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

Hematopoietic Stem Cells Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03657160
• Other study ID #: Vedolizumab-3035
• Secondary ID: 2018-002141-11Ja
• Status: Completed
• Phase: Phase 3
• Start date: February 6, 2019
• Est. completion date: May 9, 2022

Study information

• Verified date: May 2023
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 343
• Est. completion date: May 9, 2022
• Est. primary completion date: February 7, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Graft vs Host Disease
• Hematopoietic Stem Cells

Intervention

Drug:
• Vedolizumab Placebo
Vedolizumab placebo-matching IV infusion.
• Vedolizumab
Vedolizumab IV infusion.

Locations

Country	Name	City	State
Argentina	Fundacion Favaloro Hospital Universitario	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	Hospital Italiano de Buenos Aires	Ciudad Autonoma de Buenos Aires
Argentina	Hospital Privado Centro Medico de Cordoba	Cordoba
Australia	Saint Vincent's Hospital Sydney	Darlinghurst	New South Wales
Australia	Austin Health	Heidelberg	Victoria
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Fiona Stanley Hospital	Murdoch	Western Australia
Australia	The Royal Melbourne Hospital	Parkville	Victoria
Austria	Ordensklinikum Linz Elisabethinen	Linz	Upper Austria
Belgium	Ziekenhuisnetwerk Stuivenberg	Antwerpen
Belgium	Universitair Ziekenhuis Leuven	Leuven	Flemish Brabant
Brazil	Hospital de Cancer de Barretos	Barretos	SAO Paulo
Brazil	Instituto do Cancer e Transplante de Curitiba	Curitiba	Parana
Brazil	Hospital Universitario Walter Cantidio - Universidade Federal do Ceara	Fortaleza	Ceara
Brazil	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	Hospital Santa Marcelina	Sao Paulo
Brazil	Instituto Brasileiro de Controle do Cancer - Sao Camilo Oncolgia	Sao Paulo
Canada	Saskatchewan Cancer Agency	Saskatoon	Saskatchewan
Canada	CancerCare Manitoba	Winnipeg	Manitoba
France	Centre Hospitalier Universitaire Amiens-Picardie	Amiens	Picardie
France	Centre Hospitalier Universitaire de Limoges	Limoges Cedex	Limousin, Lorraine
France	Centre Hospitalier Universitaire Nantes - Hotel Dieu	Nantes Cedex 1	PAYS DE LA Loire
France	Groupe Hospitalier Pitie-Salpetriere	Paris	Ile-de-france
France	Hopital Necker-Enfants Malades	Paris	Ile-de-france
France	Hopital Saint-Antoine	Paris	Ile-de-france
France	Hopital Saint Louis	Paris Cedex 10	Ile-de-france
France	Hopital Pontchaillou	Rennes Cedex 9	Bretagne
Germany	Universitatsklinikum Carl Gustav Carus Dresden	Dresden	Sachsen
Germany	Universitatsklinikum Frankfurt	Frankfurt am Main	Hessen
Germany	Universitatsklinikum Halle	Halle	Sachsen-anhalt
Germany	Universitaetsklinikum Schleswig-Holstein - Campus Kiel	Kiel	Schleswig-holstein
Germany	Universitatsmedizin der Johannes Gutenberg Universitat Mainz	Mainz	Rheinland-pfalz
Germany	Universitatsmedizin Mannheim	Mannheim	Baden-wuerttemberg
Germany	Diakonie-Klinikum Stuttgart	Stuttgart	Baden-wuerttemberg
Greece	University General Hospital of Athens Attikon	Athens	Attica
Greece	University Regional General Hospital of Patras	Patras	Peloponnese
Hungary	Debreceni Egyetem Klinikai Kozpont	Debrecen	Hajdu-bihar
Israel	Soroka University Medical Center	Beer Sheva	Beersheba
Israel	Rambam Health Care Campus - Rambam Medical Center	Haifa
Israel	Hadassah Medical Center	Jerusalem
Israel	The Chaim Sheba Medical Center	Ramat Gan
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona	Ancona
Italy	Ospedale Mazzoni	Ascoli Piceno	Marche
Italy	Azienda Ospedaliera Policlinico di Bari	Bari
Italy	Policlinico Universitario di Catania	Catania
Italy	Ospedale dell'Angelo	Mestre	Venezia
Italy	Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda	Milano
Italy	Istituto Clinico Humanitas Humanitas Cancer Center	Milano
Italy	Presidio Ospedaliero di Pescara	Pescara
Italy	Azienda Grande Ospedale Metropolitano Bianchi Melacrino Morelli	Reggio Calabria	Calabria
Italy	Azienda Ospedaliera Cardinale G. Panico	Tricase	Lecce
Japan	Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital	Bunkyo-Ku	Tokyo
Japan	Kyushu University Hospital	Fukuoka-shi	Fukuoka
Japan	Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital	Hiroshima-shi	Hiroshima
Japan	Shizuoka Cancer Center	Nagaizumi	Shizuoka
Japan	Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital	Nagoya	Aichi
Japan	Okayama University Hospital	Okayama-city	Okayama
Japan	Osaka City University Hospital	Osaka
Japan	Hokkaido University Hospital	Sapporo-shi	Hokkaido
Japan	Jichi Medical University Hospital	Shimotsuke-city	Tochigi
Korea, Republic of	Pusan National University Hospital	Busan	Gyeongsangnam-do
Korea, Republic of	Daegu Catholic University Medical Center	Daegu
Korea, Republic of	Keimyung University Dongsan Hospital	Daegu	Gyeongsangbuk-do
Korea, Republic of	Kyungpook National University Hospital	Daegu	Gyeongsangbuk-do
Korea, Republic of	Chungnam National University Hospital	Daejeon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul	Gyeonggi-do
