Phase II Trial of Natalizumab + Prednisone for Initial Therapy of Acute GI GVHD
Condition: Graft Versus Host Disease
MeSH terms: Graft vs Host Disease
Intervention: Natalizumab; Methylprednisolone
Intervention MeSH terms: Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Natalizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Graft Versus Host Disease

Summary:

      This research study is a Phase II clinical trial, which tests the safety and effectiveness of
      an investigational drug Natalizumab in treating Acute Graft-Versus-Host Disease (GVHD) in the
      Gastrointestinal (GI) Tract.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants must meet the following criteria on screening examination to be eligible
             to participate in the study:

          -  Participants must have acute Graft-Versus-Host Disease (GVHD) of the lower
             gastrointestinal tract as defined by the clinical impression of the treating
             physician, requiring systemic treatment. Minimum criteria for GI GVHD includes
             diarrhea of greater than 500 mL/day. Biopsy of the GI tract is required for study
             entry and must confirm the diagnosis of acute GVHD. Stool samples to rule out
             infectious causes of diarrhea, including norovirus, Clostridium difficile and other
             clinically indicated infections must also be negative. Eligibility includes:

          -  Acute GVHD developing after allogeneic hematopoietic stem cell transplantation (HSCT)
             using bone marrow, peripheral blood stem cells, or umbilical cord blood. Recipients of
             non-myeloablative, reduced intensity and myeloablative transplants are eligible.

          -  Patients who develop acute GVHD after donor lymphocyte infusion (DLI) are eligible.

          -  There is no specified time window after day 0 of transplant as acute GVHD is only
             defined by clinical manifestations.

          -  Patients must have experienced neutrophil engraftment after HSCT as defined by
             absolute neutrophil counts ≥ 500 / µL × 3 consecutive measurements. Absolute
             neutrophil count (ANC) should be calculated using the standard formula (Neut +
             Bands)(WBC × 101).

          -  The presence of hepatic, upper GI and/or cutaneous acute GVHD is permitted.

          -  Steroids can be started up to 7 days prior to the administration of natalizumab.

          -  Age ≥ 18

          -  Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria

          -  Participants who exhibit any of the following conditions at screening will not be
             eligible for admission into the study:

          -  Patients with the entity of Acute/Chronic GVHD overlap syndromes.

          -  Requiring mechanical ventilation

          -  Vasopressor requirement

          -  Concurrent hepatic veno-occlusive disease (VOD) based on clinical examination

          -  Karnofsky performance status < 30

          -  Participants may not be receiving any other study agents for at least 7 days prior to
             enrollment

          -  Prior use of natalizumab for any reason is not allowed

          -  Pregnant women are excluded from this study because of the potential teratogenic
             effects of natalizumab. Because natalizumab enters breast milk, and the effect is
             unknown in infants, breastfeeding should be discontinued if the mother is treated with
             natalizumab.