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Allogeneic Hematopoietic Cell Transplantation to Correct the Biochemical Defect and Create Tolerance to Donor Tissue in Subjects With Epidermolysis Bullosa


N/A
N/A
25 Years
Not Enrolling
Both
Epidermolysis Bullosa

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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 MinnesotaMinneapolis, Minnesota  55455