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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Stratum A | Active Comparator | Subjects with a diagnosis of Type II or Type III osteogenesis imperfecta who have previously undergone a bone marrow transplant. Intervention: Mesenchymal Stromal Cells. |
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| Stratum B | Active Comparator | Subjects with Type II or III osteogenesis imperfecta who have not undergone a bone marrow transplant. Intervention: Mesenchymal Stromal Cells. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Mesenchymal Stromal Cells | Biological | 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 |
| 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 |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Alix Seif, MD | Children's Hospital of Philadelphia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12084934 | Background | Horwitz EM, Gordon PL, Koo WK, Marx JC, Neel MD, McNall RY, Muul L, Hofmann T. Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone. Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8932-7. doi: 10.1073/pnas.132252399. | |
| 11222364 |
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| ID | Term |
|---|---|
| D010013 | Osteogenesis Imperfecta |
| C536044 | Osteogenesis imperfecta, type 3 |
| ID | Term |
|---|---|
| D010009 | Osteochondrodysplasias |
| D001848 | Bone Diseases, Developmental |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
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| Completion of Study |
| Horwitz EM, Prockop DJ, Gordon PL, Koo WW, Fitzpatrick LA, Neel MD, McCarville ME, Orchard PJ, Pyeritz RE, Brenner MK. Clinical responses to bone marrow transplantation in children with severe osteogenesis imperfecta. Blood. 2001 Mar 1;97(5):1227-31. doi: 10.1182/blood.v97.5.1227. |
| 10086387 | Background | Horwitz EM, Prockop DJ, Fitzpatrick LA, Koo WW, Gordon PL, Neel M, Sussman M, Orchard P, Marx JC, Pyeritz RE, Brenner MK. Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med. 1999 Mar;5(3):309-13. doi: 10.1038/6529. |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D003095 | Collagen Diseases |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |