Clinical trial NCT02993783: 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)
Official title: An Open-Label, Dose-Finding Study of Vedolizumab IV for Treatment of Steroid-Refractory Acute Intestinal Graft-Versus-Host Disease (GvHD) in Patients Who Have Undergone Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Allogeneic Hematopoietic Stem Cell Transplantation
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2016-12-15
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Percentage of Participants With Overall Response (Partial Response [PR]+Very Good Partial Response [VGPR]+Complete Response [CR]) at Day 28
timeFrame: Day 28
measure: Number of Participants Who Experienced Serious Adverse Events (SAEs) Through Day 28
timeFrame: From first dose up to Day 28
Secondary outcomes:
measure: Percentage of Participants Who Died in the Absence of Primary Malignancy Relapse After Allo-HSCT at Month 6
timeFrame: Month 6
measure: Percentage of Participants With Acute GvHD Complete Response (CR) at Day 28
timeFrame: Day 28
measure: Percentage of Participants With Intestinal Overall Response at Day 28
timeFrame: Day 28
measure: Kaplan-Meier Estimate of Percentage of Participants Achieving Survival at Months 6 and 12
timeFrame: Months 6 and 12
measure: Percentage of Participants Alive Without GvHD or Primary Malignancy Relapse at Months 6 and 12
timeFrame: Months 6 and 12
measure: Total Dose of Steroids Administered
timeFrame: From first dose of study drug up to Months 6 and 12
measure: Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs)
timeFrame: From first dose of study drug to 18 weeks after last dose (Up to Week 32)
measure: Number of Participants Who Experienced Serious Adverse Events (SAEs) Through Week 32
timeFrame: From first dose of study drug to 18 weeks after last dose (Up to Week 32)
measure: Number of Participants With Markedly Abnormal Laboratory Parameters Values
timeFrame: From Baseline up to last dose of study drug (Day 99)
measure: Number of Participants With Markedly Abnormal Vital Signs
timeFrame: From Baseline up to last dose of study drug (Day 99)
measure: Ctrough: Trough Serum Concentrations of Vedolizumab
timeFrame: Day 99 (pre-dose)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Lake Success
country: United States
facility: Mount Sinai - PRIME
state: New York
city: Columbus
country: United States
facility: OSU - James Comprehensive Cancer Center
state: Ohio
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Antwerpen
country: Belgium
facility: ZNA Stuivenberg
city: Brugge
country: Belgium
facility: AZ Sint-Jan Brugge
city: Leuven
country: Belgium
facility: UZ Leuven
city: Nantes cedex 1
country: France
facility: CHU Nantes - Hotel Dieu
state: Loire Atlantique
city: Lille cedex
country: France
facility: Hopital Claude Huriez - CHU Lille
state: Nord
city: Paris cedex 12
country: France
facility: Hopital Saint-Antoine
state: Paris
city: Oslo
country: Norway
facility: Oslo Universitetssykehus - Rikshospitalet
city: Lund
country: Sweden
facility: Skanes Universitetssjukhus, Lund
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Study Director
role: STUDY_DIRECTOR
References:
citation: 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.