Vedolizumab in the Prophylaxis of Intestinal Acute Graft Versus Host Disease (aGVHD) in Participants Undergoing Allogeneic Hematopoietic Stem Cell (Allo-HSCT) Transplantation

NCT ID: NCT03657160

Last Updated: 2023-06-06

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

343 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-02-06

Study Completion Date

2022-05-09

Brief Summary

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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

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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.

Conditions

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Hematopoietic Stem Cells

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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).

Group Type PLACEBO_COMPARATOR

Vedolizumab Placebo

Intervention Type DRUG

Vedolizumab placebo-matching IV infusion.

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).

Group Type EXPERIMENTAL

Vedolizumab

Intervention Type DRUG

Vedolizumab IV infusion.

Interventions

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Vedolizumab Placebo

Vedolizumab placebo-matching IV infusion.

Intervention Type DRUG

Vedolizumab

Vedolizumab IV infusion.

Intervention Type DRUG

Other Intervention Names

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MLN0002

Eligibility Criteria

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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 \<= 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.

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).
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Takeda

Locations

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University of Alabama at Birmingham Comprehensive Cancer Center

Birmingham, Alabama, United States

Site Status

David Geffen School of Medicine at University of California Los Angeles

Los Angeles, California, United States

Site Status

Children's Healthcare of Atlanta

Atlanta, Georgia, United States

Site Status

Emory University - Winship Cancer Institute

Atlanta, Georgia, United States

Site Status

Augusta University Georgia Cancer Center

Augusta, Georgia, United States

Site Status

Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Chicago, Illinois, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

University of Kentucky Chandler Medical Center

Lexington, Kentucky, United States

Site Status

Marlene and Stewart Greenebaum Cancer Center

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Mayo Clinic - Rochester

Rochester, Minnesota, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Roswell Park Comprehensive Cancer Center

Buffalo, New York, United States

Site Status

Cohen Children's Medical Center

New Hyde Park, New York, United States

Site Status

Weill Cornell Medical College

New York, New York, United States

Site Status

Columbia University Medical Center - The Columbia Center for Translational Immunology

New York, New York, United States

Site Status

University of North Carolina Hospitals

Chapel Hill, North Carolina, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States

Site Status

University of Virginia Health System

Charlottesville, Virginia, United States

Site Status

Massey Cancer Center

Richmond, Virginia, United States

Site Status

Fundacion Favaloro Hospital Universitario

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

Site Status

Hospital Italiano de Buenos Aires

Buenos Aires, , Argentina

Site Status

Hospital Privado Centro Medico de Cordoba

Córdoba, , Argentina

Site Status

Saint Vincent's Hospital Sydney

Darlinghurst, New South Wales, Australia

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Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

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Austin Health

Heidelberg, Victoria, Australia

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The Royal Melbourne Hospital

Parkville, Victoria, Australia

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Fiona Stanley Hospital

Murdoch, Western Australia, Australia

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Ordensklinikum Linz Elisabethinen

Linz, Upper Austria, Austria

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Universitair Ziekenhuis Leuven

Leuven, Flemish Brabant, Belgium

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Ziekenhuisnetwerk Stuivenberg

Antwerp, , Belgium

Site Status

Hospital Universitario Walter Cantidio - Universidade Federal do Ceara

Fortaleza, Ceará, Brazil

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Instituto do Cancer e Transplante de Curitiba

Curitiba, Paraná, Brazil

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Hospital de Cancer de Barretos

Barretos, São Paulo, Brazil

Site Status

Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo

São Paulo, , Brazil

Site Status

Fundacao Antonio Prudente - A.C.Camargo Cancer Center

São Paulo, , Brazil

Site Status

Instituto Brasileiro de Controle do Cancer - Sao Camilo Oncolgia

São Paulo, , Brazil

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Hospital Santa Marcelina

São Paulo, , Brazil

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CancerCare Manitoba

Winnipeg, Manitoba, Canada

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Saskatchewan Cancer Agency

Saskatoon, Saskatchewan, Canada

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Hopital Pontchaillou

Rennes, Brittany Region, France

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Centre Hospitalier Universitaire de Limoges

