Treatment of Severe Osteogenesis Imperfecta by Allogeneic Bone Marrow Transplantation

This study has been completed.
Sponsor:
Information provided by:
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT00705120
First received: June 23, 2008
Last updated: NA
Last verified: June 2008
History: No changes posted
  Purpose

This protocol was a prospective, Phase I study of allogeneic bone marrow transplantation (BMT) as the primary therapy for Osteogenesis Imperfecta Types II and III. Compatible sibling donors and unrelated donors were stratified and analyzed according to the type of donor. All patients with a sibling donor will received a chemotherapy conditioning regimen; a non-T cell depleted allogeneic marrow, and GVHD prophylaxis. All patients with an unrelated donor will receive a chemoradiotherapy conditioning regimen, a T-cell depleted allogeneic marrow, and GVHD prophylaxis. The primary objective of this study was to investigate the safety and toxicity of these BMT procedures in this particular population.


Condition Intervention Phase
Osteogenesis Imperfecta
Other: Bone Marrow Cell Transplantation
Radiation: Irradiation, Total Body
Drug: Cyclophosphamide
Drug: Cyclosporin
Procedure: Mesenchymal Stem Cell Transplantation
Drug: Busulfan
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treatment of Severe (Types II and III) Osteogenesis Imperfecta by Allogeneic Bone Marrow Transplantation

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • To investigate the safety and toxicity of allogeneic bone marrow transplantation (BMT) in children with severe Osteogenesis Imperfecta (OI) [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Enrollment: 9
Study Start Date: November 1995
Study Completion Date: October 2007
Primary Completion Date: July 2000 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1 Other: Bone Marrow Cell Transplantation Drug: Cyclophosphamide Drug: Cyclosporin Procedure: Mesenchymal Stem Cell Transplantation Drug: Busulfan
2 Other: Bone Marrow Cell Transplantation Radiation: Irradiation, Total Body Drug: Cyclophosphamide Procedure: Mesenchymal Stem Cell Transplantation Drug: Busulfan

Detailed Description:

The secondary objective of the protocol assessed the engraftment of donor mesenchymal cells and their ability to increase the synthesis of normal type I procollagen relative to the synthesis of mutated type I procollagen and to assess whether BMT improves the bone structure and the clinical condition of these patients with OI.

  Eligibility

Ages Eligible for Study:   3 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient has diagnosis of OI Type II or III. Because there are no specific, defined clinical criteria consistently used to make this diagnosis, we provide the following clinical guidelines to assist in diagnosis. Any appropriate combinations of the following clinical findings will be acceptable.

Diagnosis of OI Type II

  • Antenatal ultrasonography (if performed for other indications) by established obstetric impressions including short femurs, a small thoracic cage and poorly mineralized bones. Analysis of collagen synthesized from cultured cells obtained from chorionic villus sampling (CVS) may establish the diagnosis; however, no CVS will be performed specifically for enrollment into this study.
  • Clinical examination including prematurity, low birth weight, characteristic facies (blue sclera, beaked nose, extremely soft calvarium), "frog-leg" hips, small thoracic cavity, fractures at birth or shortly thereafter, loose skin or lax joints that cannot be readily explained by other factors.
  • Radiographic evaluation demonstrating various aspects of the characteristic picture of telescoped femur, bowed tibias, beaded ribs, flattened vertebral bodies and virtual absence of calvarial mineralization.

Diagnosis of OI Type III

  • Antenatal ultrasonography (performed for other indications) by established obstetric impressions for this more moderate form of OI. Chorionic villus sampling will be accepted as above.
  • Clinical examination including short stature, bony deformities, many fractures at birth or shortly thereafter. Blue scleras and dental abnormalities are also common.
  • Radiographic abnormalities including thin, osteopenic bones of the limbs with evidence of fractures, growth plate abnormalities, and an undermineralized calvarium.
  • Diagnosis of other diseases with possibly similar presentation to OI (e.g. hypophosphatasia and rickets) should be excluded by obtaining a serum calcium, phosphate and alkaline phosphatase. These parameters can be expected to be within normal limits (alkaline phosphatase may be somewhat elevated) in patients with OI.
  • Age less than 3 years at time of transplant.
  • Parents or legal guardians must sign an informed consent indicating that they are aware this is a research study and have been told of its possible benefits and toxic side effects, including treatment related mortality. Patients or their guardians will be given a copy of the consent form.
  • Identification of a suitable bone marrow donor.
  • Any donor must be of sufficient size so that adequate bone marrow may be harvested.
  • HLA mismatched sibling or unrelated donor. DNA typing will be per- formed on unrelated donors. Donors must be a 6/6 match or a 5/6 match (with serologic mismatch at a single Class I allele or mismatch at a single DR1 allele).

Exclusion Criteria:

  • Patients who are ventilatory dependent due to primary lung parenchymal disease prior to BMT.
  • Patients with evidence of basilar invagination/compression.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00705120

Locations
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Sponsors and Collaborators
St. Jude Children's Research Hospital
Investigators
Principal Investigator: Kimberly Kasow, DO St. Jude Children's Research Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Edwin M Horwitz, MD, PhD, St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT00705120     History of Changes
Other Study ID Numbers: TOIT
Study First Received: June 23, 2008
Last Updated: June 23, 2008
Health Authority: United States: Institutional Review Board

Keywords provided by St. Jude Children's Research Hospital:
Osteogenesis Imperfecta
Bone Marrow Cell Transplantation
Mesenchymal Stem Cells
Stem Cell Transplantation, Mesenchymal

Additional relevant MeSH terms:
Osteogenesis Imperfecta
Osteochondrodysplasias
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Genetic Diseases, Inborn
Collagen Diseases
Connective Tissue Diseases
Cyclophosphamide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on September 18, 2014