Clinical trial NCT00478244: Allogeneic Hematopoietic Stem Cell Transplant For Epidermolysis Bullosa
Official title: Allogeneic Hematopoietic Cell Transplantation to Correct the Biochemical Defect and Create Tolerance to Donor Tissue in Subjects With Epidermolysis Bullosa
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Epidermolysis Bullosa
Keywords: epidermolysis bullosa
dystrophic epidermolysis bullosa
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2007-05-24
Enrollment: 7
Sex: ALL
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Number of Patients With Detectable Collagen Type VII
timeFrame: Day 100 Post Transplant
Secondary outcomes:
measure: Number of Patients With >70% Donor Chimerism
timeFrame: Days 21, 100, 180, 365 and 730 Post Transplant
measure: Number of Patients With Transplant-Related Mortality
timeFrame: Day 180 Post Transplant
measure: Number of Patients With Platelet Engraftment
timeFrame: Day 180 Post Transplant
measure: Number of Patients With Acute Graft-Versus-Host Disease (GVHD)
timeFrame: Day 100 Post Transplant
measure: Number of Patients With Chronic Graft-Versus-Host Disease (cGVHD)
timeFrame: Day 365 Post Transplant
measure: Overall Survival
timeFrame: 1 year and 2 years Post Transplant
measure: Number of Patients With Donor Derived Cells in Skin
timeFrame: Day 90 Post Transplant
measure: Number of Patients With Resistance to Blister Formation
timeFrame: Month 1 through Month 24 Inclusive
measure: Number of Patients With Neutrophil Engraftment
timeFrame: Day 42 Post Transplant
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center, University of Minnesota
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: John E. Wagner, MD
role: STUDY_CHAIR
References:
citation: Wagner JE, Ishida-Yamamoto A, McGrath JA, Hordinsky M, Keene DR, Woodley DT, Chen M, Riddle MJ, Osborn MJ, Lund T, Dolan M, Blazar BR, Tolar J. Bone marrow transplantation for recessive dystrophic epidermolysis bullosa. N Engl J Med. 2010 Aug 12;363(7):629-39. doi: 10.1056/NEJMoa0910501.