Hematopoietic Stem Cell Transplantation for Young Adults with SCD - DCC

年轻 SCD 患者的造血干细胞移植 - DCC

• 批准号: 9127357
• 负责人: MARY EAPEN
• 金额: $ 29.43万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9127357
• 关键词: Address; Adherence; Adolescent and Young Adult; Adult; Affect; African American; Age; Blood; Busulfan; Child; Childhood; Chronic; Clinical; Clinical Trials; Clinical Trials Cooperative Group; Clinical Trials Network; Collaborations; Collection; Complement; Complex; Conduct Clinical Trials; Dana-Farber Cancer Institute; Data Analyses; Data Coordinating Center; Data Quality; Data Reporting; Databases; Development; Disease; Disease-Free Survival; Eastern Cooperative Oncology Group; Enrollment; Ensure; Funding; Future; Goals; HLA Antigens; Health; Healthcare; Hematology; Hematopoiesis; Hematopoietic Stem Cell Transplantation; Hemoglobin; Human Resources; Impairment; Individual; Infection; Information Dissemination; Institutes; Knowledge; Lead; Learning; Life; Longevity; Longitudinal Studies; Maintenance; Marrow; Measures; Medical; Morbidity - disease rate; National Cancer Institute; National Heart, Lung, and Blood Institute; Organ; Outcome; Patients; Pilot Projects; Play; Population; Protocols documentation; Provider; Regimen; Research; Research Infrastructure; Research Personnel; Role; Safety; Seasons; Siblings; Sickle Cell; Sickle Cell Anemia; Supportive care; System; Techniques; Testing; Therapeutic; Toxic effect; Transplantation; United States; Wisconsin; arm; cohort; comparative; conditioning; data management; demographics; design; experience; fludarabine; follow-up; functional outcomes; hematopoietic cell transplantation; human leukocyte antigen testing; improved; improved outcome; international center; medical schools; meetings; member; phase II trial; pilot trial; prevent; safety study; statistical center; thymocyte; young adult

 DESCRIPTION (provided by applicant): Supportive health care measures instituted during childhood successfully prevent serious infections and many other life-threatening complications of sickle cell disease (SCD), resulting in improved survival to adulthood. This has, in part, shifted the demographics of SCD to include a growing proportion of young adults with chronic health impairments. While hematopoietic cell transplantation (HCT) has curative potential, very few individuals with SCD are treated by HCT, due in part to the toxicity of this treatment. Recently, advances in Human Leukocyte Antigen (HLA) typing techniques and supportive care have improved outcomes of HCT, particularly after unrelated donor HCT. We have organized an interdisciplinary group of transplant investigators and adult sickle cell providers as well as a daa coordinating center very experienced in the conduct of clinical trials for the BMT clinical trials network to test the hypothesis that HCT from an HLA-identical sibling or unrelated marrow donor with a conditioning regimen of Busulfan, Fludarabine and anti-thymocyte is safe and effective in young adults with severe SCD with a two year event free survival of at least 80%. We have tested the feasibility of recruitment and safety of the conditioning regimen in a pilot study of BMT in adults with SCD. We propose to test this hypothesis in a clinical trial that it wil compare outcomes after HCT to outcomes observed in those who receive standard supportive care, the first comparison of this kind in hemoglobin disorders. We will assign 60 patients age 15-40 years who have an available suitably matched donor to the BMT arm and will contemporaneously enroll 120-140 SCD who do not an available suitable donor to a parallel comparison cohort. We propose to investigate HCT in adults with severe sickle cell disease by the following specific aims: 1. Determine the safety and efficacy of HCT in young adults with severe sickle cell disease. 2. Measure the impact of donor hematopoiesis on functional outcomes and end-organ function. We will establish a long term follow up cohort of all eligible patients for the purpose of future studies of long term impact of HCT on outcome sin SCD. If successful, the proposed comparative clinical trial would be the first to compare HCT and supportive care for SCD, and could broaden the therapeutic opportunities for adults with severe SCD.

 描述（由申请人提供）：儿童时期制定的支持性医疗保健措施成功地预防了镰状细胞病（SCD）的严重感染和许多其他危及生命的并发症，从而提高了成年期的生存率，这在一定程度上改变了儿童的人口结构。 SCD 包括越来越多患有慢性健康障碍的年轻人 虽然造血细胞移植 (HCT) 具有治愈潜力，但很少有 SCD 患者接受 HCT 治疗，部分原因是这种治疗的毒性。最近，人类白细胞抗原 (HLA) 分型技术和支持护理的进步改善了 HCT 的结果，特别是在无关捐赠者 HCT 后，我们组织了一个由移植研究人员和成人镰状细胞提供者组成的跨学科小组以及一个经验丰富的 daa 协调中心。为 BMT 临床试验网络进行临床试验，以检验以下假设：HCT 来自 HLA 相同的兄弟姐妹或无关的骨髓捐赠者，采用白消安、氟达拉滨和抗胸腺细胞预处理方案对于患有严重 SCD 的年轻人来说是安全有效的，两年无事件生存率至少为 80%。我们已经在 SCD 成人的 BMT 试点研究中测试了预处理方案的可行性和安全性。在一项临床试验中检验这一假设，该试验将比较 HCT 后的结果与接受标准支持治疗的患者观察到的结果，这是血红蛋白疾病方面的首次比较。我们将分配 60 名年龄在 15-40 岁之间且具有适当支持治疗的患者。匹配的捐赠者到 BMT 组，同时将招募 120-140 名没有合适捐献者的 SCD 进行平行比较队列。我们建议通过以下具体目标来研究患有严重镰状细胞病的成人的 HCT： 1. 确定安全性和有效性。 2. 测量供体造血对功能结果和终末器官功能的影响，目的是对所有符合条件的患者建立长期随访队列。 HCT 对 SCD 结局的长期影响的未来研究如果成功，拟议的比较临床试验将是第一个比较 HCT 和 SCD 的支持治疗的研究，并且可以扩大患有严重 SCD 的成人的治疗机会。