Allogeneic Hematopoietic Stem Cell Transplant For Epidermolysis Bullosa

Masonic Cancer Center, University of Minnesota7 enrolled

Overview

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.

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

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Epidermolysis Bullosa

Interventions

busulfanDRUG

Day -9 through Day -6: 1.1 mg/kg if \< 12 kg IV every 6 hours; 0.8 mg/kg if \> 12 kg.

cyclophosphamideDRUG

Day -5 through Day -2: 50 mg/kg IV over 120 min.

fludarabine phosphateDRUG

Day -5 through Day -3: 25 mg/m2 IV over 60 min.

Eligibility

Sex: ALLMax age: 25 Years

Medical Language ↔ Plain English

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

Locations (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, United States

Outcomes

Primary Outcomes

Number of Patients With Detectable Collagen Type VII

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.

Time frame: Day 100 Post Transplant

Secondary Outcomes

Number of Patients With >70% Donor Chimerism

Number of patients with donor chimerism - percentage of donor cells in the patient via the peripheral blood or bone marrow.

Time frame: Days 21, 100, 180, 365 and 730 Post Transplant

Number of Patients With Transplant-Related Mortality

Number of patients who died due to complications of the transplant (includes all deaths without previous relapse or progression).

Time frame: Day 180 Post Transplant

Number of Patients With Platelet Engraftment

Number of patients with a platelet count \>5 x 10\^10 cells/liter for 3 consecutive measurements.

Time frame: Day 180 Post Transplant

Number of Patients With Acute Graft-Versus-Host Disease (GVHD)

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.

Time frame: Day 100 Post Transplant

Number of Patients With Chronic Graft-Versus-Host Disease (cGVHD)

Number of patients with cGVHD; a severe long-term complication created by infusion of donor cells into a foreign host.

Time frame: Day 365 Post Transplant

Overall Survival

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.