Limoges, Limousin, Lorraine, France

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Centre Hospitalier Universitaire Nantes - Hotel Dieu

Nantes, Pays de la Loire Region, France

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Centre Hospitalier Universitaire Amiens-Picardie

Amiens, Picardie, France

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Hopital Saint-Antoine

Paris, Île-de-France Region, France

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Groupe Hospitalier Pitie-Salpetriere

Paris, Île-de-France Region, France

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Hopital Necker-Enfants Malades

Paris, Île-de-France Region, France

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Hopital Saint Louis

Paris, Île-de-France Region, France

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Universitatsmedizin Mannheim

Mannheim, Baden-Wurttemberg, Germany

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Diakonie-Klinikum Stuttgart

Stuttgart, Baden-Wurttemberg, Germany

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Universitatsklinikum Frankfurt

Frankfurt am Main, Hesse, Germany

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Universitatsmedizin der Johannes Gutenberg Universitat Mainz

Mainz, Rhineland-Palatinate, Germany

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Universitatsklinikum Carl Gustav Carus Dresden

Dresden, Saxony, Germany

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Universitatsklinikum Halle

Halle, Saxony-Anhalt, Germany

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Universitaetsklinikum Schleswig-Holstein - Campus Kiel

Kiel, Schleswig-Holstein, Germany

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University General Hospital of Athens Attikon

Athens, Attica, Greece

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University Regional General Hospital of Patras

Patras, Peloponnese, Greece

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Debreceni Egyetem Klinikai Kozpont

Debrecen, Hajdú-Bihar, Hungary

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Soroka University Medical Center

Beersheba, Beersheba, Israel

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Rambam Health Care Campus - Rambam Medical Center

Haifa, , Israel

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Hadassah Medical Center

Jerusalem, , Israel

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The Chaim Sheba Medical Center

Ramat Gan, , Israel

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Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

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Azienda Grande Ospedale Metropolitano Bianchi Melacrino Morelli

Reggio Calabria, Calabria, Italy

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Azienda Ospedaliera Cardinale G. Panico

Tricase, Lecce, Italy

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Ospedale Mazzoni

Ascoli Piceno, The Marches, Italy

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Ospedale dell'Angelo

Mestre, Venezia, Italy

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Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona

Ancona, , Italy

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Azienda Ospedaliera Policlinico di Bari

Bari, , Italy

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Policlinico Universitario di Catania

Catania, , Italy

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Istituto Clinico Humanitas Humanitas Cancer Center

Milan, , Italy

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Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

Milan, , Italy

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Presidio Ospedaliero di Pescara

Pescara, , Italy

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Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital

Nagoya, Aichi-ken, Japan

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Kyushu University Hospital

Fukuoka, Fukuoka, Japan

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Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital

Hiroshima, Hiroshima, Japan

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Hokkaido University Hospital

Sapporo, Hokkaido, Japan

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Okayama University Hospital

Okayama, Okayama-ken, Japan

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Shizuoka Cancer Center

Nakatogari, Shizuoka, Japan

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Jichi Medical University Hospital

Shimotsuke, Tochigi, Japan

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Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital

Bunkyo-Ku, Tokyo, Japan

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Osaka City University Hospital

Osaka, , Japan

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Hospital Universitario "Dr. Jose Eleuterio Gonzalez"

Monterrey, Nuevo León, Mexico

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Oslo University Hospital - Rikshospitalet

Oslo, , Norway

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Uniwersyteckie Centrum Kliniczne

Gdansk, Pomeranian Voivodeship, Poland

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Instituto Portugues de Oncologia de Lisboa Francisco Gentil

Lisbon, , Portugal

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Centro Hospitalar de Lisboa Norte EPE- Hospital Santa Maria

Lisbon, , Portugal

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Instituto Portugues de Oncologia do Porto Francisco Gentil

Porto, , Portugal

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Spitalul Clinic Judetean de Urgenta Targu Mure

Târgu Mureş, Mureș County, Romania

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Institutul Clinic Fundeni

Bucharest, , Romania

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Sverdlovsk Regional Clinical Hospital #1

