A Dose-Finding Study of Vedolizumab for Treatment of Steroid-Refractory Acute Intestinal Graft-Versus-Host Disease (GvHD) in Participants Who Have Undergone Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT)

NCT ID: NCT02993783

Last Updated: 2019-05-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-28
• Study Completion Date: 2018-05-09

Brief Summary

The purpose of this study is to assess the initial activity, tolerability, safety and to identify a recommended dose and regimen of vedolizumab intravenous (IV) administered for treatment of steroid-refractory acute intestinal GvHD in participants who have undergone allo-HSCT.

Detailed Description

The drug being tested in this study is called vedolizumab. This study will look at the tolerability and effectiveness of vedolizumab IV in participants with acute intestinal GvHD who have received no systemic therapy for the treatment of acute GvHD (prophylaxis acceptable) other than corticosteroids.

The study enrolled 17 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups:

• Vedolizumab 300 mg
• Vedolizumab 600 mg

All participants will be infused intravenously at the same time each day throughout the study. Vedolizumab IV will be administered on Days 1, 15, 43, 71, and 99. After approximately 10 participants are enrolled at each dose level and have data available from the Day 28 evaluation, safety, tolerability, efficacy, and pharmacokinetic (PK), results will be assessed for each dose level, and the appropriate dose for subsequent participants in the study will be determined.

This multi-center trial will be conducted in multiple countries. The overall time to participate in this study is 32 weeks. Participants will make multiple visits to the clinic after last dose of study drug for a follow-up assessment.

Conditions

Allogeneic Hematopoietic Stem Cell Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Vedolizumab 300 mg

Vedolizumab 300 mg, intravenous (IV) infusion, once on Days 1, 15, 43, 71 and 99.

Group Type: EXPERIMENTAL

Vedolizumab

Intervention Type: DRUG

Vedolizumab IV infusion

Vedolizumab 600 mg

Vedolizumab 600 mg, IV infusion, once on Days 1, 15, 43, 71 and 99.

Group Type: EXPERIMENTAL

Vedolizumab

Intervention Type: DRUG

Vedolizumab IV infusion

Interventions

Vedolizumab

Vedolizumab IV infusion

Intervention Type: DRUG

Other Intervention Names

Entyvio; MLN0002

Eligibility Criteria

Inclusion Criteria

1. Recipient of 1 allogeneic hematopoietic stem cell transplantation (allo-HSCT) but not more than 1 allo-HSCT.

2. Has primary steroid-refractory graft-versus-host disease (GvHD). Steroid-refractory disease is defined as worsening or no improvement in 5 to 7 days of treatment with methylprednisolone 2 milligram per kilogram (mg/kg) or equivalent or lack of a CR after 14 days of primary treatment with methylprednisolone 2 mg/kg or equivalent. Note that participants who develop intestinal GvHD while receiving systemic therapy for other GvHD are still eligible after 5 to 7 days, even if the intestinal GvHD has not been present for the entire duration. Participants who may have received an increase in their steroid dose treatment (example, increased methylprednisolone from 1 mg/kg to 2 mg/kg) before enrollment will be eligible, provided the participant has met the definition of steroid refractory above. Participants who develop toxicity on corticosteroids or who are otherwise medically unable to be dosed to this level, will also be eligible.

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 3.

4. Evidence of myeloid engraftment defined by absolute neutrophil count greater than or equal to (>=) 0.5*109/liter (L) on 3 consecutive days.

Exclusion Criteria

1. Presence of chronic GvHD at Screening (including acute-chronic overlap syndrome).

2. Relapse of underlying malignant disease after allo-HSCT.

3. Hyperacute GvHD defined as onset of GvHD within the first 15 days following hematopoietic stem cell infusion.

4. Received systemic agents other than corticosteroids for treatment of acute GvHD. GvHD prophylaxis agents (example, calcineurin inhibitors) may be continued.

5. Life expectancy of <3 weeks.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Millennium Pharmaceuticals, Inc.

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Washington University

St Louis, Missouri, United States

Mount Sinai - PRIME

Lake Success, New York, United States

OSU - James Comprehensive Cancer Center

Columbus, Ohio, United States

Baylor University Medical Center

Dallas, Texas, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

ZNA Stuivenberg

Antwerp, , Belgium

AZ Sint-Jan Brugge

Bruges, , Belgium

UZ Leuven

Leuven, , Belgium

CHU Nantes - Hotel Dieu

Nantes, Loire Atlantique, France

Hopital Claude Huriez - CHU Lille

Lille, Nord, France

Hopital Saint-Antoine

Paris, Paris, France

Oslo Universitetssykehus - Rikshospitalet

Oslo, , Norway

Skanes Universitetssjukhus, Lund

Lund, , Sweden

Akademiska Sjukhuset

Uppsala, , Sweden

Countries

United States; Belgium; France; Norway; Sweden

References

Floisand Y, Schroeder MA, Chevallier P, Selleslag D, Devine S, Renteria AS, Mohty M, Yakoub-Agha I, Chen C, Parfionovas A, Quadri S, Jansson J, Akbari M, Chen YB. A phase 2a randomized clinical trial of intravenous vedolizumab for the treatment of steroid-refractory intestinal acute graft-versus-host disease. Bone Marrow Transplant. 2021 Oct;56(10):2477-2488. doi: 10.1038/s41409-021-01356-0. Epub 2021 Jun 9.

Reference Type: DERIVED

PMID: 34108672 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

2016-002985-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1185-6832

Identifier Type: OTHER

Identifier Source: secondary_id

Vedolizumab-2004

Identifier Type: -

Identifier Source: org_study_id