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

• Sponsor: Millennium Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Takeda ( Millennium Pharmaceuticals, Inc. )

Study Description

Brief Summary:

The purpose of this study is to evaluate the efficacy and safety of vedolizumab in combination with background acute graft-versus-host disease (aGvHD) prophylaxis regimen compared to placebo and background aGvHD prophylaxis regimen on intestinal aGvHD-free survival in participants who receive allo-HSCT as treatment for a hematologic malignancy or myeloproliferative disorder.

Condition or disease	Intervention/treatment	Phase
Hematopoietic Stem Cells	Drug: Vedolizumab; Drug: Vedolizumab Placebo	Phase 3

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 patients. 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 patient 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 IV infusion)

This multi-center trial will be conducted worldwide. The overall time to participate in this study is 12 months.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 558 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• 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
• Actual Study Start Date: February 6, 2019
• Estimated Primary Completion Date: October 23, 2020
• Estimated Study Completion Date: April 23, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Vedolizumab 300 mg; Vedolizumab 300 mg, intravenous (IV) infusion, once on Days -1 (baseline), +13, +41, +69, +97, +125, and +153. Participants will receive background GvHD prophylaxis regimen.	Drug: Vedolizumab; Vedolizumab IV infusion; Other Name: MLN0002
Placebo Comparator: Placebo; Vedolizumab placebo-matching, IV infusion, once on Days -1 (baseline), +13, +41, +69, +97, +125, and +153. Participants will receive background GvHD prophylaxis regimen.	Drug: Vedolizumab Placebo; Vedolizumab placebo-matching IV infusion

Outcome Measures

Primary Outcome Measures :

1. Intestinal aGvHD-Free Survival by Day +180 After Allo-HSCT [ Time Frame: Baseline up to Day +180 ]
   Intestinal aGvHD-free survival is defined as the time from prophylaxis to first documentation of intestinal aGvHD clinical criteria or death, whichever occurs first by Day +180.

Secondary Outcome Measures :

1. Intestinal aGvHD-Free and Relapse-Free Survival by Day +180 [ Time Frame: Baseline up to Day +180 ]
   Intestinal aGvHD-free and relapse-free survival is defined as the time from prophylaxis to first documentation of intestinal aGvHD clinical criteria or death, whichever occurs first by Day +180.
2. Stage 2-4 aGvHD-Free Survival by Day +180 [ Time Frame: Baseline up to Day +180 ]
   Stage 2-4 aGvHD-free survival is defined as the time from prophylaxis to first documentation of stage 2-4 aGvHD clinical criteria or death, whichever occurs first by Day +180.
3. Nonrelapse Mortality (NRM) by Day +180 [ Time Frame: Baseline up to Day +180 ]
   Nonrelapse mortality is defined as death not attributable to disease recurrence.
4. Overall Survival (OS) by Day +180 [ Time Frame: Baseline up to Day +180 ]
   OS is defined as the time from the date of enrollment to the date of death, due to any cause.
5. Grade B-D aGvHD-Free Survival by Day +180 [ Time Frame: Baseline up to Day +180 ]
   Grade B-D aGvHD-free survival is defined as the time from prophylaxis to first documentation of Grade B-D aGvHD per international bone marrow transplant registry database (IBMTR) severity index.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Participants must undergo 8 of 8 or 7 of 8 human leukocyte antigen (HLA)-matched (antigen at HLA-A, -B, and -C, and allelic at HLA-DRB1) unrelated hematopoietic stem cell transplantation (HSCT) from either peripheral blood or bone marrow stem cells for a hematologic malignancy or myeloproliferative disorder.
2. Participants for whom a myeloablative conditioning or reduced intensity conditioning (RIC) is planned.
3. Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) eligible (meeting institutional criteria)-participants planned medical care should include acute graft-versus-host disease (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 graft-versus-host disease (GvHD) prophylaxis are excluded.
4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.

Exclusion Criteria:

1. Had prior allo- or autologous 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 (eg, aplastic anemia, sickle cell anemia, thalassemias, Fanconi anemia or immunodeficiency).

Contacts and Locations

Contacts

Contact: Takeda Study Registration Call Center; +1-877-825-3327; medicalinformation@tpna.com

Locations

Hungary

Debreceni Egyetem Klinikai Kozpont, Belgyogyaszati Klinika, Haematologiai Tanszek; Recruiting

Debrecen, Hajdu-bihar, Hungary, 4032

Sponsors and Collaborators

Millennium Pharmaceuticals, Inc.

Investigators

• Study Director: Medical Director Clinical Science; Takeda

More Information

• Responsible Party: Millennium Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT03657160 History of Changes
• Other Study ID Numbers: Vedolizumab-3035; 2018-002141-11 ( EudraCT Number ); JapicCTI-184221 ( Registry Identifier: JapicCTI )
• First Posted: September 3, 2018
• Last Update Posted: February 27, 2019
• Last Verified: February 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Takeda ( Millennium Pharmaceuticals, Inc. ):

Drug Therapy

Additional relevant MeSH terms:

Graft vs Host Disease; Immune System Diseases; Vedolizumab; Gastrointestinal Agents