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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03657160
Recruitment Status : Recruiting
First Posted : September 4, 2018
Last Update Posted : July 21, 2020
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Tracking Information
First Submitted Date  ICMJE August 30, 2018
First Posted Date  ICMJE September 4, 2018
Last Update Posted Date July 21, 2020
Actual Study Start Date  ICMJE February 6, 2019
Estimated Primary Completion Date October 23, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 4, 2019)
Intestinal aGvHD-Free Survival by Day +180 After Allo-HSCT [ Time Frame: From the date of first dose of study drug to first documented intestinal aGvHD or death, whichever occurs first (up to Day +180) ]
Intestinal aGvHD-free survival is defined as the time from the date of first dose of study drug to first documented intestinal aGvHD per aGVHD Clinical Stage criteria or death due to any cause, whichever occurs first.
Original Primary Outcome Measures  ICMJE
 (submitted: August 30, 2018)
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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 4, 2019)
  • Intestinal aGvHD-Free and Relapse-Free Survival by Day +180 [ Time Frame: From the date of first dose of study drug to first documented intestinal aGvHD criteria, relapse or death, whichever occurs first (up to Day +180) ]
    Intestinal aGvHD-free and relapse-free survival is defined as the time from the date of first dose of study drug to first documented intestinal aGvHD per aGVHD Clinical Stage criteria, relapse or death due to any cause, whichever occurs first.
  • Grade C-D aGvHD-Free Survival by Day +180 [ Time Frame: 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 defined as the time from the date of first dose of study drug to first documented Grade C-D aGvHD per international bone marrow transplant registry database (IBMTR) severity index or death due to any cause, whichever occurs first.
  • Nonrelapse Mortality (NRM) by Day +180 [ Time Frame: From the date of first dose of study drug to the date of death without occurrence of a relapse (up to Day +180) ]
    NRM is defined as death not attributable to disease recurrence and will be assessed from the date of first dose of study drug to the date of death without occurrence of a relapse.
  • Overall Survival (OS) by Day +180 [ Time Frame: From the date of the date of first dose of study drug to the date of death (up to Day +180) ]
    OS is defined as the time from the date of the date of first dose of study drug to the date of death, due to any cause.
  • Grade B-D aGvHD-Free Survival by Day +180 [ Time Frame: From the date of first dose of study drug to first documented Grade B-D or death, whichever occurs first (up to Day +180) ]
    Grade B-D aGvHD-free survival is defined as the time from the date of first dose of study drug to first documented Grade B-D aGvHD per IBMTR severity index or death due to any cause, whichever occurs first.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 30, 2018)
  • 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.
  • 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.
  • Nonrelapse Mortality (NRM) by Day +180 [ Time Frame: Baseline up to Day +180 ]
    Nonrelapse mortality is defined as death not attributable to disease recurrence.
  • 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.
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Vedolizumab in the Prophylaxis of Intestinal Acute Graft Versus Host Disease (aGVHD) in Participants Undergoing Allogeneic Hematopoietic Stem Cell (Allo-HSCT) Transplantation
Official Title  ICMJE 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
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Hematopoietic Stem Cells
Intervention  ICMJE
  • Drug: Vedolizumab
    Vedolizumab intravenous infusion.
    Other Name: MLN0002
  • Drug: Vedolizumab Placebo
    Vedolizumab placebo-matching intravenous infusion.
Study Arms  ICMJE
  • Experimental: Vedolizumab 300 mg
    Vedolizumab 300 milligram (mg), intravenous infusion, once on Days -1 (baseline), +13, +41, +69, +97, +125, and +153. Participants will receive background graft-versus-host disease (GvHD) prophylaxis regimen.
    Intervention: Drug: Vedolizumab
  • Placebo Comparator: Placebo
    Vedolizumab placebo-matching, intravenous infusion, once on Days -1 (baseline), +13, +41, +69, +97, +125, and +153. Participants will receive background GvHD prophylaxis regimen.
    Intervention: Drug: Vedolizumab Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 30, 2018)
558
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 23, 2021
Estimated Primary Completion Date October 23, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Must be greater than or equal to (>=) 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 less than or equal to (<=) 2 for participants aged >=18 years at randomization or >=60 percent (%) using the Karnofsky performance status for adolescent subjects aged >=16 years at randomization or the Lansky performance status for adolescent participants aged 12 to less than (<) 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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Takeda Study Registration Call Center +1-877-825-3327 medinfoUS@takeda.com
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   Brazil,   Canada,   France,   Germany,   Greece,   Hungary,   Israel,   Italy,   Japan,   Korea, Republic of,   Norway,   Poland,   Portugal,   Romania,   Russian Federation,   Singapore,   Spain,   Sweden,   Switzerland,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03657160
Other Study ID Numbers  ICMJE Vedolizumab-3035
2018-002141-11 ( EudraCT Number )
JapicCTI-184221 ( Registry Identifier: JapicCTI )
U1111-1216-2319 ( Registry Identifier: WHO )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com 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.
Responsible Party Takeda ( Millennium Pharmaceuticals, Inc. )
Study Sponsor  ICMJE Millennium Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Clinical Science Takeda
PRS Account Takeda
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP