Conditions: Epidermolysis Bullosa
Keywords: epidermolysis bullosa dystrophic epidermolysis bullosa
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 7
Healthy volunteers: no

Brief summary:
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.

Detailed 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

Arms:
arm 1: Epidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant.

Interventions: intervention 1: busulfan intervention 2: cyclophosphamide intervention 3: fludarabine phosphate intervention 4: hematopoietic bone marrow transplantation
Intervention descriptions: intervention 1: Day -9 through Day -6: 1.1 mg/kg if \< 12 kg IV every 6 hours; 0.8 mg/kg if \> 12 kg. intervention 2: Day -5 through Day -2: 50 mg/kg IV over 120 min. intervention 3: Day -5 through Day -3: 25 mg/m2 IV over 60 min. intervention 4: allogeneic bone marrow, peripheral stem cell or umbilical cord blood transplantation

Protocol document: