Allogeneic Hematopoietic Stem Cell Transplant For Epidermolysis Bullosa

University of Minnesota (UMN)

Status

Terminated

Conditions

Epidermolysis Bullosa

Treatments

Drug: busulfan

Drug: cyclophosphamide

Drug: fludarabine phosphate

Procedure: hematopoietic bone marrow transplantation

Study type

Interventional

Funder types

Other

Identifiers

NCT00478244

MT2006-15

CDR0000546620 (Other Identifier)

UMN-0702M01504 (Other Identifier)

Details and patient eligibility

About

RATIONALE: In animal models, stem cells have been shown to home to the skin and repair the biochemical and structural abnormalities associated with recessive dystrophic epidermolysis bullosa (RDEB) (collagen 7 deficiency).

PURPOSE: To determine the safety and effectiveness of stem cell infusion in the treatment of RDEB.

Full description

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

Enrollment

7 patients

Sex

All

Ages

Under 25 years old

Volunteers

No Healthy Volunteers

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