Improving the Outcomes of Stem Cell Transplantation

改善干细胞移植的结果

• 批准号: 8485632
• 负责人: RICHARD E. CHAMPLIN
• 金额: $ 16.35万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-05 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8485632
• 关键词: Acute Graft Versus Host Disease; Adverse event; Allogenic; Antithymoglobulin; Biological Markers; Blood; Blood Platelets; Calcineurin inhibitor; Cancer Center; Clinical; Clinical Research; Clinical Trials Network; Commit; Complication; Comprehensive Cancer Center; Databases; Development; Disease; Engraftment; Etanercept; Future; Goals; Graft Rejection; Hematologic Neoplasms; Hematopoietic; Hematopoietic Stem Cell Transplantation; Immune; Immunosuppressive Agents; Incidence; Infection; Instruction; Life; Malignant - descriptor; Marrow; Metabolic; Methotrexate; Michigan; Morbidity - disease rate; Multicenter Trials; Outcome; Patients; Pentostatin; Phase; Prevention approach; Prevention strategy; Procedures; Prophylactic treatment; Prospective Studies; Randomized; Regimen; Relapse; Stem cell transplant; Testing; Therapeutic; Time; Toxic effect; Translational Research; Transplantation; Universities; University of Texas M D Anderson Cancer Center; arm; chronic graft versus host disease; effective therapy; graft failure; graft vs host disease; high risk; improved; mortality; neutrophil; novel; outcome forecast; phase 2 study; phase 3 study; standard of care; success; trial comparing

Hematopoietic stem cell transplantation is an effective treatment for a broad range of hematologic, immune, metabolic and malignant diseases. This Is a high-risk procedure which may be complicated by graft-vs.-host disease, graft rejection, regimen related toxicities and infectious complications. Improved therapeutic strategies are needed to improve the outcome and reduce the toxicities. Graft-vs.-host disease is the major complication limiting the broader application of hematopoietic transplantation and novel, more effective therapy is needed. Specific Aim: We propose a Phase II Randomized, Multicenter Trial Comparing Standard GVIHD Prophylaxis with Etanercept vs. Pentostatin/ATG in Unrelated Donor HCT. This is a multicenter prospective study to examine two promising approaches for prevention of GVHD, with the pentostatin arm derived from a large phase l/ll study at our center(Parmar, et al 2010) and the etanercept arm developed with collaborators at the University of Michigan. The proposed study will test the hypothesis that the addition of etanercept or pentostatin/ATG to standard GVHD prophylaxis will improve 6-month NRM rates for patients undergoing matched unrelated HCT for the treatment of hematologic malignancies when compared to historical rates from the CIBMTR database with standard of care GVHD prophylaxis. The primary endpoint for this trial will be NRM at 6 months post-transplant. Secondary endpoints are two-year survival from the time of transplant, incidences of neutrophil and platelet engraftment, graft failure, acute graft-versus-host disease (GVHD), chronic GVHD, current immunosuppressive free survival, relapse, infections, and adverse events. Biologic correlates will be assessed to predict development of GVHD and its prognosis. The goal is to identify the most promising regimen for further definitive testing in a future Phase III study. The application is a competitive renewal of the University of Texas- MD Anderson Cancer Center (MDACC) as a Core Clinical Center for Blood and Marrow Transplant-Clinical Trials Network. MDACC is the nation's largest NCI designated Comprehensive Cancer Center, and a leader in clinical and translational research in hematopoietic transplantation. We are committed to the success of the BMT-CTN and continue to be leaders in the organization. We are a major contributor to the development of BMT-CTN studies and active accrue patients to its studies.

造血干细胞移植是治疗多种血液病、 免疫、代谢和恶性疾病。这是一个高风险的程序，可能会因以下原因而变得复杂 移植物抗宿主病、移植物排斥、治疗相关毒性和感染并发症。 需要改进的治疗策略来改善结果并减少毒性。 移植物抗宿主病是限制造血技术广泛应用的主要并发症 需要移植和新的、更有效的治疗方法。具体目标：我们提出第二阶段 随机、多中心试验比较标准 GVIHD 预防依那西普与普通 GVIHD 的比较 无关供体 HCT 中的喷司他汀/ATG。这是一项多中心前瞻性研究，旨在检验两个 预防 GVHD 的有前途的方法，喷司他丁臂源自大型 l/ll 期研究 在我们的中心（Parmar 等人，2010）以及与大学合作者开发的依那西普臂 密歇根州。拟议的研究将检验以下假设：添加依那西普或喷司他丁/ATG 标准 GVHD 预防将改善接受匹配非亲缘关系患者的 6 个月 NRM 率 与 CIBMTR 的历史比率相比，HCT 治疗血液系统恶性肿瘤的效果 具有 GVHD 预防护理标准的数据库。该试验的主要终点为 6 时的 NRM 移植后几个月。次要终点是移植后两年的生存率、 中性粒细胞和血小板植入、移植失败、急性移植物抗宿主病 (GVHD)、慢性 GVHD、 目前的无免疫抑制生存、复发、感染和不良事件。生物学相关性将是 评估以预测 GVHD 的发生及其预后。目标是确定最有前途的 方案，以便在未来的 III 期研究中进一步确定测试。 该申请是德克萨斯大学MD安德森癌症中心的竞争性更新 (MDACC) 作为血液和骨髓移植临床试验网络的核心临床中心。 MDACC 是 美国最大的 NCI 指定综合癌症中心，临床和转化领域的领导者 主要从事造血移植研究。我们致力于 BMT-CTN 的成功并继续 成为组织中的领导者。我们是 BMT-CTN 研究发展的主要贡献者 积极吸引患者参与其研究。