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

Primary Purpose

Inflammatory Bowel Diseases

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Allogeneic bone marrow-derived mesenchymal stromal cells

About this trial

This is an interventional treatment trial for Inflammatory Bowel Diseases focused on measuring Crohn disease, ulcerative colitis, mesenchymal stromal cells, inflammatory bowel diseases

Eligibility Criteria

12 Years - 22 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Children's National Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Mesenchymal Stromal Cells (MSCs)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Proportion of Patients With Clinical Response

Proportion of subjects that achieve a clinical response by 45 days after last infusion, 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).

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

Improvement in laboratory parameters (i.e. C-reactive protein, fecal calprotectin, anti-HLA antibodies, and viral specific T-cell activity)

Full Information

NCT ID

NCT02150551

First Posted

January 10, 2014

Last Updated

April 20, 2022

Sponsor

Catherine Bollard

1. Study Identification

Unique Protocol Identification Number

NCT02150551

Brief Title

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

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Completed

Study Start Date

June 7, 2018 (Actual)

Primary Completion Date

September 27, 2019 (Actual)

Study Completion Date

September 27, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Catherine Bollard

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Inflammatory Bowel Diseases

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

1 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Mesenchymal Stromal Cells (MSCs)

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Allogeneic bone marrow-derived mesenchymal stromal cells

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Description

Time Frame

45 days after the last infusion

Secondary Outcome Measure Information:

Title

Proportion of Patients With Clinical Response

Description

Time Frame

45 days after last infusion

Title

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

Description

Improvement in laboratory parameters (i.e. C-reactive protein, fecal calprotectin, anti-HLA antibodies, and viral specific T-cell activity)

Time Frame

45 days after last infusion

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Maximum Age & Unit of Time

22 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Laurie S. Conklin, M.D.

Organizational Affiliation

Children's National Research Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Children's National Medical Center

City

Washington

State/Province

District of Columbia

ZIP/Postal Code

20010

Country

United States

12. IPD Sharing Statement

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

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