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Stem Cell Transplant for Epidermolysis Bullosa

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2016 by Masonic Cancer Center, University of Minnesota
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota Identifier:
First received: December 14, 2009
Last updated: May 26, 2016
Last verified: May 2016
This is an open-label, single institution, phase II study in patients with epidermolysis bullosa (EB). The underlying hypothesis is that the infusion of bone marrow or umbilical cord blood from a healthy unaffected donor will correct the collagen, laminin, integrin, or plakin deficiency and reduce the skin fragility characteristic of severe forms of EB. A secondary hypothesis is that mesenchymal stem cells from a healthy donor will enhance the safety and efficacy of the allogeneic hematopoietic stem cell transplant as well as serve as a source of renewable cells for the treatment of focal areas of residual blistering.

Condition Intervention Phase
Epidermolysis Bullosa
Drug: Cyclophosphamide
Drug: Fludarabine
Drug: Anti-thymocyte globulin
Drug: Cyclosporine A
Drug: Mycophenolate mofetil
Procedure: Mesenchymal stem cell transplantation
Radiation: Total body irradiation
Procedure: Bone marrow or umbilical cord blood (UCG) stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Biochemical Correction of Severe Epidermolysis Bullosa by Allogeneic Stem Cell Transplantation

Resource links provided by NLM:

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

Primary Outcome Measures:
  • Event-free survival [ Time Frame: 1 year and 2 Years Post-transplant ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of transplant-related mortality (TRM) [ Time Frame: 180 Days Post Transplant ] [ Designated as safety issue: Yes ]
  • Pattern of biochemical improvement measured by increase in protein expression (collagen, laminin, integrin or plakin) [ Time Frame: Through 1 Year Post-Transplant ] [ Designated as safety issue: No ]
  • Quality of Life [ Time Frame: Pretreatment, Day 365 and Day 730 ] [ Designated as safety issue: No ]

Estimated Enrollment: 75
Study Start Date: January 2010
Estimated Study Completion Date: October 2019
Estimated Primary Completion Date: October 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Transplant in Epidermolysis Bullosa Drug: Cyclophosphamide
Cyclophosphamide 50 mg/kg/day IV over 2 hours x 1 day, total dose 50 mg/kg will be administered on Day -6.
Other Name: Cytoxan
Drug: Fludarabine
40 mg/m^2/day intravenously on Days -5, -4, -3 and -2.
Other Name: Fludara
Drug: Anti-thymocyte globulin
30 mg/kg on Days -4, -3 and -2.
Other Name: ATG
Drug: Cyclosporine A
Days -3 to 100+ to maintain a level of >200 ng/ml; initial dose 2.5 mg/kg over 2 hours every 8-12 hours for children.
Other Name: CSA
Drug: Mycophenolate mofetil
15 mg/kg intravenous twice per day on days -3 through 30.
Other Name: CellCept(R)
Procedure: Mesenchymal stem cell transplantation
infused via intravenous drip on Day 0
Other Name: MSCT
Radiation: Total body irradiation
300 cGY on Day -1 administered in a single fraction at a dose rate of 10-19 cGy/minute prescribed to the midplane of the patient at the level of the umbilicus.
Procedure: Bone marrow or umbilical cord blood (UCG) stem cell transplantation
Bone marrow or UCB products will be infused as soon as the product arrives and within 30 minutes. The product is infused via IV drip.
Other Name: UCBSCT

Detailed Description:

The primary objective of this study is to estimate the event-free survival rate by 1 year post-transplant with an event defined as a death or failure to have a demonstrable increase in collagen, laminin, integrin, keratin or plakin deposition by 1 year post-transplant or other biochemical, structual or physical measure of improvement.

The secondary objectives of this study are to i) determine the incidence of transplant-related mortality (TRM) at 180 days; ii) describe the pattern of biochemical improvement as measured by an increase in protein expression (collagen, laminin, integrin, keratin or plakin) and related structural and physical changes; iii) describe health quality of life at day 365 and 730 as compared to pretreatment results; iv) describe the pattern and durability of HSC and third party MSC engraftment in the skin; v) determine the probability of survival at 1 year.

Patients with severe epidermolysis bullosa will be screened to meet the eligibility requirements, related or unrelated donor marrow or UCB will be infused, and subjects will be followed for a minimum of 5 years after stem cell transplant. A target accrual of 75 subjects over 5 years will be recruited to the study.


Ages Eligible for Study:   up to 25 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diagnosis of severe form of epidermolysis bullosa (EB) characterized by collagen, laminin, integrin, keratin or plakin deficiency. Assessment criteria for severe EB:

    • Severe blistering disease requiring dressings on >50% of the body surface area
    • Documented collagen, laminin, integrin, keratin or plakin deficiency (by immunofluorescence staining with protein specific antibodies or Western blotting and by mutation analysis)
    • Poor performance status as a result of EB (Lansky or Karnofsky <50%)
  • Adequate Organ Function Criteria

    • 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
    • Pulmonary: oxygen saturation >92%
    • Cardiac: left ventricular ejection fraction ≥ 45%, normal electrocardiogram (EKG) or approved by Cardiology for transplant.
    • Performance status: ≥ 50% Lansky; ≥ 50% Karnofsky
  • Available Healthy HSC Donor (order of preference)

    • Related Donor (marrow or UCB)

      • HLA-A, B, C, DRB1 genotypic identical (sibling) donor
      • HLA-A, B, C, DRB1 phenotypic identical donor
      • 7/8 HLA matched donor at HLA-A, B, C, DRB1
    • Unrelated Donor

      • Marrow

        • HLA-A, B, C, DRB1 phenotypic identical donor
        • 7/8 HLA matched donor at HLA-A, B, C, DRB1
        • UCB
        • HLA-A, B (antigen level) and DRB1 (allele level) matched donor
        • 5/6 HLA matched donor at HLA-A, B, DRB1
        • 4/6 HLA matched donor at HLA-A, B, DRB1
  • Voluntary written consent

Exclusion Criteria:

  • Active systemic infection at time of transplantation (including active infection with Aspergillus or other mold within 30 days).
  • History of human immunodeficiency virus (HIV) infection
  • Prior transplantation with donor skin
  • Evidence of squamous cell carcinoma
  • Donor has EB
  • Pregnancy or breast feeding. Females of child-bearing age must have a documented negative pregnancy test and agree to use contraception as a condition for enrollment.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01033552

Contact: Patricia Kleinke, RN 612-273-0857

United States, Minnesota
University of Minnesota Masonic Cancer Center and Medical Center Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Patricia Kleinke, RN    612-273-0857   
Principal Investigator: John E Wagner, MD         
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Principal Investigator: Jakub Tolar, MD, PhD Masonic Cancer Center, University of Minnesota
  More Information

Responsible Party: Masonic Cancer Center, University of Minnesota Identifier: NCT01033552     History of Changes
Other Study ID Numbers: MT2009-09  0911M74035 
Study First Received: December 14, 2009
Last Updated: May 26, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Epidermolysis Bullosa
Skin Abnormalities
Congenital Abnormalities
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases
Skin Diseases, Vesiculobullous
Antilymphocyte Serum
Mycophenolate mofetil
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Enzyme Inhibitors
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Calcineurin Inhibitors
Antibiotics, Antineoplastic processed this record on October 27, 2016