1/2A Phase III Randomized Trial Comparing Unrelated Donor Bone Marrow Transplantation with Immune Suppressive Therapy for Newly Diagnosed Pediatric and Young Adult Patients with Severe Aplastic Anemia

1/2A III 期随机试验，比较无关供体骨髓移植与免疫抑制治疗对新诊断患有严重再生障碍性贫血的儿童和年轻成人患者的影响

• 批准号: 10370775
• 负责人: Bronwen Shaw
• 金额: $ 116.17万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2029-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10370775
• 关键词: Address; Adherence; Age; American; Aplastic Anemia; Area; Biological Factors; Biology; Biometry; Blood; Bone Marrow Transplantation; Bone marrow failure; Boston; Canada; Cell Therapy; Child; Child Care; Childhood; Clinical; Clinical Trials; Clinical Trials Network; Collaborations; Communication; Complement; Cyclosporine; Data; Data Collection; Data Coordinating Center; Development; Disease; Enrollment; Ensure; Equipoise; Fertility; Funding; Goals; Hematology; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; Human Resources; Immune; Immunosuppression; Incidence; Infrastructure; Knowledge; Lead; Leadership; Marrow; Medidata; Monitor; National Heart, Lung, and Blood Institute; Newly Diagnosed; North America; Outcome; Participant; Patient Outcomes Assessments; Patients; Pediatric Hospitals; Phase; Pilot Projects; Quality of life; Randomized; Randomized Controlled Trials; Reporting; Research; Research Personnel; Resources; Risk; Role; Running; Seasons; Siblings; Survival Rate; System; Time; Transplantation; Wisconsin; arm; autoimmune pathogenesis; base; clinical application; clinical investigation; clinical research site; design; electronic data; experience; improved; international center; medical schools; member; pilot trial; programs; prospective; randomized trial; recruit; research study; response; safety and feasibility; transplantation therapy; trial comparing; young adult

ABSTRACT Acquired severe aplastic anemia (SAA) is a rare bone marrow failure disorder with an annual incidence of 3-4 per million in North America (300-500 cases < age 25 in the US yearly). The large majority of cases are caused by autoimmune destruction of hematopoietic stem cells (HSCs); accordingly the disease can be treated and often cured by either immune suppression therapy (IST) or bone marrow transplantation (BMT). The ATG/ cyclosporine (CsA) combination developed in the 1990s is the preferred IST approach for newly diagnosed SAA patients and has response rates of 60-80%, with 5-year survival exceeding 90%. BMT from an HLA matched sibling donor (MSD) is the standard for initial therapy for younger, newly diagnosed patients with long-term survival rates of over 95% however, only 20% of patients have a suitable sibling donor, consequently, the large majority of patients receive IST for initial therapy. Outcomes of matched unrelated donor (MUD) BMT for SAA have improved significantly over the past decade, with studies reporting similar outcomes for BMT using MUD compared to MSD. Although these data are provocative, MUD BMT carries significant risks, and a state of equipoise exists between the two approaches. To address this challenge, the North American Pediatric Aplastic Anemia Consortium (NAPAAC), in collaboration with the Pediatric Transplantation and Cellular Therapy Consortium (PTCTC) conducted an NHLBI funded pilot trial, which has shown the feasibility and safety of randomizing patients between IST and MUD BMT. In this cluster application, the Resource for Clinical Investigation in BMT (RCI BMT), the prospective clinical trial arm of the Center for International Blood and Marrow Transplant Research (CIBMTR), will serve as the Data Coordinating Center (DCC) to manage the definitive Phase III Randomized Controlled Trial (RCT) in collaboration with the Clinical Coordinating Center (CCC) partnership of NAPAAC and PTCTC. Our specific aims are to: 1) compare the proportion of SAA patients with immune suppression free survival with adequate counts at two years for patients randomized to IST versus BMT, including to understand the impact of either therapy on fertility, quality of life and biological factors, 2) support and manage the efficient implementation, governance and completion of this RCT, and 3) leverage existing systems and expertise to ensure adherence to high quality data collection. The proposed DCC provides an efficient and experienced infrastructure that leverages existing relationships and a framework which has successfully delivered clinical trials over 15 years, including a seasoned statistical team. These assets will ensure that this trial is designed, analyzed and conducted with the utmost integrity and efficiency and that it will meet its goal of advancing knowledge regarding the best therapy for children and young adults with SAA.

抽象的 获得的严重性性贫血（SAA）是一种罕见的骨髓衰竭障碍，年龄为3-4 北美每百万（300-500案件<美国年龄25岁）。绝大多数案件是 由造血干细胞的自身免疫性破坏（HSC）引起；因此，该疾病可能是 通过免疫抑制疗法（IST）或骨髓移植（BMT）治疗并经常治愈。 1990年代开发的ATG/环孢菌素（CSA）组合是新的IST方法 诊断为SAA患者，应答率为60-80％，5年生存率超过90％。来自An的BMT HLA匹配的兄弟姐妹供体（MSD）是针对新诊断的患者的初始治疗的标准 然而，长期存活率超过95％，只有20％的患者有合适的兄弟姐妹供体， 因此，绝大多数患者接受初始治疗的IST。匹配无关的结果 在过去的十年中 与MSD相比，使用泥浆的BMT结果。尽管这些数据具有挑衅性，但Mud BMT携带 两种方法之间存在重大风险和一种平衡状态。为了应对这一挑战， 与儿科合作 移植和细胞治疗联盟（PTCTC）进行了NHLBI资助的试验试验，该试验已有 显示了IST和MUD BMT之间随机化患者的可行性和安全性。在这个集群中 应用，BMT（RCI BMT）的临床研究资源， 国际血液和骨髓移植研究中心（CIBMTR）将作为数据 协调中心（DCC）管理确定的III期随机对照试验（RCT） 与NAPAAC和PTCTC的临床协调中心（CCC）合作伙伴关系的合作。我们的具体 目的是：1）比较有足够的免疫抑制生存的SAA患者的比例 随机分配给IST与BMT的患者两年的计数，包括了解任何一个的影响 关于生育能力，生活质量和生物学因素的治疗，2）支持和管理有效的实施， 该RCT的治理和完成，以及3）利用现有系统和专业知识来确保 遵守高质量数据收集。拟议的DCC提供了有效且经验丰富的 利用现有关系和成功提供临床的框架的基础设施 经过15年的试验，包括经验丰富的统计团队。这些资产将确保设计该试验， 以最大的完整性和效率进行分析和进行 有关患有SAA的儿童和年轻人的最佳疗法的知识。