Safety and Tolerability Of Allogeneic Mesenchymal Stromal Cells in Pediatric Inflammatory Bowel Disease
Condition: Inflammatory Bowel Diseases
MeSH terms: Intestinal Diseases; Inflammatory Bowel Diseases
Intervention: Allogeneic bone marrow-derived mesenchymal stromal cells
Intervention description: This study is a pilot phase 1 study of patients with moderately to severely active Crohn Disease (CD) and ulcerative colitis (UC) (≥ 18 years, Mayo score: ≥6 or CDAI: ˃ 220; <18 years, Pediatric Crohn's Disease Activity Index (PCDAI) :> 30) or Pediatric Ulcerative Colitis Activity Index (PUCAI) : >34). A fixed dose will be studied: 1 x 106 cells/kg administered intravenously (IV) weekly for 4 consecutive weeks, with the option of an additional 4 weeks of treatment, at the discretion of the principal investigator.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 12 Years
Maximum age: 22 Years
Healthy volunteers: No
Keywords: Crohn disease; ulcerative colitis; mesenchymal stromal cells; inflammatory bowel diseases

Summary:

      In this trial, investigators will infuse donor bone marrow mesenchymal stromal cells
      intravenously, as a treatment for pediatric Crohn's disease or ulcerative colitis that has
      not responded to conventional therapies. The goals of this study are to test the safety and
      tolerability of donor mesenchymal stromal cells in children with Inflammatory Bowel Disease.

      Mesenchymal stromal cells support the development of blood cells within the bone marrow. When
      isolated from a donor and infused into an animal or human, they have been demonstrated to
      travel to areas of inflammation, to alter immune responses, to decrease pro-inflammatory
      cytokines, and to promote tissue repair. Infusion of these cells does not lead to rejection.
      These properties lead investigators to hypothesize that that these may be they may be
      beneficial in treating inflammatory bowel disease.
    

Eligibility criteria:

        Inclusion Criteria:

          -  For the young adult cohort, patients must be ages 17 ≤22 years

          -  For the pediatric cohort, patients must be ages 12 ≤16 years

          -  Patients must have moderate-severely active CD or UC (defined in section 2.3), and
             documented active disease on flexible sigmoidoscopy, colonoscopy or MR enterography
             within the preceding 2 months.

          -  Patients who have failed or are intolerant of biologic therapy. Specifically, the
             patient will have recurrence or persistence of active disease despite current or past
             treatment with a biologic. At the time of enrollment, study subjects may be currently
             receiving 5-aminosalicylates, corticosteroids (≤ 20 mg daily or up to 0.5 mg/kg/day if
             weight <40 kg), methotrexate, 6MP/azathioprine, or a biologic (either as monotherapy
             or in combination). During the treatment phase, if the treating physician thinks that
             a medication dose should be lowered to avoid side effects, this should be recorded.

          -  Patient or parent/guardian capable of providing informed consent.

        Exclusion Criteria:

          -  • Patients < 12 years of age or >22 years of age

          -  Pregnant or breastfeeding. Serum pregnancy test must be negative at screening for
             female subjects of childbearing potential. Urine pregnancy test must remain negative
             at each of 4 infusion visits.

          -  Patients with toxic mega-colon or intestinal perforation

          -  Evidence of autoimmune chronic active hepatitis or sclerosing cholangitis.

          -  Patients with fever > 39° C or clinically significant active infection within 1 week
             (i.e. chronic infections including Hepatitis B/C or HIV or acute infections, including
             urinary tract infection and respiratory tract infection)

          -  Received an agent not approved by the FDA for marketed use in any indication or any
             small molecule inhibitors (i.e. naltrexone) within 60 days of enrollment.

          -  Subjects who are taking greater than 20 mg (or if body weight <40 kg, 0.5 mg/kg) of
             prednisone daily.

          -  Clinically significant abnormal biochemical and hematological parameters, including:

               -  Neutrophil count < 1000 cells/mm3

               -  Hemoglobin < 8 g/dl

               -  Platelet count ≤ 130 cells/mm3

               -  Creatinine ≥ 1.2 x the upper limit of normal

               -  Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≥ 2x the
                  upper limit of normal

               -  Conjugated bilirubin greater than 1.2. mg/dL

          -  Has active infection with enteric pathogens as evidenced by positive microbiological
             culture of stool or C.difficile toxin PCR.

          -  Had bowel surgery other than perianal procedures (fistulotomy, seton placement,
             abscess drainage) within 3 months of enrollment.

          -  Has uveitis

          -  Has known pulmonary disease, excluding mild intermittent asthma