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
- Interventions
- Registration Number
- NCT03657160
- Lead Sponsor
- Millennium Pharmaceuticals, Inc.
- Brief 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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 343
- 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.
- 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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Vedolizumab 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). Vedolizumab 300 mg Vedolizumab 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).
- Primary Outcome Measures
Name Time Method Intestinal aGvHD-Free Survival After Allo-HSCT by +180 Days 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.
- Secondary Outcome Measures
Name Time Method 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 Grade B-D aGvHD Free Survival is the time from the date of first study drug administration (Day-1) to aGvHD event or death, where an event is defined as death or grade B-D any organ involvement per IBMTR Severity Index for aGvHD.
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 Intestinal aGvHD and Relapse Free Survival is the time from the date of first study drug administration (Day-1) to intestinal aGvHD event/death/relapse, where an event is defined as death or Stage 1-4 intestinal involvement per Acute Graft versus-Host Disease Clinical Stage criteria, or relapse. It will be censored for participants who have not had the event or have had the event after pre-specified timing, e.g., last contact or Day +180 after allo-HSCT whichever occurs first.
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 Grade C-D aGvHD Free Survival is the time from the date of first study drug administration (Day-1) to GvHD event/death, where an event is defined as Grade C-D aGvHD any organ involvement per International Bone Marrow Transplant Registry Database (IBMTR) Severity Index for aGvHD or death. It will be censored for participants who have not had the event or have had the event after pre-specified timing, eg, last contact or Day +180 after allo-HSCT whichever occurs first.
Nonrelapse Mortality (NRM) From the date of first dose of study drug to first documented death without relapse, up to Day +180 Non-relapse mortality is the time from the date of first study drug administration (Day-1) to death without occurrence of a relapse. Data was censored for participants who have not had the event or have had the event after pre-specified timing, e.g., last contact or Day +180 after allo HSCT whichever occurs first.
Overall Survival (OS) From the date of first dose of study drug to first documented death up to Day +180 Overall Survival by Days +180 is the time from the date of first study drug administration (Day-1) to death from any cause.
Trial Locations
- Locations (139)
Children's Healthcare of Atlanta
🇺🇸Atlanta, Georgia, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
National Research Center for Hematology
🇷🇺Moscow, Russian Federation
Fundacion Favaloro Hospital Universitario
🇦🇷Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina
Universitatsspital Zurich
🇨🇭Zurich, Switzerland
University of North Carolina Hospitals
🇺🇸Chapel Hill, North Carolina, United States
Oslo University Hospital - Rikshospitalet
🇳🇴Oslo, Norway
Cardiff and Vale University Health Board
🇬🇧Cardiff, Wales, United Kingdom
Sheffield Teaching Hospitals NHS Foundation Trust
🇬🇧Sheffield, England, United Kingdom
Hospital Universitario de Gran Canaria Doctor Negrin
🇪🇸Las Palmas De Gran Canaria, LAS Palmas, Spain
Buddhist Tzu Chi General Hospital
🇨🇳Hualien City, Hualien, Taiwan
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Pomorskie, Poland
Spitalul Clinic Judetean de Urgenta Targu Mure
🇷🇴Târgu-Mureş, Mures, Romania
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
Austin Health
🇦🇺Heidelberg, Victoria, Australia
