Mount Sinai Core Clinical Consortium for the BMT Clinical Trials Network

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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.