Yekaterinburg, Sverdlovsk Oblast, Russia

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National Research Center for Hematology

Moscow, , Russia

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National University Hospital

Singapore, , Singapore

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Singapore General Hospital

Singapore, , Singapore

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Raffles Hospital

Singapore, , Singapore

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Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

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Seoul National University Hospital

Seoul, Gyeonggi-do, South Korea

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Kyungpook National University Hospital

Daegu, Gyeongsangbuk-do, South Korea

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Keimyung University Dongsan Hospital

Daegu, Gyeongsangbuk-do, South Korea

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Pusan National University Hospital

Pusan, Gyeongsangnam-do, South Korea

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Daegu Catholic University Medical Center

Daegu, , South Korea

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Chungnam National University Hospital

Daejeon, , South Korea

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Korea University Anam Hospital

Seoul, , South Korea

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Severance Hospital

Seoul, , South Korea

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Samsung Medical Center

Seoul, , South Korea

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The Catholic University of Korea - Seoul St. Mary's Hospital

Seoul, , South Korea

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Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, Spain

Site Status

Hospital Universitario de Gran Canaria Doctor Negrin

Las Palmas de Gran Canaria, LAS Palmas, Spain

Site Status

Clinica Universidad de Navarra

Pamplona, Navarre, Spain

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Hospital Universitario Ramon Y Cajal

Madrid, , Spain

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Hospital Universitario Fundacion Jimenez Diaz

Madrid, , Spain

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Hospital General Universitario Morales Meseguer

Murcia, , Spain

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Hospital Universitario Virgen de la Arrixaca

Murcia, , Spain

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Hospital Universitario de Salamanca

Salamanca, , Spain

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Hospital Universitario Virgen del Rocio

Seville, , Spain

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Hospital Clinico Universitario de Valencia

Valencia, , Spain

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Skanes Universitetssjukhus i Lund

Lund, Skåne County, Sweden

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Karolinska Universitetssjukhuset

Stockholm, , Sweden

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Universitatsspital Basel

Basel, , Switzerland

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Universitatsspital Zurich

Zurich, , Switzerland

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Buddhist Tzu Chi General Hospital

Hualien City, Hualien, Taiwan

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Kaohsiung Medical University Hospital

Kaohsiung City, , Taiwan

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China Medical University Hospital

Taichung, , Taiwan

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Taichung Veterans General Hospital

Taichung, , Taiwan

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National Taiwan University Hospital

Taipei, , Taiwan

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Koo Foundation Sun Yat-Sen Cancer Center

Taipei, , Taiwan

Site Status

Chang Gung Memorial Hospital

Taoyuan District, , Taiwan

Site Status

The Clatterbridge Cancer Centre NHS Foundation Trust

Liverpool, England, United Kingdom

Site Status

Barts Health NHS Trust

London, England, United Kingdom

Site Status

Imperial College Healthcare NHS Trust

London, England, United Kingdom

Site Status

Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, England, United Kingdom

Site Status

Cardiff and Vale University Health Board

Cardiff, Wales, United Kingdom

Site Status

Countries

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United States Argentina Australia Austria Belgium Brazil Canada France Germany Greece Hungary Israel Italy Japan Mexico Norway Poland Portugal Romania Russia Singapore South Korea Spain Sweden Switzerland Taiwan United Kingdom

References

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Chen YB, Mohty M, Zeiser R, Teshima T, Jamy O, Maertens J, Purtill D, Chen J, Cao H, Rossiter G, Jansson J, Floisand Y. Vedolizumab for the prevention of intestinal acute GVHD after allogeneic hematopoietic stem cell transplantation: a randomized phase 3 trial. Nat Med. 2024 Aug;30(8):2277-2287. doi: 10.1038/s41591-024-03016-4. Epub 2024 Jun 6.

Reference Type DERIVED
PMID: 38844797 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2018-002141-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

JapicCTI-184221

Identifier Type: REGISTRY

Identifier Source: secondary_id

U1111-1216-2319

Identifier Type: REGISTRY

Identifier Source: secondary_id

Vedolizumab-3035

Identifier Type: -

Identifier Source: org_study_id

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