The Ohio State University Blood and Marrow Transplant Research Consortium

俄亥俄州立大学血液和骨髓移植研究联盟

• 批准号: 10657582
• 负责人: Sumithira Vasu
• 金额: $ 17.35万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-26 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10657582
• 关键词: AMD3100; Acute; Address; Adult; Allogenic; Allografting; Base Sequence; Benign; Blood; Bone Marrow; Bone Marrow Transplantation; CD34 gene; CXCR4 gene; Cell Transplantation; Cells; Clinical Trials Network; Collaborations; Conduct Clinical Trials; Data; Dendritic Cells; Disease; Engraftment; Funding; Future; Genes; Granulocyte Colony-Stimulating Factor; Hematology; Hematopoietic; Immune; Immune System Diseases; Immune system; Immunity; Infection; Kinetics; Lead; Leadership; Longevity; Malignant - descriptor; Malignant Neoplasms; Methods; Mission; Morbidity - disease rate; National Clinical Trials Network; Natural Killer Cells; Ohio; Opportunistic Infections; Outcome; Patients; Process; Productivity; Quality of life; Randomized; Recovery; Relapse; Reporting; Research; Research Personnel; Safety; Science; Siblings; Source; Testing; Therapeutic immunosuppression; Toxic effect; Transplant Recipients; Transplantation; Universities; Work; antagonist; chronic graft versus host disease; curative treatments; donor stem cell; experience; graft failure; graft vs host disease; hematopoietic cell transplantation; high risk; immune reconstitution; improved; member; novel; novel strategies; older patient; peripheral blood; phase 2 study; phase III trial; preference; primary endpoint; reconstitution; secondary endpoint; success; symposium; transplant centers; AMD3100; Acute; Address; Adult; Allogenic; Allografting; Base Sequence; Benign; Blood; Bone Marrow; Bone Marrow Transplantation; CD34 gene; CXCR4 gene; Cell Transplantation; Cells; Clinical Trials Network; Collaborations; Conduct Clinical Trials; Data; Dendritic Cells; Disease; Engraftment; Funding; Future; Genes; Granulocyte Colony-Stimulating Factor; Hematology; Hematopoietic; Immune; Immune System Diseases; Immune system; Immunity; Infection; Kinetics; Lead; Leadership; Longevity; Malignant - descriptor; Malignant Neoplasms; Methods; Mission; Morbidity - disease rate; National Clinical Trials Network; Natural Killer Cells; Ohio; Opportunistic Infections; Outcome; Patients; Process; Productivity; Quality of life; Randomized; Recovery; Relapse; Reporting; Research; Research Personnel; Safety; Science; Siblings; Source; Testing; Therapeutic immunosuppression; Toxic effect; Transplant Recipients; Transplantation; Universities; Work; antagonist; chronic graft versus host disease; curative treatments; donor stem cell; experience; graft failure; graft vs host disease; hematopoietic cell transplantation; high risk; immune reconstitution; improved; member; novel; novel strategies; older patient; peripheral blood; phase 2 study; phase III trial; preference; primary endpoint; reconstitution; secondary endpoint; success; symposium; transplant centers

