Clinical trial NCT02150551: Safety and Tolerability Of Allogeneic Mesenchymal Stromal Cells in Pediatric Inflammatory Bowel Disease
Official title: Safety and Tolerability Of Allogeneic Mesenchymal Stromal Cells in Pediatric Inflammatory Bowel Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Inflammatory Bowel Diseases
Keywords: Crohn disease
ulcerative colitis
mesenchymal stromal cells
inflammatory bowel diseases
Lead sponsor: Children's National Research Institute
Sponsor class: OTHER
First posted: 2014-05-30
Enrollment: 1
Sex: ALL
Minimum age (years): 12
Maximum age (years): 22
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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.

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

Primary outcomes:
measure: Number of Subjects Who Experience Serious Adverse Events, Adverse Events, and/or Early Treatment Discontinuations.
timeFrame: 45 days after the last infusion
Secondary outcomes:
measure: Proportion of Patients With Clinical Response
timeFrame: 45 days after last infusion
measure: Number of Subjects Demonstrating an Improvement of Laboratory Tests Reflecting Systemic Inflammation.
timeFrame: 45 days after last infusion
Other outcomes:
Locations:
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
Study officials:
affiliation: Children's National Research Institute
name: Laurie S. Conklin, M.D.
role: PRINCIPAL_INVESTIGATOR
References: