Repeated Infusions of Mesenchymal Stromal Cells in Children With Osteogenesis Imperfecta

Study Overview
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Brief Summary
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This is a study to evaluate the safety and effectiveness of repeated Mesenchymal Stromal Cells (MSC) infusions to patients with Type II or III osteogenesis imperfecta (OI). Participants will receive MSC infusions approximately every 4 months to complete a total of 6 infusions over 20 months. Participants will be followed for 4 months post their last MSC infusion.

Detailed Description
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This is a pilot study to evaluate the safety and efficacy of repeated MSC infusions to subjects with OI. This study will evaluate subjects on two separate strata. Stratum A will include subjects with a diagnosis of Type II or Type III osteogenesis imperfecta who have previously undergone a bone marrow transplant. Stratum A may use previously harvested and cryopreserved bone marrow mononuclear cells from original BMT donor or freshly harvested or cryopreserved bone marrow mononuclear cells obtained from a haploidentical healthy parent or sibling. Stratum B will include subjects with Type II or III osteogenesis imperfecta who have not undergone a bone marrow transplant. Stratum B will only receive freshly harvested or cryopreserved bone marrow mononuclear cells from a haploidentical healthy parent or sibling. Participants will receive MSC infusions approximately every 4 months to complete a total of 6 infusions over 20 months. Participants will be followed for 12 months post their last MSC infusion.

Official Title
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A Pilot Study to Assess the Safety and Feasibility of Repeated Infusions of Mesenchymal Stromal Cells (MSC) in Children With Osteogenesis Imperfecta

Conditions
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Osteogenesis Imperfecta Type II, Osteogenesis Imperfecta Type III

Intervention / Treatment
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* Biological: Mesenchymal Stromal Cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects less than or equal to 19 years of age at the time of enrollment Children with a diagnosis of severe of Type II or III osteogenesis imperfecta Parent or sibling greater than or equal to 18 years of age, donor willing to or has already undergone HLA typing, and willing and able to provide bone marrow BMT greater than 5 years ago for Stratum A Exclusion Criteria: Dependent on supplemental oxygen Concurrent Infection

Ages Eligible for Study
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Maximum Age: 19 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Stratum A<br>Subjects with a diagnosis of Type II or Type III osteogenesis imperfecta who have previously undergone a bone marrow transplant. Intervention: Mesenchymal Stromal Cells. | Biological: Mesenchymal Stromal Cells<br>* Both cohorts will receive multiple infusions of ex-vivo expanded MSCs. Stratum A may use previously harvested and cryopreserved bone marrow mononuclear cells from original BMT donor or freshly harvested or cryopreserved bone marrow mononuclear cells obtained from a haploidentical healthy parent or sibling. Stratum B will only receive freshly harvested or cryopreserved bone marrow<br>* Other names: ex-vivo expanded MSCs;|
| Active Comparator: Stratum B<br>Subjects with Type II or III osteogenesis imperfecta who have not undergone a bone marrow transplant. Intervention: Mesenchymal Stromal Cells. | Biological: Mesenchymal Stromal Cells<br>* Both cohorts will receive multiple infusions of ex-vivo expanded MSCs. Stratum A may use previously harvested and cryopreserved bone marrow mononuclear cells from original BMT donor or freshly harvested or cryopreserved bone marrow mononuclear cells obtained from a haploidentical healthy parent or sibling. Stratum B will only receive freshly harvested or cryopreserved bone marrow<br>* Other names: ex-vivo expanded MSCs;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the safety or repeated infusions of donor-derived and MSCs in subjects with severe osteogenesis imperfecta > 5years after an allogeneic bone marrow transplant and no prior bone marrow transplant. |  | Completion of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine if MSCs elicit an immune response after repeated infusions. |  | Completion of study | 
| To determine the change in clinical course (growth, bone mineral content, fracture rate, development/activities) of subjects after experimental MSC intervention therapy as compared with each subject's own pre-MSC intervention therapy. |  | Completion of Study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type II or Type III Osteogenesis imperfecta, OI, Mesenchymal Stromal Cells, MSC