Allogeneic Hematopoietic Stem Cell Transplant For Epidermolysis Bullosa
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.
Drug: fludarabine phosphate
Procedure: hematopoietic bone marrow transplantation
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Allogeneic Hematopoietic Cell Transplantation to Correct the Biochemical Defect and Create Tolerance to Donor Tissue in Subjects With Epidermolysis Bullosa|
- Number of Patients With Detectable Collagen Type VII [ Time Frame: 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.
- Number of Patients With >70% Donor Chimerism [ Time Frame: 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 Transplant-Related Mortality [ Time Frame: Day 180 Post Transplant ]Number of patients who died due to complications of the transplant (includes all deaths without previous relapse or progression).
- Number of Patients With Platelet Engraftment [ Time Frame: 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 Acute Graft-Versus-Host Disease (GVHD) [ Time Frame: 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 Chronic Graft-Versus-Host Disease (cGVHD) [ Time Frame: Day 365 Post Transplant ]Number of patients with cGVHD; a severe long-term complication created by infusion of donor cells into a foreign host.
- Overall Survival [ Time Frame: 1 year and 2 years Post Transplant ]Survival is defined as the number of patients that were alive post transplant.
- Number of Patients With Donor Derived Cells in Skin [ Time Frame: 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 Resistance to Blister Formation [ Time Frame: Month 1 through Month 24 Inclusive ]Resistance to Blister Formation demonstrated by response to negative pressure.
- Number of Patients With Neutrophil Engraftment [ Time Frame: Day 42 Post Transplant ]Number of patients with an absolute neutrophil count >5 x 10^8 cells/liter for 3 consecutive days.
|Study Start Date:||April 2007|
|Study Completion Date:||August 2011|
|Primary Completion Date:||August 2011 (Final data collection date for primary outcome measure)|
Experimental: Epidermolysis Bullosa (EB) Patients
Epidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant.
Day -9 through Day -6: 1.1 mg/kg if < 12 kg IV every 6 hours; 0.8 mg/kg if > 12 kg.
Other Name: BulsulfexDrug: cyclophosphamide
Day -5 through Day -2: 50 mg/kg IV over 120 min.
Other Name: CytoxanDrug: fludarabine phosphate
Day -5 through Day -3: 25 mg/m2 IV over 60 min.
Other Names:Procedure: hematopoietic bone marrow transplantation
allogeneic bone marrow, peripheral stem cell or umbilical cord blood transplantation
Other Name: Bone marrow transplant
- Estimate the incidence of detectable donor-derived collagen type VII at day 100 in patients with epidermolysis bullosa by donor.
- 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00478244
|United States, Minnesota|
|Masonic Cancer Center, University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|Study Chair:||John E. Wagner, MD||Masonic Cancer Center, University of Minnesota|