Blood and Marrow Transplant Clinical Trials Network

血液和骨髓移植临床试验网络

• 批准号: 9385494
• 负责人: JOANNE KURTZBERG
• 金额: $ 16.92万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9385494
• 关键词: Academic Medical Centers; Acute; Acute Graft Versus Host Disease; Address; Adoption; Adult; Allogenic; Applications Grants; Behavior Therapy; Blood; Blood Cells; Blood Platelets; Blood donor; Bone Marrow Transplantation; CD4 Lymphocyte Count; Cells; Child; Childhood; Childhood Leukemia; Chimerism; Clinical; Clinical Trials; Clinical Trials Network; Communities; Cyclophosphamide; Data; Data Analyses; Data Coordinating Center; Disease; Disease-Free Survival; Donor Selection; Dose; Engraftment; Enrollment; Foundations; Funding; Hematologic Neoplasms; Hematopoietic; Hematopoietic Stem Cell Transplantation; Hospitalization; Immune; Immunologics; Incidence; Manuscripts; Marrow; Medical center; Methods; Mission; Modeling; Multi-Institutional Clinical Trial; National Heart, Lung, and Blood Institute; Non-Malignant; Outcome; Patients; Pediatric Oncologist; Phase; Phase II Clinical Trials; Preparation; Prophylactic treatment; Protocols documentation; Randomized; Randomized Clinical Trials; Refractory; Regimen; Relapse; Reporting; Research Infrastructure; Research Personnel; Research Proposals; Residual Neoplasm; Risk; Role; Severities; Site; Source; Specimen; Standardization; Support Groups; Supportive care; T-Cell Depletion; Time; Tissues; Transplantation; Umbilical Cord Blood; Umbilical Cord Blood Transplantation; Work; arm; base; blood group; chronic graft versus host disease; conditioning; experience; fludarabine; follow-up; graft vs host disease; high risk; high risk population; in vivo; innovation; interest; leukemia; meetings; mortality; neutrophil; novel strategies; open label; pediatric patients; programs; prospective; reconstitution; success; symposium; trial comparing

Abstract The pediatric and adult transplant programs at Duke University Medical Center have served as a core clinical center for the BMT-CTN since its establishment in 2001. As a core center, Duke has made significant contributions to the network, including enrollment of 310 patients on CTN protocols, chairing two protocols (Dr. Kurtzberg chaired 0501 and Dr. Horwitz chaired 0901); serving on 6 protocol committees and 2 disease committees, authoring manuscripts and establishing and managing the immune reconstitution core for protocol 0501. The center has been in compliance with accurate and timely data and bio-specimen submission. The PI and Co-PI have regularly attended steering committee meetings, conference calls and the SSOS meetings. For this renewal of the BMT-CTN, Duke brings three specialized types of expertise to the table, (1) a long- standing and pioneering role in cord blood transplantation and banking and (2) unique experience in the treatment of pediatric patients with hematopoietic stem cell transplantation for non-malignant diseases and (3) pioneering work in cord blood and cord-tissue derived cellular therapies. In this application, Duke has added two additional centers as part of a Duke Consortium to increase participation in the network and also to increase accrual to BMT-CTN trials. The study concept proposed in this application, will serve as the foundation for a follow-on study to BMT-CTN 0501. The clinical trial proposed will compare in a randomized phase II clinical trial, the outcomes of related haplo-identical bone marrow transplantation or unrelated donor cord blood transplantation in children with high risk leukemias undergoing myeloablative conditioning therapy. The supportive care will be standardized. The preparative regimens and GvHD prophylaxis will be based on treatment `packages' well studied for the cord blood group and piloted for the haplo-BMT group. They are standardized to the extent possible, with the splitting cyclophosphamide for pre and post-transplant dosing for the haplo group and use of fludarabine in the cord blood group. The primary endpoint will be relapse-free survival at 2 years post-transplant. Overall survival, engraftment, acute and chronic Graft-versus-Host Disease, treatment related mortality, immune reconstitution, and transplant feasibility will also be explored as secondary endpoints. The predictive role of MRD at the time of transplant will also be examined to determine if either graft source offers better protection against post- transplant leukemic relapse. This study will answer critical and timely questions about the role of various alternative donors and identification of best practices for alternative donor selection for transplantation of children with hematological malignancies lacking matched related or unrelated donors. We plan to fund this trial by responding to the FOA Clinical Coordinating Center for Multi-Site Investigator- Initiated Clinical Trials (Collaborative UG3/UH3) PAR-16-300, which is due on February 13, 2017. Dr. Mary Eapen, from the CIBMTR, will serve as the PI for the grant application for the Data Coordinating Center which will utilize the infra-structure already established for the BMT-CTN. We have full support of the group at Johns Hopkins who developed the haplo post-transplant cyclophosphamide approach, The CIBMTR and the pediatric transplant community to conduct this study and prioritize accrual to the trial. Accordingly, we expect to accrue 180 patients in 3-4 years and, with two-year follow-up and data analysis, expect to complete the study in <6 years.