Hospital Universitario Walter Cantidio - Universidade Federal do Ceara
🇧🇷Fortaleza, Ceara, Brazil
Hospital de Cancer de Barretos
🇧🇷Barretos, SAO Paulo, Brazil
The Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
Centre Hospitalier Universitaire Nantes - Hotel Dieu
🇫🇷Nantes Cedex 1, PAYS DE LA Loire, France
Universitatsklinikum Carl Gustav Carus Dresden
🇩🇪Dresden, Sachsen, Germany
Diakonie-Klinikum Stuttgart
🇩🇪Stuttgart, Baden-wuerttemberg, Germany
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
The Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
Universitair Ziekenhuis Leuven
🇧🇪Leuven, Flemish Brabant, Belgium
Skanes Universitetssjukhus i Lund
🇸🇪Lund, Skane, Sweden
Saskatchewan Cancer Agency
🇨🇦Saskatoon, Saskatchewan, Canada
Hopital Necker-Enfants Malades
🇫🇷Paris, Ile-de-france, France
Centre Hospitalier Universitaire Amiens-Picardie
🇫🇷Amiens, Picardie, France
Instituto Brasileiro de Controle do Cancer - Sao Camilo Oncolgia
🇧🇷Sao Paulo, Brazil
Universitatsmedizin Mannheim
🇩🇪Mannheim, Baden-wuerttemberg, Germany
Hospital General Universitario Morales Meseguer
🇪🇸Murcia, Spain
Istituto Clinico Humanitas Humanitas Cancer Center
🇮🇹Milano, Italy
Karolinska Universitetssjukhuset
🇸🇪Stockholm, Sweden
Hopital Saint Louis
🇫🇷Paris Cedex 10, Ile-de-france, France
Hospital Santa Marcelina
🇧🇷Sao Paulo, Brazil
Universitatsklinikum Frankfurt
🇩🇪Frankfurt am Main, Hessen, Germany
Hokkaido University Hospital
🇯🇵Sapporo-shi, Hokkaido, Japan
Azienda Ospedaliera Cardinale G. Panico
🇮🇹Tricase, Lecce, Italy
Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
🇮🇹Milano, Italy
Hopital Saint-Antoine
🇫🇷Paris, Ile-de-france, France
Groupe Hospitalier Pitie-Salpetriere
🇫🇷Paris, Ile-de-france, France
Rambam Health Care Campus - Rambam Medical Center
🇮🇱Haifa, Israel
Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital
🇯🇵Nagoya, Aichi, Japan
Ospedale Mazzoni
🇮🇹Ascoli Piceno, Marche, Italy
Policlinico Universitario di Catania
🇮🇹Catania, Italy
Hadassah Medical Center
🇮🇱Jerusalem, Israel
Soroka University Medical Center
🇮🇱Beer Sheva, Beersheba, Israel
Azienda Grande Ospedale Metropolitano Bianchi Melacrino Morelli
🇮🇹Reggio Calabria, Calabria, Italy
Instituto Portugues de Oncologia de Lisboa Francisco Gentil
🇵🇹Lisboa, Portugal
Centro Hospitalar de Lisboa Norte EPE- Hospital Santa Maria
🇵🇹Lisboa, Portugal
National University Hospital
🇸🇬Singapore, Singapore
Kaohsiung Medical University Hospital
🇨🇳Kaohsiung, Taiwan
Kyushu University Hospital
🇯🇵Fukuoka-shi, Fukuoka, Japan
The Catholic University of Korea - Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Universitaetsklinikum Schleswig-Holstein - Campus Kiel
🇩🇪Kiel, Schleswig-holstein, Germany
Fiona Stanley Hospital
🇦🇺Murdoch, Western Australia, Australia
Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital
🇯🇵Hiroshima-shi, Hiroshima, Japan
Osaka City University Hospital
🇯🇵Osaka, Japan
Severance Hospital
🇰🇷Seoul, Korea, Republic of
David Geffen School of Medicine at University of California Los Angeles
🇺🇸Los Angeles, California, United States
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
🇺🇸Chicago, Illinois, United States
Augusta University Georgia Cancer Center
🇺🇸Augusta, Georgia, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
University of Kentucky Chandler Medical Center
🇺🇸Lexington, Kentucky, United States
Marlene and Stewart Greenebaum Cancer Center
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Roswell Park Comprehensive Cancer Center
🇺🇸Buffalo, New York, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
Columbia University Medical Center - The Columbia Center for Translational Immunology
🇺🇸New York, New York, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Texas Oncology - Baylor Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States
Hospital Privado Centro Medico de Cordoba
🇦🇷Cordoba, Argentina
Massey Cancer Center
🇺🇸Richmond, Virginia, United States
