Improving the Outcomes of Stem Cell Transplantation

改善干细胞移植的结果

• 批准号: 8314033
• 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/8314033
• 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.

造血干细胞移植是一种有效治疗多种血液病、 免疫、代谢和恶性疾病。这是一个高风险的程序，可能会复杂化， 移植物vs.宿主疾病、移植排斥、方案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降低毒性。 移植物vs.宿主疾病是限制造血干细胞广泛应用的主要并发症 移植和新的，更有效的治疗是必要的。具体目标：我们提出第二阶段 随机、多中心试验，比较依那西普与 无关供体HCT中的Pentostatin/ATG。这是一项多中心前瞻性研究， 预防GVHD的有希望的方法，其中喷司他丁组来自大型I/II期研究 在我们的中心（Parmar，et al 2010）和依那西普臂开发与合作者在大学 密歇根该拟议的研究将检验以下假设： 标准的GVHD预防将改善接受匹配的非相关性移植的患者的6个月NRM率。 与CIBMTR的历史发生率相比，用于治疗血液系统恶性肿瘤的HCT 数据库与标准护理GVHD预防。本试验的主要终点为6时的NRM 移植后几个月。次要终点是移植后2年生存率， 中性粒细胞和血小板植入，移植物衰竭，急性移植物抗宿主病（GVHD），慢性GVHD， 当前无免疫抑制生存期、复发、感染和不良事件。生物相关性将是 评估以预测GVHD的发展及其预后。我们的目标是找出最有希望的 在未来的III期研究中进行进一步的确定性测试。 该申请是德克萨斯大学医学博士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指定的综合癌症中心，以及临床和转化的领导者 研究造血移植。我们致力于BMT-CTN的成功，并继续 成为组织的领导者。我们是BMT-CTN研究发展的主要贡献者， 积极吸引患者参加其研究。