Study of Mesenchymal Stem Cells for Pediatric Perianal Fistulizing Crohn's Disease

Study Overview
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Brief Summary
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This study plans to enroll 10 patients aged 13-17 years of age with refractory perianal fistulizing disease. Patients will be treated by direct injection to the fistula tract(s) with 75 million allogeneic bone marrow derived mesenchymal stem cells at baseline and again after 3 months if not completely healed.

Detailed Description
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Crohn's disease (CD), a chronic transmural inflammatory disease of the gastrointestinal tract, continues to increase in incidence for unknown reasons. According to population based studies, at least 26% of patients with CD will develop perianal fistulas in the first two decades following diagnosis, particularly those with colonic and rectal involvement. These patients experience significant morbidity due to pain, persistent drainage, recurrent perianal sepsis, and ongoing need to access medical care resulting in increased costs and impaired quality of life. Onset of Crohn's disease in childhood is associated with even more aggressive perianal fistula development, with fistulas occurring in as many as 20-31% of children within 5-7 years after Crohn's disease diagnosis. Based on national estimates of pediatric Crohn's disease prevalence, this suggests that there are more than 10,000 children with perianal fistulas due to Crohn's disease in the United States. This study plans to enroll 10 patients (aged 13-17 years) with refractory perianal fistulizing disease. The next step in management for these patients would be a mucosal tissue flap, temporary stoma, or proctectomy with permanent ostomy. Patients will be treated by direct injection of 75 million allogeneic bone marrow derived mesenchymal stem cells at baseline and again after 3 months if not completely healed. Patients will be followed for a total of 12 months post initial injection.

Official Title
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A Phase I Study of Adult Allogeneic Bone Marrow Derived Mesenchymal Stem Cells for Pediatric Perianal Fistulizing Crohn's Disease

Conditions
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Perianal Fistula Due to Crohn's Disease (Disorder)

Intervention / Treatment
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* Drug: Mesenchymal stem cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Males and females aged 13-17 with a diagnosis of Crohn's disease for at least six months duration. Single and Multi-tract Perianal fistula, with or without previous failed surgical repair. Have no contraindications to MR evaluations: e.g. pacemaker or magnetically active metal fragments, claustrophobia Ability to comply with protocol Competent and able to provide written informed consent Concurrent Crohn's-related therapies with stable doses corticosteroids, 5- ASA drugs, immunomodulators, anti-TNF therapy, anti-integrin and anti-interleukin therapies are permitted. Agree to use birth control or abstinence to avoid pregnancy during the study Exclusion Criteria Inability to give informed consent. Clinically significant medical conditions within the six months before administration of MSCs: e.g. myocardial infarction, active angina, congestive heart failure or other conditions that would, in the opinion of the investigators, compromise the safety of the subject. Specific exclusions: Hepatitis B or C HIV Abnormal AST or ALT at screening (defined as >/+2x ULN) History of colon cancer in the past two years, or treatment for other cancers within the last 6 months. Investigational drug within one month of treatment Pregnant or breast feeding or trying to become pregnant. Presence of a rectovaginal or perineal body fistula Change in Crohn's immunosuppressive regimen within the 2 months prior to enrollment Uncontrolled intestinal Crohn's disease which will require escalation for medical therapy or surgery within 2 months of enrollment Severe anal canal disease that is stenotic and requires dilation Female participant unwilling to agree to use acceptable contraception methods during participation in study

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mesenchymal stem cells<br>allogeneic bone marrow derived mesenchymal stem cells | Drug: Mesenchymal stem cells<br>* Direct injection of 75 million allogeneic bone marrow derived mesenchymal stem cells at baseline and again after 3 months if not completely healed<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment related adverse events | Number of participants with treatment related adverse events post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease as assessed by protocol | Month 3 | 
| Treatment related adverse events | Number of participants with treatment related adverse events post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease as assessed by protocol | Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete clinical healing | Number of participants with complete clinical healing post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease. Complete Healing is defined as: Radiographic Healing: MRI with an absence of a fluid collection >2 cm in 3 of 3 dimensions, lack of edema, inflammation or sign of active inflammatory response. A remnant scar of a fistula tract may remain Clinical Healing: 100% cessation of drainage on both clinical exam with deep palpation and per patient report and epithelization of the external fistula opening | Month 3 | 
| Complete clinical healing | Number of participants with complete clinical healing post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease. Complete Healing is defined as: Radiographic Healing: MRI with an absence of a fluid collection >2 cm in 3 of 3 dimensions, lack of edema, inflammation or sign of active inflammatory response. A remnant scar of a fistula tract may remain Clinical Healing: 100% cessation of drainage on both clinical exam with deep palpation and per patient report and epithelization of the external fistula opening | Month 12 | 
| Partial clinical healing | Number of participants with partial clinical healing post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease Partial clinical healing is defined as: Radiographic Healing: MRI with an absence of a fluid collection >2 cm in 2 of 3 dimensions, lack of edema, inflammation or sign of active inflammatory response. A remnant scar of a fistula tract may remain Clinical healing: Greater than or equal to 50 % cessation of drainage on both clinical exam with deep palpation and per patient report and epithelization of the external fistula opening | Month 3 | 
| Partial clinical healing | Number of participants with partial clinical healing post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease Partial clinical healing is defined as: Radiographic Healing: MRI with an absence of a fluid collection >2 cm in 2 of 3 dimensions, lack of edema, inflammation or sign of active inflammatory response. A remnant scar of a fistula tract may remain Clinical healing: Greater than or equal to 50 % cessation of drainage on both clinical exam with deep palpation and per patient report and epithelization of the external fistula opening | Month 12 | 
| Lack of response | Number of participants with lack of response post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease Lack of response is defined as: Radiographic and Clinical healing which does not meet the threshold for Partial Healing | Month 3 | 
| Lack of response | Number of participants with lack of response post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease Lack of response is defined as: Radiographic and Clinical healing which does not meet the threshold for Partial Healing | Month 12 | 
| Worsening of disease | Number of participants with worsening of disease post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease Worsening disease is defined as: Radiographic: MRI with a fluid collection >2 cm in 2 of 3 dimensions, edema, inflammation or sign of active inflammatory response. An increased number of tracts may be seen, or increased branching from the primary tract, Clinical: Increased drainage per patient report and on clinical exam | Month 3 | 
| Worsening of disease | Number of participants with worsening of disease post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease Worsening disease is defined as: Radiographic: MRI with a fluid collection >2 cm in 2 of 3 dimensions, edema, inflammation or sign of active inflammatory response. An increased number of tracts may be seen, or increased branching from the primary tract, Clinical: Increased drainage per patient report and on clinical exam | Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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perianal, fistula, pediatric, crohn's disease