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

NCT03657160 | Completed Phase 3 Results DMC FDA Drug

• 4 other identifiers: Vedolizumab-30352018-002141-11JapicCTI-184221U1111-1216-2319
• Study Type: interventional
• Target: 343
• Locations: 26 countries
• Sites: 138

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.

Conditions

Hematopoietic Stem Cells

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (1)

• Intestinal aGvHD-Free Survival After Allo-HSCT by +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.

  From the date of first dose of study drug to first documented intestinal aGvHD or death, whichever occurs first up to +180 days

Secondary Outcomes (5)

• 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

• 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

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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).

Drug: Vedolizumab Placebo

Vedolizumab 300 mg

EXPERIMENTAL

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).

Drug: Vedolizumab

Interventions

Vedolizumab Placebo DRUG

Vedolizumab placebo-matching IV infusion.

Placebo

Vedolizumab DRUG

Vedolizumab IV infusion.

Also known as: MLN0002

Vedolizumab 300 mg

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (139)

University of Alabama at Birmingham Comprehensive Cancer Center

Birmingham, Alabama, 35294, United States

Location

David Geffen School of Medicine at University of California Los Angeles

Los Angeles, California, 90095, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Emory University - Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Augusta University Georgia Cancer Center

Augusta, Georgia, 30912, United States

Location

Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Chicago, Illinois, 60611, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

University of Kentucky Chandler Medical Center

Lexington, Kentucky, 40536, United States

Location

Marlene and Stewart Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

Location

Cohen Children's Medical Center

New Hyde Park, New York, 11040, United States

Location

Weill Cornell Medical College

New York, New York, 10021, United States

Location

Columbia University Medical Center - The Columbia Center for Translational Immunology

New York, New York, 10032, United States

Location

University of North Carolina Hospitals

Chapel Hill, North Carolina, 27514, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

