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

Phase 3

Completed

• Conditions: Hematopoietic Stem Cells
• Interventions: Drug: Vedolizumab Placebo; Drug: Vedolizumab

• 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.

Study Timeline

• Study First Submitted: 2018-08-30
• Study First Submitted QC: 2018-08-30
• Study First Posted: 2018-09-04
• Study Start: 2019-02-06
• Primary Completion: 2022-02-07
• Study Completion: 2022-05-09
• Results First Submitted: 2023-02-07
• Results First Submitted QC: 2023-03-22
• Results First Posted: 2023-04-14
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-09
• Last Update Posted: 2023-06-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 343

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).

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)

University of Alabama at Birmingham Comprehensive Cancer Center; 🇺🇸 Birmingham, Alabama, United States

David Geffen School of Medicine at University of California Los Angeles; 🇺🇸 Los Angeles, California, 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

Robert H. Lurie Comprehensive Cancer Center of Northwestern University; 🇺🇸 Chicago, Illinois, United States

Loyola University Medical Center; 🇺🇸 Maywood, Illinois, United States

Indiana University Melvin and Bren Simon Cancer Center; 🇺🇸 Indianapolis, Indiana, United States

University of Kentucky Chandler Medical Center; 🇺🇸 Lexington, Kentucky, United States

Marlene and Stewart Greenebaum Cancer Center; 🇺🇸 Baltimore, Maryland, United States

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