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

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ClinicalTrials.gov Identifier: NCT02150551
Recruitment Status : Recruiting
First Posted : May 30, 2014
Last Update Posted : August 22, 2017
Sponsor:
Information provided by (Responsible Party):
Catherine Bollard, Children's Research Institute

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.


Condition or disease Intervention/treatment Phase
Inflammatory Bowel Diseases Biological: Allogeneic bone marrow-derived mesenchymal stromal cells Phase 1

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety and Tolerability Of Allogeneic Mesenchymal Stromal Cells in Pediatric Inflammatory Bowel Disease
Study Start Date : September 2015
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : November 2020

Arm Intervention/treatment
Experimental: Fixed dose
All patients will receive 8 weekly infusions of allogeneic bone marrow-derived mesenchymal stromal cells.
Biological: Allogeneic bone marrow-derived mesenchymal stromal cells
A fixed dose will be studied: 1 x 106 cells/kg administered intravenously (IV) weekly for 8 consecutive weeks. Toxicity will be monitored, using the department specific Standard Operating Procedure (SOP).




Primary Outcome Measures :
  1. Number of subjects who experience serious adverse events, adverse events, and/or early treatment discontinuations. [ Time Frame: 8 weeks. ]
    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.


Secondary Outcome Measures :
  1. Proportion of patients with clinical response [ Time Frame: 45 days post treatment ]
    Proportion of subjects that achieve a clinical response by 45 days post-treatment, as defined by a decrease in PCDAI from baseline by greater than or equal to 12.5 points (for CD) or a decrease in PUCAI of greater than or equal to 20 points (for UC).

  2. Number of subjects showing mprovement in quality of life with the intervention. [ Time Frame: Baseline and about day 77 ]
    Quality of life in pediatric patients with IBD is measured using the IMPACT III IBD questionnaire.

  3. Number of subjects demonstrating an improvement of laboratory tests reflecting systemic inflammation. [ Time Frame: Baseline and about day 77 ]
    Improvement in laboratory parameters (i.e. C-reactive protein, fecal calprotectin, pro-inflammatory cytokines)

  4. Number of subjects with endoscopic healing after treatment. [ Time Frame: Baseline and about day 77. ]
    Proportion of subjects with endoscopic improvement, as assessed by change in baseline endoscopic scores (Simple Endoscopic Score Crohn's Disease [SES-CD] for CD or Endoscopic SubScore within the Mayo Score for UC)



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Ages Eligible for Study:   5 Years to 22 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must be age 5 years to 22 years, inclusive
  • Patients must have moderate-severely active CD or UC, and documented active disease on colonoscopy or MR enterography within the preceding 2 months.
  • Patients must have a PCDAI >30 or PUCAI >34
  • Patients who have failed or are intolerant to standard therapy for moderate-severely active CD or UC. Standard therapy is defined as corticosteroid induction with maintenance immunomodulator therapy (mercaptopurine, azathioprine, or methotrexate), and/or induction and treatment with a biologic (i.e. infliximab or adalimumab). Specifically, the patient will have recurrence or persistence of symptoms despite treatment with 1) steroids for at least 4 weeks, initiated at least 1 mg/kg/dose and delivered intravenously or orally, with taper to at least 20 mg or 0.5 mg/kg/day by the time of enrollment; OR 2) oral budesonide 9 mg daily for at least 4 weeks AND treatment with maintenance mercaptopurine/azathioprine or methotrexate, and/or 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), or immunomodulators (if the dose has been unchanged for the past 3 months for mercaptopurine/azathioprine and 2 months for methotrexate) during the study. Doses of these medications should remain stable during the 8 week study

Exclusion Criteria:

  • Patients < 5 years of age or >22 years of age
  • Biologic therapy (i.e. infliximab or adalimumab) in the preceding 8 weeks.
  • 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 8 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
  • 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 2.0 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 6 months of enrollment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02150551


Contacts
Contact: Laurie S. Conklin, M.D. 202-476-3032 lconklin@childrensnational.org
Contact: Catherine Bollard, M.D. 202-476-4776 cbollard@childrensnational.org

Locations
United States, District of Columbia
Children's National Medical Center Recruiting
Washington, D.C., District of Columbia, United States, 20010
Contact: Conklin S. Conklin, M.D.    202-476-3032    lconklin@childrensnational.org   
Principal Investigator: Laurie S. Conklin, M.D.         
Sponsors and Collaborators
Catherine Bollard
Investigators
Principal Investigator: Laurie S. Conklin, M.D. Children's Research Institute

Responsible Party: Catherine Bollard, Director- Center for Emerging Technologies in Immune Cell Therapies (CETI), Children's Research Institute
ClinicalTrials.gov Identifier: NCT02150551     History of Changes
Other Study ID Numbers: STOMP
First Posted: May 30, 2014    Key Record Dates
Last Update Posted: August 22, 2017
Last Verified: August 2017

Keywords provided by Catherine Bollard, Children's Research Institute:
Crohn disease
ulcerative colitis
mesenchymal stromal cells
inflammatory bowel diseases

Additional relevant MeSH terms:
Intestinal Diseases
Inflammatory Bowel Diseases
Gastrointestinal Diseases
Digestive System Diseases
Gastroenteritis