Clinical Trial: Allogeneic Hematopoietic Stem Cell Transplant For Epidermolysis Bullosa

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

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

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 Summary:

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


Sponsor: Masonic Cancer Center, University of Minnesota

Current Primary Outcome: 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.


Original Primary Outcome: Incidence of detectable donor-derived collagen type VII by day 100

Current Secondary Outcome:

  • 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.


Original Secondary Outcome:

  • Incidence of transplant-related mortality at 180 days
  • Incidence of chimerism at 21, 100, 180, 365, and 730 days
  • Incidence of neutrophil recovery at day 42 and platelet recovery at 180 days
  • Incidence of acute graft-versus-host disease (GVHD) at day 100
  • Incidence of chronic GVHD at 1 year
  • Probability of survival and disease-free survival at 1 and 2 years
  • Incidence of donor skin-derived epidermal cell survival 90 days after epidermal cell transplantation


Information By: Masonic Cancer Center, University of Minnesota

Dates:
Date Received: May 23, 2007
Date Started: April 2007
Date Completion:
Last Updated: January 4, 2013
Last Verified: January 2013