vedolizumab in the prophylaxis of intestinal acute graft versus host disease (agvhd) in participants undergoing allogeneic hematopoietic stem cell (allo-hsct) transplantation

Conditions: Hematopoietic Stem Cells

Summary: the purpose of this study is to evaluate the efficacy of vedolizumab when added to background agvhd prophylaxis regimen compared to placebo and background agvhd prophylaxis regimen on intestinal agvhd-free survival by day +180 in participants who receive allo-hsct as treatment for a hematologic malignancy or myeloproliferative disorder.

the drug being tested in this study is called vedolizumab. vedolizumab is being tested to treat people who are undergoing allo-hsct transplantation. this study will look at the efficacy and safety of vedolizumab in the prophylaxis of intestinal agvhd in participants undergoing allo-hsct transplantation. the study will enroll approximately 558 participants. participants will be randomly assigned (by chance, like flipping a coin) in 1:1 ratio to one of the two treatment groups-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need) along with background gvhd prophylaxis regimen: * vedolizumab 300 mg * placebo (dummy inactive intravenous infusion) this multi-center trial will be conducted worldwide. the overall time to participate in this study is 12 months.

Eligibility criteria:
inclusion criteria: 1. must be \>= 18 years of age and, in selected countries, adolescents aged 12 years and greater and weighing \>=30 kilogram (kg) at time of randomization. 2. must undergo deoxyribose nucleic acid (dna)-based human leukocyte antigen (hla) matching and be 8 of 8 or 7 of 8 hla-matched (singe allele or antigen mismatch at hla-a, -b, and -c, and hla-drb1 is allowable) unrelated hematopoietic stem cell transplantation (hsct) from either peripheral blood or bone marrow stem cells for a hematologic malignancy or myeloproliferative disorder. 3. for whom a myeloablative conditioning or reduced intensity conditioning (ric) is planned. 4. allo-hsct eligible (meeting institutional criteria)-participants planned medical care should include agvhd prophylaxis with a combination of calcineurin inhibitor (cni) (cyclosporine \[cys\] or tacrolimus \[tac\]) and methotrexate (mtx) or cni and mycophenolate mofetil (mmf). with the exception of antithymocyte globulin (atg) (antithymocyte globulin-fresenius \[atg-f\] or thymoglobulin), all other therapies, approved or investigational, for gvhd prophylaxis are excluded. 5. eastern cooperative oncology group (ecog) performance status of \ =18 years at randomization or \>=60 % using the karnofsky performance status for adolescent participants aged \>=16 years at randomization or the lansky performance status for adolescent participants aged 12 to \< 16 years at randomization. exclusion criteria: 1. had prior allo- hsct. 2. planned umbilical cord blood transplant or planned to receive posttransplant cyclophosphamide, in vivo or ex vivo t cell-depleted hematopoietic stem cells (hscs) with the exception of atg (atg-f or thymoglobulin). 3. planned allo-hsct for nonmalignant hematological disorders (example, aplastic anemia, sickle cell anemia, thalassemias, fanconi anemia or immunodeficiency).

Keywords: drug therapy