Fundacion Favaloro Hospital Universitario

Ciudad Autonoma de Buenos Aires, Buenos Aires, C1093AAS, Argentina

Location

Hospital Italiano de Buenos Aires

Buenos Aires, C1199ABB, Argentina

Location

Hospital Privado Centro Medico de Cordoba

Córdoba, X5014KEH, Argentina

Location

Saint Vincent's Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

Location

Royal Brisbane and Women's Hospital

Herston, Queensland, 4006, Australia

Location

Austin Health

Heidelberg, Victoria, 3084, Australia

Location

The Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Fiona Stanley Hospital

Murdoch, Western Australia, 6150, Australia

Location

Ordensklinikum Linz Elisabethinen

Linz, Upper Austria, 4020, Austria

Location

Universitair Ziekenhuis Leuven

Leuven, Flemish Brabant, 3000, Belgium

Location

Ziekenhuisnetwerk Stuivenberg

Antwerp, 2060, Belgium

Location

Hospital Universitario Walter Cantidio - Universidade Federal do Ceara

Fortaleza, Ceará, 60430-380, Brazil

Location

Instituto do Cancer e Transplante de Curitiba

Curitiba, Paraná, 80510-130, Brazil

Location

Hospital de Cancer de Barretos

Barretos, São Paulo, 14784-400, Brazil

Location

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

São Paulo, 01246-000, Brazil

Location

Fundacao Antonio Prudente - A.C.Camargo Cancer Center

São Paulo, 01509-010, Brazil

Location

Instituto Brasileiro de Controle do Cancer - Sao Camilo Oncolgia

São Paulo, 03102-006, Brazil

Location

Hospital Santa Marcelina

São Paulo, 08270-070, Brazil

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Saskatchewan Cancer Agency

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Hopital Pontchaillou

Rennes, Brittany Region, 35033, France

Location

Centre Hospitalier Universitaire de Limoges

Limoges, Limousin, Lorraine, 87042, France

Location

Centre Hospitalier Universitaire Nantes - Hotel Dieu

Nantes, Pays de la Loire Region, 44093, France

Location

Centre Hospitalier Universitaire Amiens-Picardie

Amiens, Picardie, 80054 CEDEX 1, France

Location

Hopital Saint-Antoine

Paris, Île-de-France Region, 75012, France

Location

Groupe Hospitalier Pitie-Salpetriere

Paris, Île-de-France Region, 75013, France

Location

Hopital Necker-Enfants Malades

Paris, Île-de-France Region, 75473 cedex 15, France

Location

Hopital Saint Louis

Paris, Île-de-France Region, 75475, France

Location

Universitatsmedizin Mannheim

Mannheim, Baden-Wurttemberg, 68167, Germany

Location

Diakonie-Klinikum Stuttgart

Stuttgart, Baden-Wurttemberg, 70176, Germany

Location

Universitatsklinikum Frankfurt

Frankfurt am Main, Hesse, 60590, Germany

Location

Universitatsmedizin der Johannes Gutenberg Universitat Mainz

Mainz, Rhineland-Palatinate, 55131, Germany

Location

Universitatsklinikum Carl Gustav Carus Dresden

Dresden, Saxony, 01307, Germany

Location

Universitatsklinikum Halle

Halle, Saxony-Anhalt, 06120, Germany

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Universitaetsklinikum Schleswig-Holstein - Campus Kiel

Kiel, Schleswig-Holstein, 24105, Germany

Location

University General Hospital of Athens Attikon

Athens, Attica, 12462, Greece

Location

University Regional General Hospital of Patras

Patras, Peloponnese, 26504, Greece

Location

Debreceni Egyetem Klinikai Kozpont

Debrecen, Hajdú-Bihar, 4032, Hungary

Location

Soroka University Medical Center

Beersheba, Beersheba, 84101, Israel

Location

Rambam Health Care Campus - Rambam Medical Center

Haifa, 3109601, Israel

Location

Hadassah Medical Center

Jerusalem, 9112001, Israel

Location

The Chaim Sheba Medical Center

Ramat Gan, 5265601, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 6423906, Israel

Location

Azienda Grande Ospedale Metropolitano Bianchi Melacrino Morelli

Reggio Calabria, Calabria, 89122, Italy

Location

Azienda Ospedaliera Cardinale G. Panico

Tricase, Lecce, 73039, Italy

Location

Ospedale Mazzoni

Ascoli Piceno, The Marches, 63100, Italy

Location

Ospedale dell'Angelo

Mestre, Venezia, 30174, Italy

Location

Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona

Ancona, 60126, Italy

Location

Azienda Ospedaliera Policlinico di Bari

Bari, 70124, Italy

Location

Policlinico Universitario di Catania

Catania, 95124, Italy

Location

Istituto Clinico Humanitas Humanitas Cancer Center

Milan, 20089', Italy

Location

Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

Presidio Ospedaliero di Pescara

Pescara, 65125, Italy

Location

Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital

Nagoya, Aichi-ken, 453-8511, Japan

Location

Kyushu University Hospital

Fukuoka, Fukuoka, 812-8582, Japan

Location

Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital

Hiroshima, Hiroshima, 730-8619, Japan

Location

Hokkaido University Hospital

Sapporo, Hokkaido, 060-8648, Japan

Location

Okayama University Hospital

Okayama, Okayama-ken, 700-8558, Japan

Location

Shizuoka Cancer Center

Nakatogari, Shizuoka, 411-8777, Japan

Location

Jichi Medical University Hospital

Shimotsuke, Tochigi, 329-0498, Japan

Location

Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital

Bunkyo-Ku, Tokyo, 113-8677, Japan

Location

Osaka City University Hospital

Osaka, 545-8586, Japan

Location

Hospital Universitario "Dr. Jose Eleuterio Gonzalez"

Monterrey, Nuevo León, 64460, Mexico

Location

Oslo University Hospital - Rikshospitalet

Oslo, 0372, Norway

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, Pomeranian Voivodeship, 80-214, Poland

