Dose Finding Study of Vedolizumab for Graft-Versus-Host Disease (GvHD) in Participants Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

The drug being tested in this study is called Vedolizumab. Vedolizumab (also called MLN0002)
is approved for the treatment of adult participants with moderately to severely active UC and
CD who achieved an inadequate response, had a loss of response, or were intolerant to
conventional and/or biologic treatments. This study will look at the tolerability and
pharmacokinetics of Vedolizumab in participants undergoing allo-HSCT when added to standard
GvHD prophylaxis (tacrolimus plus short-term methotrexate) for the prevention of acute GvHD
(major complication in allo-HSCT).

The study will enroll approximately 36 participants. Participants will be assigned to
different dose-escalating cohorts in order to find out the recommended phase 2 dose (RP2D) of
the study:

- Cohort 1: Vedolizumab 75 mg

- Cohort 2: Vedolizumab 300 mg

- Cohort 3: Vedolizumab Dose 1

All participants have to receive 1 injection of Vedolizumab on Day -1 before allo-HSCT and on
Days 13 and 42 after allo-HSCT. If none of the participants receiving vedolizumab at 75 mg
experience dose-limiting toxicities (DLTs), dose escalation will continue to 300 mg on Day -1
before allo-HSCT and on Days +13 and +42 after allo-HSCT. If the first 3 participants at 300
mg tolerate the treatment without experiencing DLTs, then the decision on whether to increase
the vedolizumab IV dose in the next cohort will be guided by the PK results.

Cohorts will be escalated in same manner until the identification of RP2D. The cohort at that
dose level may be expanded to include approximately 18 additional participants undergoing
myeloablative conditioning or reduced-intensity conditioning (RIC) and receiving either
related or unrelated allo-HSCT for the treatment of hematologic malignancies or
myeloproliferative neoplasms. This group of participants will allow the further assessment of
the tolerability and clinical activity of vedolizumab.

This multi-center trial will be conducted in the United States. The overall time to
participate in this study will be approximately 2 years. Following the treatment period,
participants who remain in remission will be followed for development of acute and chronic
GvHD and safety during clinic visits at 4, 5, 6, 9, and 12 months after allo-HSCT or until
death or withdrawal of consent or termination of the study by the sponsor. Participants who
complete the study will attend a 12-month follow-up visit. Patients who have been
discontinued from treatment will attend an end of treatment visit 30 to 40 days after the
last dose of study drug using all study procedures outlined for the 12-month follow-up visit.

Inclusion Criteria:

1. Is undergoing matched or single-antigen mismatched unrelated-donor myeloablative
transplant for the treatment of ALL or AML; Is less than or equal to (<=) 60 years of
age For the cohort after Recommended phase 2 dose (RP2D)

2. Is undergoing matched or single-antigen mismatched related or unrelated-donor
transplant and receiving myeloablative conditioning or RIC for the treatment of
hematologic malignancies or myeloproliferative neoplasms; Is less than or equal to
(<=) 75 years of age

Exclusion Criteria:

1. Has received prior allogeneic transplants or who are planned to undergo umbilical cord
blood transplant, receive ex vivo T-cell-depleted hematopoietic stem cells (HSCs),
received any in vivo T-cell depleting antibodies, or non-myeloablative conditioning.

2. Has active cerebral/meningeal disease, active cytomegalovirus (CMV) colitis, or signs
and symptoms of progressive multifocal leukoencephalopathy (PML) or any history of
PML.

3. Is undergoing transplant for the treatment of nonmalignant hematological disorders
(for example: aplastic anemia, sickle cell anemia, thalassemias, Fanconi anemia).