Repeated Infusions of Mesenchymal Stromal Cells in Children With Osteogenesis Imperfecta

NCT01061099 | Completed Phase 1

• 1 other identifier: 2008-4-5947
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Osteogenesis Imperfecta Type II; Osteogenesis Imperfecta Type III

Keywords

Type II or Type III Osteogenesis imperfecta; OI; Mesenchymal Stromal Cells; MSC

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• 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

Study Arms (2)

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.

Biological: Mesenchymal Stromal Cells

Stratum B

ACTIVE COMPARATOR

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

Biological: Mesenchymal Stromal Cells

Interventions

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

Also known as: ex-vivo expanded MSCs

Stratum A; Stratum B

Eligibility Criteria

• Age: Up to 19 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• Dependent on supplemental oxygen
• Concurrent Infection

Sponsors & Collaborators

• Nationwide Children's Hospital: lead

Study Sites (1)

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (3)

• 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.

  PMID: 12084934 BACKGROUND

• 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.

  PMID: 11222364 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.

  PMID: 10086387 BACKGROUND

MeSH Terms

Conditions

Osteogenesis Imperfecta; Osteogenesis imperfecta, type 3

Condition Hierarchy (Ancestors)

Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Collagen Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Study Officials

• Alix Seif, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Attending Physician

Study Record Dates

• First Submitted: February 1, 2010
• First Posted: February 2, 2010
• Study Start: February 1, 2010
• Primary Completion: March 1, 2013
• Study Completion: February 1, 2014
• Last Updated: April 24, 2015

Record last verified: 2015-04

Locations

US (1)