Repeated Infusions of Mesenchymal Stromal Cells in Children With Osteogenesis Imperfecta

NCT ID: NCT01061099

Last Updated: 2015-04-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-02-28
• Study Completion Date: 2014-02-28

Brief Summary

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

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.

Conditions

Osteogenesis Imperfecta Type II; Osteogenesis Imperfecta Type III

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Stratum A

Subjects with a diagnosis of Type II or Type III osteogenesis imperfecta who have previously undergone a bone marrow transplant. Intervention: Mesenchymal Stromal Cells.

Group Type: ACTIVE_COMPARATOR

Mesenchymal Stromal Cells

Intervention Type: 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

Stratum B

Subjects with Type II or III osteogenesis imperfecta who have not undergone a bone marrow transplant. Intervention: Mesenchymal Stromal Cells.

Group Type: ACTIVE_COMPARATOR

Mesenchymal Stromal Cells

Intervention Type: 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

Interventions

Mesenchymal Stromal Cells

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

Intervention Type: BIOLOGICAL

Other Intervention Names

ex-vivo expanded MSCs

Eligibility Criteria

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

• Maximum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nationwide Children's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Edwin Horwitz

Attending Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Alix Seif, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Locations

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 12084934 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11222364 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 10086387 (View on PubMed)

Other Identifiers

2008-4-5947

Identifier Type: -

Identifier Source: org_study_id