Blood and Marrow Transplant Clinical Trials Network

摘要 杜克大学医学中心的儿科和成人移植项目一直是核心临床项目 BMT-CTN自2001年成立以来一直是该中心的成员。作为核心中锋，杜克大学取得了重要的成就 对网络的贡献，包括招募310名患者参加CTN方案，主持两个方案(Dr。 库兹伯格担任主席0501，霍维茨博士担任主席(0901)；在6个礼宾委员会和2个疾病委员会任职 委员会，撰写手稿，建立和管理协议的免疫重建核心 0501号。该中心一直在遵守准确和及时的数据和生物标本提交。《少年派》 和共同派定期出席指导委员会会议、电话会议和社会保障组织会议。 对于这次BMT-CTN的更新，杜克大学带来了三种专业类型的专业知识，(1)长期- 在脐带血移植和银行方面的地位和先锋作用以及(2)在 儿童非恶性疾病的造血干细胞移植治疗及(3) 在脐带血和脐带组织衍生细胞疗法方面的开创性工作。在此应用程序中，Duke添加了 作为杜克财团的一部分，增加两个中心，以增加对网络的参与，并 增加BMT-CTN试验的应计费用。 本申请中提出的研究概念将作为BMT-CTN后续研究的基础 0501号。建议的临床试验将在随机的II期临床试验中比较相关的结果 单倍体相合骨髓移植或非亲缘脐血移植治疗高血压病患儿 正在接受清髓性条件治疗的高危白血病。支持性护理将标准化。这个 准备方案和GvHD预防将以对脐带进行充分研究的治疗“一揽子”为基础 血型，并为单骨髓移植组试点。它们被尽可能地标准化，具有 HAPLO组移植前和移植后环磷酰胺的裂解及氟达拉滨的应用 脐带血型。主要终点是移植后2年的无复发存活率。总体存活率， 移植，急、慢性移植物抗宿主病，治疗相关死亡率，免疫重建， 移植的可行性也将作为次要终点进行探索。MRD在当时的预测作用 还将对移植的来源进行检查，以确定其中一种移植物来源是否提供更好的保护，防止术后 移植后白血病复发。这项研究将回答关键和及时的问题，即 替代供体和确定选择替代供体进行移植的最佳做法 患有恶性血液病的儿童缺乏匹配的亲属或非亲属捐赠者。 我们计划通过响应FOA多站点研究人员临床协调中心来资助这项试验- 启动临床试验(Collaborative UG3/UH3)PAR-16-300，截止日期为2017年2月13日。玛丽医生 来自CIBMTR的EAPN将担任数据协调中心拨款申请的PI，该中心 将利用已经为BMT-CTN建立的基础设施。我们在Johns得到了团队的全力支持 霍普金斯发展了移植后环磷酰胺的方法，CIBMTR和儿科 移植社区进行这项研究，并优先考虑试验的收益。因此，我们预计将产生 180名患者在3-4年内完成这项研究，通过两年的随访和数据分析，有望完成研究 好几年了。

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.