Hospital Italiano de Buenos Aires
🇦🇷Ciudad Autonoma de Buenos Aires, Argentina
Royal Brisbane and Women's Hospital
🇦🇺Herston, Queensland, Australia
Saint Vincent's Hospital Sydney
🇦🇺Darlinghurst, New South Wales, Australia
Ziekenhuisnetwerk Stuivenberg
🇧🇪Antwerpen, Belgium
Fundacao Antonio Prudente - A.C.Camargo Cancer Center
🇧🇷Sao Paulo, Brazil
Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo
🇧🇷Sao Paulo, Brazil
Instituto do Cancer e Transplante de Curitiba
🇧🇷Curitiba, Parana, Brazil
Centre Hospitalier Universitaire de Limoges
🇫🇷Limoges Cedex, Limousin, Lorraine, France
Universitatsmedizin der Johannes Gutenberg Universitat Mainz
🇩🇪Mainz, Rheinland-pfalz, Germany
Universitatsklinikum Halle
🇩🇪Halle, Sachsen-anhalt, Germany
University Regional General Hospital of Patras
🇬🇷Patras, Peloponnese, Greece
Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona
🇮🇹Ancona, Italy
Ospedale dell'Angelo
🇮🇹Mestre, Venezia, Italy
Azienda Ospedaliera Policlinico di Bari
🇮🇹Bari, Italy
Presidio Ospedaliero di Pescara
🇮🇹Pescara, Italy
Okayama University Hospital
🇯🇵Okayama-city, Okayama, Japan
Shizuoka Cancer Center
🇯🇵Nagaizumi, Shizuoka, Japan
Jichi Medical University Hospital
🇯🇵Shimotsuke-city, Tochigi, Japan
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Gyeonggi-do, Korea, Republic of
Kyungpook National University Hospital
🇰🇷Daegu, Gyeongsangbuk-do, Korea, Republic of
Keimyung University Dongsan Hospital
🇰🇷Daegu, Gyeongsangbuk-do, Korea, Republic of
Pusan National University Hospital
🇰🇷Busan, Gyeongsangnam-do, Korea, Republic of
Daegu Catholic University Medical Center
🇰🇷Daegu, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Instituto Portugues de Oncologia do Porto Francisco Gentil
🇵🇹Porto, Portugal
Sverdlovsk Regional Clinical Hospital #1
🇷🇺Ekaterinburg, Sverdlovsk, Russian Federation
Institutul Clinic Fundeni
🇷🇴Bucuresti, Romania
Hospital Universitari Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Hospital Universitario Ramon Y Cajal
🇪🇸Madrid, Spain
Hospital Universitario Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital Universitario Virgen de la Arrixaca
🇪🇸Murcia, Spain
Hospital Universitario de Salamanca
🇪🇸Salamanca, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Universitatsspital Basel
🇨🇭Basel, Switzerland
China Medical University Hospital
🇨🇳Taichung, Taiwan
Koo Foundation Sun Yat-Sen Cancer Center
🇨🇳Taipei, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Chang Gung Memorial Hospital
🇨🇳Taoyuan, Taiwan
Imperial College Healthcare NHS Trust
🇬🇧London, England, United Kingdom
Barts Health NHS Trust
🇬🇧London, England, United Kingdom
Emory University - Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Cohen Children's Medical Center
🇺🇸New Hyde Park, New York, United States
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Indiana University Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
University of Virginia Health System
🇺🇸Charlottesville, Virginia, United States
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Chungnam National University Hospital
🇰🇷Daejeon, Korea, Republic of
Ordensklinikum Linz Elisabethinen
🇦🇹Linz, Upper Austria, Austria
University of Alabama at Birmingham Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States
Mayo Clinic - Rochester
🇺🇸Rochester, Minnesota, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital
🇯🇵Bunkyo-Ku, Tokyo, Japan
Hopital Pontchaillou
🇫🇷Rennes Cedex 9, Bretagne, France
University General Hospital of Athens Attikon
🇬🇷Athens, Attica, Greece
Debreceni Egyetem Klinikai Kozpont
🇭🇺Debrecen, Hajdu-bihar, Hungary
Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
🇲🇽Monterrey, Nuevo LEON, Mexico
Singapore General Hospital
🇸🇬Singapore, Singapore
Raffles Hospital
🇸🇬Singapore, Singapore
Clinica Universidad de Navarra
🇪🇸Pamplona, Navarra, Spain
The Clatterbridge Cancer Centre NHS Foundation Trust
🇬🇧Liverpool, England, United Kingdom