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（由适用提供）：儿童期间采取的支持性医疗保健措施成功地防止了严重的感染和许多其他威胁生命的镰状细胞疾病并发症（SCD），从而提高了成年的生存率。这部分是将SCD的人口统计转移到了越来越多的年轻人患有慢性健康障碍的年轻人。虽然造血细胞移植（HCT）具有治愈的潜力，但很少有SCD患者通过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）打字技术和支持性护理的进步改善了HCT的预后，特别是在无关的供体HCT之后。我们已经组织了一个跨学科的移植研究者和成人镰状细胞提供者，以及一个DAA坐标中心，在BMT临床试验网络进行临床试验中非常有经验，以测试HCT，即HCT从HLA-Mistical同胞或无关的Is safiments and Fludarabine和Fludarabine timants antiments and-Marrow and-Fludarabine ant-Fludarabine ant-Fludarabine ant-Fludarabine antiments antimantials fromant和Fludarabine antiments and-Fludarabine antiments测试。严重的SCD，为期两年的自由生存至少为80％。我们已经测试了SCD成人BMT的试点研究中，调节方案的招募和安全性的可行性。我们建议在一项临床试验中检验这一假设，即它将在接受标准支持护理的人中观察到的结果，这是对血红蛋白疾病的首次比较的结果。我们将分配60名患者15-40岁的患者，这些患者可与BMT ARM合适地匹配，并同时招募120-140 SCD，而SCD则是不可用的供体进行并行比较组的。我们建议通过以下特定目的研究患有严重镰状细胞病的成年人的HCT：1。确定HCT在患有严重镰状细胞病的年轻人中的安全性和有效性。 2。衡量供体造血对功能结果和最终器官功能的影响。我们将建立所有合格患者的长期跟进队列，目的是对HCT对结果的长期影响的未来研究。如果成功的话，拟议的比较临床试验将是第一个比较SCD的HCT和支持性护理的方法，并可以扩大患有严重SCD的成年人的治疗机会。