Mount Sinai Core Clinical Consortium for the BMT Clinical Trials Network

BMT 临床试验网络西奈山核心临床联盟

• 批准号: 10657592
• 负责人: JOHN LEVINE
• 金额: $ 17.33万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-27 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10657592
• 关键词: Acute Graft Versus Host Disease; Age; Allogenic; Antithymoglobulin; Biological Markers; Blood; Blood specimen; Bone Marrow Transplantation; Cessation of life; Clinic; Clinical; Clinical Research; Clinical Trials; Clinical Trials Network; Complication; Conduct Clinical Trials; Development; Disease; Dose; Early Diagnosis; Early treatment; Enrollment; Excision; FDA approved; Gastrointestinal tract structure; Goals; Graft Rejection; Hematological Disease; Immunosuppression; Infection; Inflammatory Bowel Diseases; Intervention; Leadership; Life; Mission; Monoclonal Antibodies; Non-Malignant; Patient Selection; Patient-Focused Outcomes; Patients; Prevention; Prevention strategy; Productivity; Refractory; Regimen; Relapse; Research Personnel; Risk; Risk Assessment; Risk Factors; Sickle Cell Anemia; Steroids; Symptoms; T-Cell Depletion; T-Lymphocyte; Tacrolimus; Testing; Transplant Recipients; Transplantation; Underrepresented Minority; conditioning; disorder prevention; gastrointestinal; graft vs host disease; high risk; high risk population; improved; improved outcome; innovation; mortality; novel; participant enrollment; patient stratification; pharmacologic; preference; trafficking; transplant centers

SUMMARY/ABSTRACT The Mount Sinai BMT CTN Consortium combines three large blood and marrow transplant (BMT) centers (Mount Sinai, Vanderbilt, and the Mayo Clinic; >900 total annual including >250 allogeneic BMT) with a strong track record of productivity within the BMT CTN. Our consortium possesses significant strengths to accomplish BMT CTN strategic goals including long-standing scientific leadership of the BMT CTN, high accrual to BMT CTN clinical trials, a proven ability to enroll large numbers of under-represented minorities in clinical trials, extensive expertise in transplant for non- malignant blood diseases (especially sickle cell disease), and a highly innovative, biomarker-based approach to graft versus host disease (GVHD), the principal complication of allogeneic BMT. Our investigators have developed and validated a novel GVHD-biomarker based score that stratifies patients on the basis of blood samples obtained seven days after BMT that separates patients into low risk and high risk groups for risk of severe GVHD and six month non-relapse mortality (NRM). The day 7 score accurately assigns risk regardless of donor type, degree of HLA-match, conditioning regimen, age, or use of thymoglobulin, making it ideal for testing a preemptive GVHD strategy in the multicenter BMT CTN setting. The majority of deaths in patients with a high risk day 7 score are due to steroid refractory gastrointestinal (GI) GVHD even though symptoms only occur weeks later. We thus propose a preemptive clinical trial to reduce steroid refractory GVHD in high risk patients. We expect such preemption will not increase relapse or deaths from other causes and thereby improve survival. To accomplish this goal, we propose to preemptively treat high risk patients with vedolizumab, a monoclonal antibody that targets α4β7+ T cells and inhibits their trafficking to the GI tract. Vedolizumab is FDA approved for inflammatory bowel disease and has already successfully been used in a small number of BMT patients with steroid refractory GI GVHD. A desirable attribute of our proposal is that testing this strategy in the patients most likely to develop steroid refractory GVHD will require fewer subjects to detect a beneficial effect. Our specific aims are: (1) To participate vigorously in BMT CTN clinical trials and committees and (2) To preemptively treat biomarker-defined high risk patients with vedolizumab to improve one-year steroid-refractory GVHD-free, relapse-free survival. RELEVANCE: The Blood and Marrow Transplant Clinical Trials Network conducts clinical trials to improve outcomes for patients facing life-threatening diseases. The Mount Sinai BMT CTN Consortium will advance the mission of the BMT CTN by enrolling patients onto BMT CTN clinical trials and providing scientific leadership to the BMT CTN. The proposed clinical trial will mitigate graft-versus-host disease, the most serious BMT complication.

摘要/文摘

项目成果

System Level Informatics to Improve Triage Practices for Sickle Cell Disease Vaso-Occlusive Crisis: A Cluster Randomized Controlled Trial.

改善镰状细胞病血管闭塞危机分诊实践的系统级信息学：集群随机对照试验。

• DOI: 10.1016/j.jen.2021.05.007
• 发表时间: 2021
• 期刊: Journal of emergency nursing
• 影响因子: 1.7
• 作者: Linton,Elizabeth;Souffront,Kimberly;Gordon,Lauren;Loo,GeorgeT;Genes,Nicholas;Glassberg,Jeffrey
• 通讯作者: Glassberg,Jeffrey