NCT00705120

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
9

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Nov 1995

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 1995

Completed
4.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2000

Completed
7.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2007

Completed
9 months until next milestone

First Submitted

Initial submission to the registry

June 23, 2008

Completed
2 days until next milestone

First Posted

Study publicly available on registry

June 25, 2008

Completed
Last Updated

June 25, 2008

Status Verified

June 1, 2008

Enrollment Period

4.7 years

First QC Date

June 23, 2008

Last Update Submit

June 23, 2008

Conditions

Keywords

Osteogenesis ImperfectaBone Marrow Cell TransplantationMesenchymal Stem CellsStem Cell Transplantation, Mesenchymal

Outcome Measures

Primary Outcomes (1)

  • To investigate the safety and toxicity of allogeneic bone marrow transplantation (BMT) in children with severe Osteogenesis Imperfecta (OI)

    1 year

Study Arms (2)

1

OTHER
Other: Bone Marrow Cell TransplantationDrug: CyclophosphamideDrug: CyclosporinProcedure: Mesenchymal Stem Cell TransplantationDrug: Busulfan

2

OTHER
Other: Bone Marrow Cell TransplantationRadiation: Irradiation, Total BodyDrug: CyclophosphamideProcedure: Mesenchymal Stem Cell TransplantationDrug: Busulfan

Interventions

Eligibility Criteria

Age3 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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).

You may not qualify if:

  • Patients who are ventilatory dependent due to primary lung parenchymal disease prior to BMT.
  • Patients with evidence of basilar invagination/compression.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Links

MeSH Terms

Conditions

Osteogenesis Imperfecta

Interventions

Bone Marrow TransplantationWhole-Body IrradiationCyclophosphamideCyclosporineMesenchymal Stem Cell TransplantationBusulfan

Condition Hierarchy (Ancestors)

OsteochondrodysplasiasBone Diseases, DevelopmentalBone DiseasesMusculoskeletal DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesCollagen DiseasesConnective Tissue DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Tissue TransplantationCell- and Tissue-Based TherapyBiological TherapyTherapeuticsTransplantationSurgical Procedures, OperativeRadiotherapyInvestigative TechniquesPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsCyclosporinsPeptides, CyclicMacrocyclic CompoundsPolycyclic CompoundsPeptidesAmino Acids, Peptides, and ProteinsStem Cell TransplantationCell TransplantationButylene GlycolsGlycolsAlcoholsMesylatesAlkanesulfonatesAlkanesulfonic AcidsAlkanesHydrocarbons, AcyclicSulfonic AcidsSulfur AcidsSulfur Compounds

Study Officials

  • Kimberly Kasow, DO

    St. Jude Children's Research Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER

Study Record Dates

First Submitted

June 23, 2008

First Posted

June 25, 2008

Study Start

November 1, 1995

Primary Completion

July 1, 2000

Study Completion

October 1, 2007

Last Updated

June 25, 2008

Record last verified: 2008-06

Locations