Allogeneic Hematopoietic Cell Transplantation to Correct the Biochemical Defect and Create Tolerance to Donor Tissue in Subjects With Epidermolysis Bullosa
N/A
25 Years
Both
Epidermolysis Bullosa
Trial Information
Allogeneic Hematopoietic Cell Transplantation to Correct the Biochemical Defect and Create Tolerance to Donor Tissue in Subjects With Epidermolysis Bullosa
OBJECTIVES:
Primary
- Estimate the incidence of detectable donor-derived collagen type VII at day 100 in
patients with epidermolysis bullosa by donor.
Secondary
- Determine the incidence of transplant-related mortality at day 180
- Determine the incidence of blood chimerism at days 21, 100, 180, 365, and 730
- Determine the incidence of neutrophil recovery at day 42 and platelet recovery at day
180
- Determine the incidence of acute graft-versus-host disease (GVHD) grade II-IV and grade
III-IV at day 100
- Determine the incidence of chronic GVHD at 1 year
- Determine the probability of survival at 1 and 2 years
- Determine the incidence of donor derived cells in the skin
- Determine resistance to blister formation OUTLINE: This is an open-label, pilot study.
- Conditioning regimen: Busulfan intravenously (IV) over 2 hours every 6 hours on days -9
to -4, fludarabine phosphate IV over 1 hour on days -5 to -3, and high-dose
cyclophosphamide IV over 1 hour on days -5 to -2.
- Stem cell transplantation on day 0.
After completion of study treatment, patients are followed periodically for at least 5
years.
PROJECTED ACCRUAL: 30 patients
Inclusion Criteria
Inclusion criteria:
- Diagnosis of epidermolysis bullosa (EB)
- Documented collagen type VII deficiency by:
- Antigenic mapping (LH7.2 antibody)
- Ultrastructure analysis of anchoring fibrils
- DNA mutation analysis
- Performance status: >50% Lansky; >50% Karnofsky
- Adequate organ function
- Renal: glomerular filtration rate > 60ml/min/1.73m2 patients aged ≤ 10 years
- Hepatic: bilirubin, aspartate aminotransferase/alanine aminotransferase
(AST/ALT), Alkaline phosphatase (ALP) < 5 x upper limit of normal 4.2.3
Pulmonary: oxygen saturation >92% 4.2.4 Cardiac: left ventricular ejection
fraction > 45%.
- Healthy related hematopoietic stem cell donor available and meeting 1 of the
following criteria:
- HLA-A, B, DRB1-identical sibling bone marrow and/or umbilical cord blood donor
(first priority)
- HLA-A, B, DRB1-matched or partially matched related donor (second priority)
- Donor may be a carrier but must be unaffected by EB
- 8/8 HLA A, B, C, DRB1 allele level matched unrelated marrow donor (third
priority)
- 7/8 HLA-A, B, C, DRB1 allele level matched unrelated marrow donor or 4/6 HLA-A,
B (antigen level), DRB1 (allele level) matched unrelated cord blood donor
(fourth priority)
Exclusion criteria:
- Active infection at time of transplantation (including active infection with
Aspergillus or other mold within 30 days)
- Squamous cell carcinoma of the skin
- History of human immunodeficiency virus (HIV) infection
- Prior transplantation with donor skin
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Number of Patients With Detectable Collagen Type VII
Outcome Description:
Number of patients with epidermolysis bullosa who had collagen type VII. Type VII collagen defects cause recessive dystrophic epidermolysis bullosa (RDEB), a blistering skin disorder often accompanied by epidermal cancers.
Outcome Time Frame:
Day 100 Post Transplant
Safety Issue:
No
Principal Investigator
John E. Wagner, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Masonic Cancer Center, University of Minnesota
Authority:
United States: Institutional Review Board
Study ID:
MT2006-15
NCT ID:
NCT00478244
Start Date:
April 2007
Completion Date:
August 2011
Related Keywords:
- Epidermolysis Bullosa
- epidermolysis bullosa
- dystrophic epidermolysis bullosa
- Epidermolysis Bullosa
Name | Location |
|---|---|
| Masonic Cancer Center, University of Minnesota | Minneapolis, Minnesota 55455 |
