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Allogeneic Hematopoietic Stem Cell Transplant For Epidermolysis Bullosa

This study has been terminated.
(Competing studies)
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00478244
First received: May 23, 2007
Last updated: January 4, 2013
Last verified: January 2013
History of Changes
  Purpose

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.


Condition Intervention
Epidermolysis Bullosa
 Drug: busulfan
Drug: cyclophosphamide
Drug: fludarabine phosphate
Procedure: hematopoietic bone marrow transplantation

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • Number of Patients With Detectable Collagen Type VII [ Time Frame: Day 100 Post Transplant ] [ Designated as safety issue: No ]
    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:
  • Number of Patients With >70% Donor Chimerism [ Time Frame: Days 21, 100, 180, 365 and 730 Post Transplant ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Resistance to Blister Formation demonstrated by response to negative pressure.

  • Number of Patients With Neutrophil Engraftment [ Time Frame: Day 42 Post Transplant ] [ Designated as safety issue: No ]
    Number of patients with an absolute neutrophil count >5 x 10^8 cells/liter for 3 consecutive days.


Enrollment: 7
Study Start Date: April 2007
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Epidermolysis Bullosa (EB) Patients
Epidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant.
 Drug: busulfan
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: Bulsulfex
Drug: cyclophosphamide
Day -5 through Day -2: 50 mg/kg IV over 120 min.
Other Name: Cytoxan
Drug: fludarabine phosphate
Day -5 through Day -3: 25 mg/m2 IV over 60 min.
Other Names:
  • Fludarabine
  • Fludara
Procedure: hematopoietic bone marrow transplantation
allogeneic bone marrow, peripheral stem cell or umbilical cord blood transplantation
Other Name: Bone marrow transplant

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

Ages Eligible for Study:   up to 25 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00478244

Locations
United States, Minnesota
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Study Chair: John E. Wagner, MD Masonic Cancer Center, University of Minnesota
  More Information

No publications provided by Masonic Cancer Center, University of Minnesota

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00478244     History of Changes
Other Study ID Numbers: MT2006-15, CDR0000546620, UMN-0702M01504
Study First Received: May 23, 2007
Results First Received: July 17, 2012
Last Updated: January 4, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Masonic Cancer Center, University of Minnesota:
epidermolysis bullosa
dystrophic epidermolysis bullosa

Additional relevant MeSH terms:
Epidermolysis Bullosa
Skin Abnormalities
Congenital Abnormalities
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases
Skin Diseases, Vesiculobullous
Busulfan
Cyclophosphamide
Fludarabine monophosphate
Fludarabine
Vidarabine
Immunosuppressive Agents
Immunologic Factors
 Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Antirheumatic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on May 22, 2013