Allogeneic Hematopoietic Stem Cell Transplant

For Epidermolysis Bullosa

This study is currently recruiting participants.
Verified by Masonic Cancer Center, University of Minnesota, July 2010
First Received: May 23, 2007 Last Updated: July 29, 2010 History of
Changes

Masonic Cancer Center, University of

Sponsor:
Minnesota

Masonic Cancer Center, University of

Information provided by:
Minnesota

ClinicalTrials.gov
Identifier:
NCT00478244

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: Allocation: Non-Randomized

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:

Genetics Home Reference related topics: dystrophic epidermolysis bullosa

epidermolysis bullosa simplex epidermolysis bullosa with pyloric atresia
junctional epidermolysis bullosa
MedlinePlus related topics: Bone Marrow Transplantation
Drug Information available for: Cyclophosphamide Busulfan Fludarabine
Fludarabine monophosphate
U.S. FDA Resources

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

Minnesota:

Primary Outcome Measures:

• Incidence of detectable collagen type VII [ Time Frame: Days 21, 60,
100, 180, 365 and 730 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

• Incidence of transplant-related mortality at day 180 [ Time Frame: Day
180 ] [ Designated as safety issue: Yes ]
• Incidence of chimerism [ Time Frame: Days 21, 60, 100, 180, 365 and
730 ] [ Designated as safety issue: No ]
• Incidence of platelet recovery [ Time Frame: Day 180 ]
[ Designated as safety issue: No ]
• Incidence of acute graft-versus-host disease (GVHD) [ Time Frame: Day
100 ] [ Designated as safety issue: No ]
• Incidence of chronic graft-versus-host disease (GVHD) [ Time Frame: 1
year ] [ Designated as safety issue: No ]
• Probability of overall survival and disease-free survival [ Time Frame: 1
year and 2 years ] [ Designated as safety issue: No ]
• Incidence of donor derived cells in skin [ Time Frame: Day 90 ]
[ Designated as safety issue: No ]
• Resistance to blister formation [ Time Frame: Days 21, 60, 100, 180, 365
and 730 ] [ Designated as safety issue: No ]
• Incidence of neutrophil recovery [ Time Frame: Day 42 ]
[ Designated as safety issue: No ]

Estimated Enrollment: 30

Study Start Date: April 2007

Estimated Study Completion Date: May 2017

Estimated Primary Completion Date: May 2012 (Final data collection date for
primary outcome measure)

Arms Assigned Interventions

Epidermolysis Bullosa (EB) Patients: Drug: busulfan
Experimental Day -9 through Day -6: 1.1 mg/kg if <
Epidermolysis bullosa patients treated 12 kg IV every 6 hours; 0.8 mg/kg if
per study regimen with chemotherapy and > 12 kg.
stem cell transplant. Other Name: Bulsulfex
Interventions: Drug: cyclophosphamide
Day -5 through Day -2: 50 mg/kg IV
• Drug: busulfan over 120 min.
• Drug: cyclophosphamide Other Name: Cytoxan
• Drug: fludarabine phosphate Drug: fludarabine phosphate
Day -5 through Day -3: 25 mg/m2 IV
• Procedure: hematopoietic bone over 60 min.
marrow transplantation 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)
o Documented collagen type VII deficiency by:
 Antigenic mapping (LH7.2 antibody)
 Ultrastructure analysis of anchoring fibrils
 DNA mutation analysis
• Lansky performance status 60-100%
• Adequate organ function
• Healthy related hematopoietic stem cell donor available and meeting 1 of
the following criteria:
o HLA-A, B, DRB1-identical sibling bone marrow and/or umbilical
cord blood donor (first priority)
o HLA-A, B, DRB1-matched or partially matched related donor
(second priority)
o Donor may be a carrier but must be unaffected by EB
o 8/8 HLA A, B, C, DRB1 allele level matched unrelated marrow
donor (third priority)
o 7/8 HLA-A, B, C, DRB1 allele levelmatched 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
Asperfillus 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

Contacts
Contact: Timothy 612-273- tkrepsk1@fairview.or
Krepski 2800 g

Locations

United States, Minnesota

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

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database

No publications provided by Masonic Cancer Center, University of Minnesota

Additional publications automatically indexed to this study by National Clinical

Trials Identifier (NCT ID):
Wagner JE, Ishida-Yamamoto A, McGrath JA, Hordinsky M, Keene DR, 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.

Responsible Party: Masonic Cancer Center, Universityof Minnesota

( John Wagner, M.D. )
ClinicalTrials.gov NCT00478244 History of Changes
Identifier:
Other Study ID Numbers: UMN-MT2006-15, CDR0000546620, UMN-
0702M01504
Study First Received: May 23, 2007
Last Updated: July 29, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Masonic Cancer Center, University of Minnesota:

epidermolysis bullosa
dystrophic epidermolysis bullosa

Additional relevant MeSH terms:

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

ClinicalTrials.gov processed this record on December 21, 2010

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