Gut Decontamination In Pediatric Allogeneic Hematopoietic
Condition: Hematopoietic Stem Cell Transplantation (HSCT); Acute GVH Disease
MeSH terms: Graft vs Host Disease
Intervention: Vancomycin-polymyxin B
Intervention MeSH terms: Vancomycin; Polymyxins; Polymyxin B
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 4 Years
Maximum age: 30 Years
Healthy volunteers: No
Keywords: Hematopoietic Stem Cell Transplantation (HSCT); Acute GVH Disease

Summary:

      This research study is for participants who are undergoing allogeneic hematopoietic stem cell
      transplantation (HSCT) and are at risk for developing acute graft-versus-host disease (GVHD).
      GVHD is a complication of HSCT in which immune cells from the donor cause inflammation and
      injury to tissues and organs of the HSCT recipient. Vancomycin-polymyxin B (commonly called
      "vancopoly") is an oral antibiotic that is given to people undergoing allogeneic HSCT as a
      preventive measure for acute GVHD. This research study is studying the effects of vancopoly
      on the microorganisms living in the intestine during and after stem cell transplantation.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Eligibility Criteria for Patients Undergoing Allogeneic HSCT

               -  Recipient of 9/10 or 10/10 (HLA-A, -B, -C, -DRB1, -DQB1) matched bone marrow
                  allogeneic hematopoietic stem cell transplantation (HSCT) OR 4/6, 5/6 and 6/6
                  (HLA-A, -B, -DR) matched cord blood allogeneic HSCT.

               -  Participants may have underlying malignant or non-malignant hematologic disease,
                  except for primary immunodeficiency, as the indication for their allogeneic HSCT.
                  Patients with immune dysregulation such as familial or secondary hemophagocytic
                  lymphohistiocytosis (HLH) are eligible.

               -  Participants must may receive either a myeloablative or
                  non-myeloablative(reduced-intensity) conditioning regimen. Anti-thymocyte
                  globulin (ATG) in the conditioning regimen is permitted.

               -  Graft-versus-host disease (GVHD) prophylaxis with any of the following agents:
                  calcineurin inhibitor, and short-course methotrexate, with or without steroids,
                  mycophenolate mofetil, and sirolimus.

               -  Age ≥ 4 years old and toilet-trained. Participants must be able to deposit stool
                  samples directly into stool collection containers. Stool specimens from diapers
                  are difficult to obtain and are prone to more sampling error, particularly for
                  loose or liquid stools which are common in the peri-transplant period.

               -  Lansky/Karnofsky performance status ≥60% (see Appendix A)

               -  Ability to understand and/or the willingness of their parent or legally
                  authorized representative to sign a written informed consent document

          -  Eligibility Criteria for Healthy Bone Marrow Donors

               -  Healthy individuals, ages ≥ 4 years and toilet-trained, who have been identified
                  by BCH or DFCI providers as 9/10 or 10/10 (HLA-A, -B, -C, -DRB1, -DQB1 matched
                  bone marrow donors for transplantation will also be eligible to participate in
                  this study.

        Exclusion Criteria:

          -  Patients undergoing allogeneic HSCT for correction of a primary immunodeficiency
             disorder (e.g. SCID).

          -  Patients with age ≤ 10 years undergoing HSCT with a matched sibling donor. These
             patients are at very low risk of acute GVHD and do not receive gut decontamination per
             our institutional standard practice.

          -  Participants receiving GVHD prophylaxis with drugs other than calcineurin inhibitors,
             methotrexate or steroids.agents listed above (e.g. abatacept).

          -  History of allergic reactions attributed to oral vancomycin or oral polymyxin B.

          -  Participants undergoing active therapy for immune-mediated or infectious colitis upon
             admission for allogeneic HSCT.

          -  Participants receiving antibiotic therapy for treatment of a bacterial infection or
             bacterial prophylaxis upon admission for allogeneic HSCT. Use of any agent (e.g.
             sulfamethoxazole/trimethoprim) for prophylaxis of Pneumocystis jirovecii pneumonia is
             permitted. Concurrent use of anti-fungal and anti-viral therapies is also permitted.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection or psychiatric illness/social situations that would limit compliance with
             study requirements.