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)

NCT02993783 | Terminated Phase 2 Results FDA Drug

• 3 other identifiers: Vedolizumab-20042016-002985-30U1111-1185-6832
• Study Type: interventional
• Target: 17
• Locations: 5 countries
• Sites: 15

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.

Conditions

Allogeneic Hematopoietic Stem Cell Transplantation

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Overall Response (Partial Response [PR]+Very Good Partial Response [VGPR]+Complete Response [CR]) at Day 28

  CR is defined as the resolution of all signs and symptoms of acute graft-versus-host-disease (GvHD). VGPR is defined as resolution of the signs and symptoms of the GvHD: 1) Skin: no rash, or residual erythematous rash involving \<25% of the body surface, without bullae (excluding residual faint erythema and hyperpigmentation). 2) Liver: total serum bilirubin concentration \<2 mg/dL or \<25% of baseline at enrollment. 3) Gut: a) participant tolerates food or enteral feeding; b) predominantly formed stools; c) no overt gastrointestinal bleeding or abdominal cramping; d) no more than occasional nausea or vomiting. PR is defined as improvement of 1 GvHD stage in 1 or more organs without progression in any organ.

  Day 28

• Number of Participants Who Experienced Serious Adverse Events (SAEs) Through Day 28

  An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An SAE is defined as an untoward medical occurrence, significant hazard, contraindication, side effect or precaution that at any dose: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

  From first dose up to Day 28

Secondary Outcomes (11)

• Percentage of Participants Who Died in the Absence of Primary Malignancy Relapse After Allo-HSCT at Month 6

  Month 6

• Percentage of Participants With Acute GvHD Complete Response (CR) at Day 28

  Day 28

• Percentage of Participants With Intestinal Overall Response at Day 28

  Day 28

• Kaplan-Meier Estimate of Percentage of Participants Achieving Survival at Months 6 and 12

  Months 6 and 12

• Percentage of Participants Alive Without GvHD or Primary Malignancy Relapse at Months 6 and 12

  Months 6 and 12

Study Arms (2)

Vedolizumab 300 mg

EXPERIMENTAL

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

Drug: Vedolizumab

Vedolizumab 600 mg

EXPERIMENTAL

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

Drug: Vedolizumab

Interventions

Vedolizumab DRUG

Vedolizumab IV infusion

Also known as: Entyvio, MLN0002

Vedolizumab 300 mg; Vedolizumab 600 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Recipient of 1 allogeneic hematopoietic stem cell transplantation (allo-HSCT) but not more than 1 allo-HSCT.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 3.
• Evidence of myeloid engraftment defined by absolute neutrophil count greater than or equal to (\>=) 0.5\*109/liter (L) on 3 consecutive days.

You may not qualify if:

• Presence of chronic GvHD at Screening (including acute-chronic overlap syndrome).
• Relapse of underlying malignant disease after allo-HSCT.
• Hyperacute GvHD defined as onset of GvHD within the first 15 days following hematopoietic stem cell infusion.
• Received systemic agents other than corticosteroids for treatment of acute GvHD. GvHD prophylaxis agents (example, calcineurin inhibitors) may be continued.
• Life expectancy of \<3 weeks.

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (15)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Mount Sinai - PRIME

Lake Success, New York, 11041, United States

Location

OSU - James Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Baylor University Medical Center

Dallas, Texas, 75204, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

ZNA Stuivenberg

Antwerp, 2060, Belgium

Location

AZ Sint-Jan Brugge

Bruges, 8000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

CHU Nantes - Hotel Dieu

Nantes, Loire Atlantique, 44093, France

Location

Hopital Claude Huriez - CHU Lille

Lille, Nord, 59037, France

Location

Hopital Saint-Antoine

Paris, Paris, 75571, France

Location

Oslo Universitetssykehus - Rikshospitalet

Oslo, 3072, Norway

Location

Skanes Universitetssjukhus, Lund

Lund, 22185, Sweden

Location

Akademiska Sjukhuset

Uppsala, 75185, Sweden

Location

Related Publications (1)

• 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.

  PMID: 34108672 DERIVED

MeSH Terms

Interventions

vedolizumab

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Millennium Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2016
• First Posted: December 15, 2016
• Study Start: April 28, 2017
• Primary Completion: May 9, 2018
• Study Completion: May 9, 2018
• Last Updated: May 24, 2019
• Results First Posted: May 24, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will share

Locations

NO (1); US (6); BE (3); SE (2); FR (3)