摘要 杜克大学医学中心的儿科和成人移植项目已成为核心临床研究项目， 自2001年成立以来，BMT-CTN中心。作为一个核心中锋，杜克已经做出了重大的贡献。 对网络的贡献，包括登记310名患者的CTN协议，主持两个协议（博士。 Kurtzberg主持0501，Horwitz博士主持0901）;在6个方案委员会和2个疾病委员会任职 委员会，撰写手稿，建立和管理免疫重建核心方案 0501.中心一直遵守准确和及时的数据和生物标本提交。的PI 和Co-PI定期参加指导委员会会议、电话会议和SSOS会议。 对于BMT-CTN的更新，杜克带来了三种专业类型的专业知识，（1）长期- 在脐带血移植和储存方面的地位和先驱作用;（2）在脐带血移植和储存方面的独特经验 用造血干细胞移植治疗非恶性疾病的儿科患者，以及（3） 脐带血和脐带组织衍生细胞疗法的开创性工作。在这份申请中，杜克补充说， 另外两个中心作为杜克联盟的一部分，以增加对网络的参与， 增加BMT-CTN试验的累积。 本申请中提出的研究概念将作为BMT-CTN后续研究的基础 0501.该临床试验将在一项随机II期临床试验中比较， 单倍相合骨髓移植或非血缘脐血移植治疗高血压病 接受清髓性预处理治疗的风险白血病。支持性护理将标准化。的 准备性方案和GvHD预防将基于对脐带血进行了充分研究的治疗“套餐” 血型，并被引导用于单倍-BMT组。它们尽可能标准化， Haplo组在移植前和移植后分次给药环磷酰胺， 脐血血型主要终点是移植后2年的无复发生存率。总生存期， 移植、急性和慢性移植物抗宿主病、治疗相关死亡率、免疫重建， 和移植可行性也将作为次要终点进行探索。MRD在当时的预测作用 还将检查移植物的数量，以确定是否有任何一种移植物来源能更好地保护患者免受术后感染。 移植白血病复发这项研究将回答有关各种因素的作用的关键和及时的问题， 替代供体和确定选择移植替代供体的最佳做法， 缺乏匹配的相关或不相关捐赠者的恶性血液病儿童。 我们计划通过响应FOA多中心研究者临床协调中心来资助这项试验- 启动临床试验（协作UG 3/UH 3）PAR-16-300，到期日为2017年2月13日。玛丽医生 来自CIBMTR的Eapen将担任数据协调中心拨款申请的PI， 将利用已经为BMT-CTN建立的基础设施。我们得到了约翰斯集团的全力支持 霍普金斯开发了移植后单倍体环磷酰胺方法，CIBMTR和儿科 移植社区进行这项研究，并优先考虑增加试验。因此，我们预计， 180例患者在3-4年内完成研究，经过两年随访和数据分析，预计在<6年内完成研究。 年