平和3个供体来源（单倍相合）中的每一个上招募6名患者 父母、匹配的非亲缘供者、脐带血供者），共54例SCID患者。在 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 将完成方案并获得监管批准。具体目标2 描述当前PIDTC结构和我们建立临床试验基础设施的计划 用于本研究。