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)

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 will enroll approximately 38 participants. Participants will be randomly assigned
(by chance, like flipping a coin) to one of the two treatment groups:

- Vedolizumab IV 300 mg

- Vedolizumab IV 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. The cohort at the chosen dose level will then be expanded by
approximately 18 additional evaluable participants to further assess the tolerability and
effectiveness of vedolizumab. Both dose levels may be expanded based on accumulating results,
if necessary.

This multi-center trial will be conducted in multiple countries. The overall time to
participate in this study is 36 months. Participants will make multiple visits to the clinic
after last dose of study drug for a follow-up assessment.

Inclusion Criteria:

1. Recipient of 1 allo-HSCT but not more than 1 allo-HSCT.

2. Has primary steroid-refractory 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.