Korea, Republic of	Severance Hospital	Seoul
Korea, Republic of	The Catholic University of Korea - Seoul St. Mary's Hospital	Seoul
Mexico	Hospital Universitario "Dr. Jose Eleuterio Gonzalez"	Monterrey	Nuevo LEON
Norway	Oslo University Hospital - Rikshospitalet	Oslo
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk	Pomorskie
Portugal	Centro Hospitalar de Lisboa Norte EPE- Hospital Santa Maria	Lisboa
Portugal	Instituto Portugues de Oncologia de Lisboa Francisco Gentil	Lisboa
Portugal	Instituto Portugues de Oncologia do Porto Francisco Gentil	Porto
Romania	Institutul Clinic Fundeni	Bucuresti
Romania	Spitalul Clinic Judetean de Urgenta Targu Mure	Târgu-Mures	Mures
Russian Federation	Sverdlovsk Regional Clinical Hospital #1	Ekaterinburg	Sverdlovsk
Russian Federation	National Research Center for Hematology	Moscow
Singapore	National University Hospital	Singapore
Singapore	Raffles Hospital	Singapore
Singapore	Singapore General Hospital	Singapore
Spain	Hospital Universitari Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital Universitario de Gran Canaria Doctor Negrin	Las Palmas De Gran Canaria	LAS Palmas
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Hospital Universitario Ramon Y Cajal	Madrid
Spain	Hospital General Universitario Morales Meseguer	Murcia
Spain	Hospital Universitario Virgen de la Arrixaca	Murcia
Spain	Clinica Universidad de Navarra	Pamplona	Navarra
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Clinico Universitario de Valencia	Valencia
Sweden	Skanes Universitetssjukhus i Lund	Lund	Skane
Sweden	Karolinska Universitetssjukhuset	Stockholm
Switzerland	Universitatsspital Basel	Basel
Switzerland	Universitatsspital Zurich	Zurich
Taiwan	Buddhist Tzu Chi General Hospital	Hualien City	Hualien
Taiwan	Kaohsiung Medical University Hospital	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	Koo Foundation Sun Yat-Sen Cancer Center	Taipei
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Chang Gung Memorial Hospital	Taoyuan
United Kingdom	Cardiff and Vale University Health Board	Cardiff	Wales
United Kingdom	The Clatterbridge Cancer Centre NHS Foundation Trust	Liverpool	England
United Kingdom	Barts Health NHS Trust	London	England
United Kingdom	Imperial College Healthcare NHS Trust	London	England
United Kingdom	Sheffield Teaching Hospitals NHS Foundation Trust	Sheffield	England
United States	Children's Healthcare of Atlanta	Atlanta	Georgia
United States	Emory University - Winship Cancer Institute	Atlanta	Georgia
United States	Augusta University Georgia Cancer Center	Augusta	Georgia
United States	Marlene and Stewart Greenebaum Cancer Center	Baltimore	Maryland
United States	University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama
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	Massachusetts General Hospital	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Roswell Park Comprehensive Cancer Center	Buffalo	New York
United States	University of North Carolina Hospitals	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Robert H. Lurie Comprehensive Cancer Center of Northwestern University	Chicago	Illinois
United States	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	University of Kentucky Chandler Medical Center	Lexington	Kentucky
United States	David Geffen School of Medicine at University of California Los Angeles	Los Angeles	California
United States	Loyola University Medical Center	Maywood	Illinois
United States	Cohen Children's Medical Center	New Hyde Park	New York
United States	Columbia University Medical Center - The Columbia Center for Translational Immunology	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Oregon Health and Science University	Portland	Oregon
United States	Massey Cancer Center	Richmond	Virginia
United States	Mayo Clinic - Rochester	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Millennium Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Norway,  Poland,  Portugal,  Romania,  Russian Federation,  Singapore,  Spain,  Sweden,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Intestinal aGvHD-Free and Relapse-Free Survival	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.	From the date of first dose of study drug to first documented intestinal aGvHD, death or relapse, whichever occurs first up to Day +180
Secondary	Grade C-D aGvHD-Free Survival	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.	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
Secondary	Nonrelapse Mortality (NRM)	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.	From the date of first dose of study drug to first documented death without relapse, up to Day +180
Secondary	Overall Survival (OS)	Overall Survival by Days +180 is the time from the date of first study drug administration (Day-1) to death from any cause.	From the date of first dose of study drug to first documented death up to Day +180
Secondary	Grade B-D aGvHD-Free Survival	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.	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