Allogeneic Hematopoietic Stem Cell Transplant For Epidermolysis Bullosa

Not Applicable

Terminated

Conditions: Epidermolysis Bullosa

Interventions: Drug: busulfan
Drug: cyclophosphamide
Drug: fludarabine phosphate
Procedure: hematopoietic bone marrow transplantation

Registration Number: NCT00478244

Lead Sponsor: Masonic Cancer Center, University of Minnesota

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

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 7

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Epidermolysis Bullosa (EB) Patients	hematopoietic bone marrow transplantation	Epidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant.
Epidermolysis Bullosa (EB) Patients	busulfan	Epidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant.
Epidermolysis Bullosa (EB) Patients	cyclophosphamide	Epidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant.
Epidermolysis Bullosa (EB) Patients	fludarabine phosphate	Epidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant.

Primary Outcome Measures

Name	Time	Method
Number of Patients With Detectable Collagen Type VII	Day 100 Post Transplant	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.

Secondary Outcome Measures

Name	Time	Method
Number of Patients With Chronic Graft-Versus-Host Disease (cGVHD)	Day 365 Post Transplant	Number of patients with cGVHD; a severe long-term complication created by infusion of donor cells into a foreign host.
Number of Patients With Resistance to Blister Formation	Month 1 through Month 24 Inclusive	Resistance to Blister Formation demonstrated by response to negative pressure.
Number of Patients With >70% Donor Chimerism	Days 21, 100, 180, 365 and 730 Post Transplant	Number of patients with donor chimerism - percentage of donor cells in the patient via the peripheral blood or bone marrow.
Number of Patients With Platelet Engraftment	Day 180 Post Transplant	Number of patients with a platelet count \>5 x 10\^10 cells/liter for 3 consecutive measurements.
Number of Patients With Transplant-Related Mortality	Day 180 Post Transplant	Number of patients who died due to complications of the transplant (includes all deaths without previous relapse or progression).
Overall Survival	1 year and 2 years Post Transplant	Survival is defined as the number of patients that were alive post transplant.
Number of Patients With Acute Graft-Versus-Host Disease (GVHD)	Day 100 Post Transplant	Number of patients with GVHD. Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.
Number of Patients With Donor Derived Cells in Skin	Day 90 Post Transplant	Number of patients who had donor skin chimerism - donor cells in the patient's epidermis (a state in bone marrow transplantation in which bone marrow and host cells exist compatibly without signs of graft-versus-host rejection disease).
Number of Patients With Neutrophil Engraftment	Day 42 Post Transplant	Number of patients with an absolute neutrophil count \>5 x 10\^8 cells/liter for 3 consecutive days.