Project Summary While HCT offers potentially curative therapy to patients with a variety of benign and malignant diseases, both acute and chronic graft versus host disease (GVHD) continue to plague the field and often limit the longevity and quality of life of our patients. While either bone marrow (BM) or mobilized peripheral blood (MPB) are suitable sources of donor hematopoietic cells, this network established in BMT CTN 0201 that granulocyte colony stimulating factor (G-CSF) MPB is associated with a higher risk of chronic GVHD (cGVHD) and worse quality of life following unrelated donor HCT compared to BM. Similar results have been demonstrated in recipients of MPB from matched siblings. The Ohio State Blood and Marrow Transplant Research Consortium (OSUBMT- RC) is comprised of five highly experienced transplant centers with a well-established track record of productivity conducting clinical trials. Our consortium proposes a novel approach to limiting GVHD following HCT by establishing a new standard for the procurement of donor hematopoietic cells for transplantation. The OSUBMT- RC PI has pioneered a novel method to procure donor cells for HCT using the CXCR4 antagonist plerixafor without G-CSF. Plerixafor mobilizes CD34+ cells and other immune cells for transplantation far more rapidly than G-CSF (1 vs 5 days), with less toxicity to the donor. Grafts procured following plerixafor alone (P-MPB) promote full engraftment and based on a recent multi-center phase II study led by the PI, appear to reconstitute immunity faster than G-MPB and may cause less chronic GVHD (cGVHD). These advantages appear to be particularly striking in older patients receiving reduced intensity allografts. Based on these data, we hypothesize that P-MPB will become a suitable and possibly preferable alternative method to procure MPB for HCT due to the combination of better convenience and less toxicity for donors and less GVHD combined with better immune reconstitution in recipients. We propose to test these hypotheses with the following specific aims: Aim 1: We will conduct a randomized Phase II study of P-MPB versus G-MPB in recipients of matched sibling donor allografts with cGVHD-free, relapse free survival as the primary endpoint. Aim 2: We will test the hypothesis that immune reconstitution is improved with P-MPB versus G-MPB through correlative phenotypical, functional, and gene sequence based studies of T, B, NK, and dendritic cells procured from allograft recipients following HCT The proposed study addresses several key priorities of the BMT CTN established at the 2014 State of the Science Symposium and if promising will pave the way for a future definitive Phase III trial that could radically improve our process for collecting allografts from donors.

项目摘要 HCT为患有多种良性和恶性疾病的患者提供了潜在的治疗疗法，但两者都可以 急性和慢性移植与宿主疾病（GVHD）继续困扰着该领域，并且经常限制寿命和寿命 我们患者的生活质量。而骨髓（BM）或动员外周血（MPB）是合适的 供体造血细胞的来源，在BMT CTN 0201中建立的该网络是粒细胞菌落 刺激因子（G-CSF）MPB与慢性GVHD（CGVHD）的风险更高，质量较差 与BM相比，无关的供体HCT的生活。在接受者中也证明了类似的结果 来自匹配的兄弟姐妹的MPB。俄亥俄州的血液和骨髓移植研究联盟（OSUBMT- RC）由五个经验丰富的移植中心组成，其生产率有良好的记录 进行临床试验。我们的财团提出了一种新颖的方法来限制HCT之后的GVHD 建立一个新的标准，用于采购供体造血细胞进行移植。 osubmt- RC PI率先使用CXCR4拮抗剂Plerixafor采购供体细胞的新方法来为HCT采购供体细胞 没有G-CSF。 Plerixafor动员CD34+细胞和其他免疫细胞进行移植的速度要比 G-CSF（1 vs 5天），对供体的毒性较小。单独使用Plerixafor（P-MPB）采购的移植物促进 完全植入和根据PI领导的最近的多中心II期研究，似乎重新建立了免疫力 比G-MPB快，可能导致慢性GVHD（CGVHD）。这些优势似乎特别是 在接受同种异体强度降低的老年患者中罢工。基于这些数据，我们假设P-MPB 由于 更好的便利性和对捐助者的毒性较小，而GVHD较少的毒性结合在一起，结合了更好的免疫力 在接受者中重建。我们建议以以下特定目的检验这些假设： 目标1：我们将在匹配的接受者中对P-MPB与G-MPB进行随机II期研究 具有无CGVHD，无复发生存的同种异体移植物作为主要终点。 AIM 2：我们将测试以下假设，即通过P-MPB与G-MPB改善免疫重构 通过基于T，B，NK和树突状的基于相关表型，功能和基因序列的研究 HCT后从同种异体移植受者中采购的细胞 拟议的研究介绍了2014年在2014年确定的BMT CTN的几个关键优先事项 科学专题讨论会，如果有前途的话，将为将来的确定阶段III铺平道路，该试验可能会从根本上开始 改善我们从捐助者那里收集同种异体移植的过程。