A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Vedolizumab in the Prophylaxis of Intestinal Acute Graft Versus-Host Disease in Subjects Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 343
- 试验地点
- 139
- 主要终点
- Intestinal aGvHD-Free Survival After Allo-HSCT by +180 Days
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •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.
- •For whom a myeloablative conditioning or reduced intensity conditioning (RIC) is planned.
- •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.
- •Eastern Cooperative Oncology Group (ECOG) performance status of <= 2 for participants aged >=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.
排除标准
- •Had prior allo- HSCT.
- •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).
- •Planned allo-HSCT for nonmalignant hematological disorders (example, aplastic anemia, sickle cell anemia, thalassemias, Fanconi anemia or immunodeficiency).
研究组 & 干预措施
Placebo
Vedolizumab placebo-matching, intravenous (IV) infusion, once on Day -1 along with background graft-versus-host disease (GvHD) prophylaxis regimen prior to Allo-HSCT and once on Days +13, +41, +69, +97, +125, and +153 post Allo-HSCT up to the end of study treatment (up to 182 days).
干预措施: Vedolizumab Placebo (Drug)
Vedolizumab 300 mg
Vedolizumab 300 mg, IV infusion, once on Day -1 along with background GvHD prophylaxis regimen prior to Allo-HSCT and once on Days +13, +41, +69, +97, +125, and +153 post Allo-HSCT up to the end of study treatment (up to 182 days).
干预措施: Vedolizumab (Drug)
结局指标
主要结局
Intestinal aGvHD-Free Survival After Allo-HSCT by +180 Days
时间窗: From the date of first dose of study drug to first documented intestinal aGvHD or death, whichever occurs first up to +180 days
Intestinal aGvHD Free Survival is the time from the date of first study drug administration (Day-1) to intestinal aGvHD event/death, where an event is defined as death due to any cause or Stage 1-4 intestinal involvement per Acute Graft versus-Host Disease Clinical Stage criteria. Data was censored for participants who have not had the intestinal aGvHD event or died or have had the event after pre-specified timing, e.g., last contact or Day +180 after allo HSCT whichever occurs first.
次要结局
- Grade B-D aGvHD-Free Survival(From the date of first dose of study drug to first documented grade B-D aGvHD or death, whichever occurs first up to Day +180)
- Intestinal aGvHD-Free and Relapse-Free Survival(From the date of first dose of study drug to first documented intestinal aGvHD, death or relapse, whichever occurs first up to Day +180)
- Grade C-D aGvHD-Free Survival(From the date of first dose of study drug to first documented Grade C-D aGvHD or death, whichever occurs first up to Day +180)
- Nonrelapse Mortality (NRM)(From the date of first dose of study drug to first documented death without relapse, up to Day +180)
- Overall Survival (OS)(From the date of first dose of study drug to first documented death up to Day +180)