Location

Instituto Portugues de Oncologia de Lisboa Francisco Gentil

Lisbon, 1099-023, Portugal

Location

Centro Hospitalar de Lisboa Norte EPE- Hospital Santa Maria

Lisbon, 1649-035, Portugal

Location

Instituto Portugues de Oncologia do Porto Francisco Gentil

Porto, 4200-072, Portugal

Location

Spitalul Clinic Judetean de Urgenta Targu Mure

Târgu Mureş, Mureș County, 540042, Romania

Location

Institutul Clinic Fundeni

Bucharest, 022328, Romania

Location

Sverdlovsk Regional Clinical Hospital #1

Yekaterinburg, Sverdlovsk Oblast, 620102, Russia

Location

National Research Center for Hematology

Moscow, 125167, Russia

Location

National University Hospital

Singapore, 119228, Singapore

Location

Singapore General Hospital

Singapore, 169608, Singapore

Location

Raffles Hospital

Singapore, 188770, Singapore

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

Seoul National University Hospital

Seoul, Gyeonggi-do, 03080, South Korea

Location

Kyungpook National University Hospital

Daegu, Gyeongsangbuk-do, 41944, South Korea

Location

Keimyung University Dongsan Hospital

Daegu, Gyeongsangbuk-do, 42601, South Korea

Location

Pusan National University Hospital

Pusan, Gyeongsangnam-do, 49241, South Korea

Location

Daegu Catholic University Medical Center

Daegu, 42472, South Korea

Location

Chungnam National University Hospital

Daejeon, 35015, South Korea

Location

Korea University Anam Hospital

Seoul, 02841, South Korea

Location

Severance Hospital

Seoul, 03722, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

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

Seoul, 06591, South Korea

Location

Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Hospital Universitario de Gran Canaria Doctor Negrin

Las Palmas de Gran Canaria, LAS Palmas, 35010, Spain

Location

Clinica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital Universitario Ramon Y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital General Universitario Morales Meseguer

Murcia, 30008, Spain

Location

Hospital Universitario Virgen de la Arrixaca

Murcia, 30120, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Skanes Universitetssjukhus i Lund

Lund, Skåne County, 221 85, Sweden

Location

Karolinska Universitetssjukhuset

Stockholm, 141 86, Sweden

Location

Universitatsspital Basel

Basel, 4031, Switzerland

Location

Universitatsspital Zurich

Zurich, 8091, Switzerland

Location

Buddhist Tzu Chi General Hospital

Hualien City, Hualien, 970, Taiwan

Location

Kaohsiung Medical University Hospital

Kaohsiung City, 807, Taiwan

Location

China Medical University Hospital

Taichung, 404, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Koo Foundation Sun Yat-Sen Cancer Center

Taipei, 11259, Taiwan

Location

Chang Gung Memorial Hospital

Taoyuan District, 333, Taiwan

Location

The Clatterbridge Cancer Centre NHS Foundation Trust

Liverpool, England, L7 8XP, United Kingdom

Location

Barts Health NHS Trust

London, England, EC1M 6BQ, United Kingdom

Location

Imperial College Healthcare NHS Trust

London, England, W12 0HS, United Kingdom

Location

Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, England, S10 2JF, United Kingdom

Location

Cardiff and Vale University Health Board

Cardiff, Wales, CF14 4XW, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 38844797 DERIVED

MeSH Terms

Interventions

vedolizumab

Results Point of Contact

• Title: Study Director
• Organization: Takeda

medinfoUS@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2018
• First Posted: September 4, 2018
• Study Start: February 6, 2019
• Primary Completion: February 7, 2022
• Study Completion: May 9, 2022
• Last Updated: June 6, 2023
• Results First Posted: April 14, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

FR (8); GR (2); US (27); IT (10); AU (5); JP (9); TW (7); NO (1); PL (1); PT (3); ES (10); GB (5); BE (2); SE (2); AR (3); BR (7); HU (1); RU (2); DE (7); SG (3); CH (2); IL (5); ME (1); CA (2); KR (11); RO (2)