Clinical trial NCT03657160: Vedolizumab in the Prophylaxis of Intestinal Acute Graft Versus Host Disease (aGVHD) in Participants Undergoing Allogeneic Hematopoietic Stem Cell (Allo-HSCT) Transplantation
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hematopoietic Stem Cells
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2018-09-04
Enrollment: 343
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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 \<= 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).

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