Dose Finding Study of Vedolizumab for GvHD in Participants Undergoing Allogeneic HSCT
Condition: Allogeneic Hematopoietic Stem Cell Transplantation
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to assess the initial tolerability, safety and recommended phase
      2 dose of vedolizumab intravenous (IV) administered for GvHD prophylaxis along with standard
      GvHD prophylaxis therapy (in participants undergoing allogeneic hematopoietic stem cell
      transplantation [allo-HSCT]).
    

Detailed description: 
      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
      ulcerative colitis (UC) and Crohn's disease (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.
    

Intervention name(s): Vedolizumab
Intervention type(s): Drug
Intervention description(s): Vedolizumab Injection.
Intervention MeSH terms: Vedolizumab
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Drug Therapy