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 严重的联合免疫缺陷（SCID）是一组罕见的遗传疾病 导致自适应免疫的深刻缺陷。这种疾病可以通过骨头治疗 骨髓或血液移植具有改善的结果，如果在前几个 几个月大，如果有匹配的兄弟姐妹捐助者。不幸的是大多数 儿童没有兄弟姐妹的捐助者，还有替代捐助者的结果 移植是非最佳的。现在，SCID在出生时越来越被通用诊断 新生儿筛查将很快扩散到整个50个州。确定最多 通过移植这些新近治愈SCID的有效和最少有毒方法 确定的新生儿需要设计精良的预期多机构试验，以 日期从未执行过。我们已经形成了主要免疫疾病 治疗联盟（PIDTC）一组由30个机构组成的NIAID资助的群体 研究和提高免疫缺陷的治疗。 PIDTC建议 制定试验以确定用于治疗SCID的最佳条件方案， 假设一定余量的busulfan会导致多限制 免疫重建。该试验是I/II期多机构剂量发现研究 寻求在3个剂量水平和3个供体来源中招募6名患者（单倍型 父母，匹配的无关供体，脐带血供体），共有54例SCID患者。在 具体目标1我们描述了试验开发的进度，并详细介绍了我们如何 将完成协议并获得法规批准。在特定目标2中我们 描述当前的PIDTC结构以及我们建立临床试验基础设施的计划 对于这项研究。