Safety and Tolerability Of Allogeneic Mesenchymal Stromal Cells in Pediatric Inflammatory Bowel Disease

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. Mesenchymal stromal cells support the development of
blood cells within the bone marrow. They have also 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.

Investigators will culture donated bone marrow mesenchymal stromal cells in a unique
automated system, and infuse the cells in a fresh, replicating stage of growth. This study is
to test the safety and tolerability of donor mesenchymal stromal cells in children with
Inflammatory Bowel Disease.

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