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

NCT02150551 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: STOMP
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Inflammatory Bowel Diseases

Keywords

Crohn disease; ulcerative colitis; mesenchymal stromal cells; inflammatory bowel diseases

Outcome Measures

Primary Outcomes (1)

• Number of Subjects Who Experience Serious Adverse Events, Adverse Events, and/or Early Treatment Discontinuations.

  Safety and tolerability of the administration of human allogeneic bone marrow-derived stromal cells to children and young adults with IBD, measured by the frequency of any SAEs, AEs and/or early treatment discontinuations. Weekly infusions for 8 weeks, post-treatment assessment 45 days after last infusion, three additional follow-up visits over 2 years.

  45 days after the last infusion

Secondary Outcomes (2)

• Proportion of Patients With Clinical Response

  45 days after last infusion

• Number of Subjects Demonstrating an Improvement of Laboratory Tests Reflecting Systemic Inflammation.

  45 days after last infusion

Study Arms (1)

Mesenchymal Stromal Cells (MSCs)

EXPERIMENTAL

A fixed dose of Mesenchymal Stromal Cells (MSCs) 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.

Biological: Allogeneic bone marrow-derived mesenchymal stromal cells

Interventions

Allogeneic bone marrow-derived mesenchymal stromal cells BIOLOGICAL

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.

Mesenchymal Stromal Cells (MSCs)

Eligibility Criteria

• Age: 12 Years - 22 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Catherine Bollard: lead

Study Sites (1)

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

MeSH Terms

Conditions

Inflammatory Bowel Diseases; Crohn Disease; Colitis, Ulcerative

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Colitis; Colonic Diseases

Results Point of Contact

• Title: Catherine Bollard, MD
• Organization: Children's National Hospital

cbollard@childrensnational.org

202-476-4776

Study Officials

• Laurie S. Conklin, M.D.

  Children's National Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director- Center for Emerging Technologies in Immune Cell Therapies (CETI)

Study Record Dates

• First Submitted: January 10, 2014
• First Posted: May 30, 2014
• Study Start: June 7, 2018
• Primary Completion: September 5, 2018
• Study Completion: September 5, 2018
• Last Updated: May 6, 2024
• Results First Posted: January 20, 2023

Record last verified: 2024-04

Locations

US (1)