TerminatedNCT00478244Updated Dec 28, 2017Results posted

Allogeneic Hematopoietic Stem Cell Transplant For Epidermolysis Bullosa

An interventional study of busulfan and cyclophosphamide in Epidermolysis Bullosa, sponsored by Masonic Cancer Center, University of Minnesota. Terminated at 1 site in United States. Open to participants aged Up to 25 Years. Per ClinicalTrials.gov, last updated 2017-12-28.

Sponsored by Masonic Cancer Center, University of Minnesota · Not applicable, Interventional, and Treatment

Why this study was terminated

Competing studies

Phase: Not applicable
Study type: Interventional
Enrollment: 7
Allocation: Not applicable
Ages: Up to 25 Years
Sex: All

Study 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.

Read the 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

Conditions studied

Epidermolysis Bullosa

Browse trials for

Epidermolysis Bullosa 126

Keywords

epidermolysis bullosa
dystrophic epidermolysis bullosa

In context

Epidermolysis Bullosa

126 studies on the registry are indexed under Epidermolysis Bullosa; 23 are open to participants now.

This study's enrollment of 7 is below the median of 11 across 95 interventional studies indexed under Epidermolysis Bullosa.

Browse Epidermolysis Bullosa studies →

Lead sponsor

Masonic Cancer Center, University of Minnesota is the lead sponsor of 284 studies on the registry; 34 are open to participants now.

Of its 39 completed or terminated interventional studies of FDA-regulated products, 28 (72%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: Up to 25 Years
Sexes eligible: All
Accepts healthy volunteers: No

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

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

Study design

Phase: Not applicable
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 7 participants (actual)

Study arms

Experimental
Epidermolysis Bullosa (EB) Patients
Epidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant.
Drug: busulfan · Drug: cyclophosphamide · Drug: fludarabine phosphate · Procedure: hematopoietic bone marrow transplantation

Interventions

Drugbusulfan
Day -9 through Day -6: 1.1 mg/kg if \< 12 kg IV every 6 hours; 0.8 mg/kg if \> 12 kg.
Also known as: Bulsulfex
Drugcyclophosphamide
Day -5 through Day -2: 50 mg/kg IV over 120 min.
Also known as: Cytoxan
Drugfludarabine phosphate
Day -5 through Day -3: 25 mg/m2 IV over 60 min.
Also known as: Fludarabine, Fludara
Procedurehematopoietic bone marrow transplantation
allogeneic bone marrow, peripheral stem cell or umbilical cord blood transplantation
Also known as: Bone marrow transplant

What researchers measure

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
Survival is defined as the number of patients that were alive post transplant.
Time frame: 1 year and 2 years Post Transplant
Number of Patients With Donor Derived Cells in Skin
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).
Time frame: Day 90 Post Transplant
Number of Patients With Resistance to Blister Formation
Resistance to Blister Formation demonstrated by response to negative pressure.
Time frame: Month 1 through Month 24 Inclusive
Number of Patients With Neutrophil Engraftment
Number of patients with an absolute neutrophil count \>5 x 10\^8 cells/liter for 3 consecutive days.
Time frame: Day 42 Post Transplant

Results

Posted Feb 11, 2013

Participant flow

Participant flow — Overall Study
Milestone	Epidermolysis Bullosa (EB) Patients
Started	7
Completed	6
Not completed	1
Withdrew: Did not receive transplant	1

Outcome measures

SecondaryNumber 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
Reported as:: Number · participants

Number of Patients With >70% Donor Chimerism
participants	Evaluable Patients
Day 21	6
Day 100	5
Day 180	5
Day 365	5
Day 730	5

SecondaryNumber 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
Reported as:: Number · participants

Number of Patients With Transplant-Related Mortality
participants	Evaluable Patients
Number of Patients With Transplant-Related Mortality	0

SecondaryNumber 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
Reported as:: Number · participants

Number of Patients With Platelet Engraftment
participants	Evaluable Patients
Number of Patients With Platelet Engraftment	5

SecondaryNumber 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
Reported as:: Number · participants

Number of Patients With Acute Graft-Versus-Host Disease (GVHD)
participants	Evaluable Patients
Number of Patients With Acute Graft-Versus-Host Disease (GVHD)	1

SecondaryNumber 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
Reported as:: Number · participants

Number of Patients With Chronic Graft-Versus-Host Disease (cGVHD)
participants	Evaluable Patients
Number of Patients With Chronic Graft-Versus-Host Disease (cGVHD)	0

SecondaryOverall Survival

Survival is defined as the number of patients that were alive post transplant.

Time frame:: 1 year and 2 years Post Transplant
Reported as:: Number · participants

Overall Survival
participants	Evaluable Patients
1 Year Post Transplant	5
2 Years Post Transplant	5

SecondaryNumber of Patients With Donor Derived Cells in Skin

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).

Time frame:: Day 90 Post Transplant
Reported as:: Number · participants

Number of Patients With Donor Derived Cells in Skin
participants	Evaluable Patients
Number of Patients With Donor Derived Cells in Skin	6

SecondaryNumber of Patients With Resistance to Blister Formation

Resistance to Blister Formation demonstrated by response to negative pressure.

Time frame:: Month 1 through Month 24 Inclusive
Reported as:: Number · participants

Number of Patients With Resistance to Blister Formation
participants	Evaluable Patients
Number of Patients With Resistance to Blister Formation	2

SecondaryNumber of Patients With Neutrophil Engraftment

Number of patients with an absolute neutrophil count \>5 x 10\^8 cells/liter for 3 consecutive days.

Time frame:: Day 42 Post Transplant
Reported as:: Number · participants

Number of Patients With Neutrophil Engraftment
participants	Evaluable Patients
Number of Patients With Neutrophil Engraftment	6

PrimaryNumber 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
Reported as:: Number · participants

Number of Patients With Detectable Collagen Type VII
participants	Evaluable Patients
Number of Patients With Detectable Collagen Type VII	5

Adverse events

Collected over All subjects were monitored continuously and only serious unexpected and selected serious adverse experiences were collected during the first 100 days after cell infusion.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Epidermolysis Bullosa (EB) Patients	—	6/7 (85.7%)	0/7 (0%)

Most frequent serious events

Most frequent serious events
Event	Epidermolysis Bullosa (EB) Patients
Bacterial infectionInfections and infestations	6/7
HyperbilirubinemiaMetabolism and nutrition disorders	4/7
Fungal infectionInfections and infestations	2/7
Renal insufficiencyRenal and urinary disorders	2/7
Acute respiratory distress syndromeRespiratory, thoracic and mediastinal disorders	1/7
DeathGeneral disorders	1/7
Grade IV skin toxicitySkin and subcutaneous tissue disorders	1/7
Graft failureBlood and lymphatic system disorders	1/7
Hemorrhagic cystitisRenal and urinary disorders	1/7
Viral infectionInfections and infestations	1/7

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Epidermolysis Bullosa (EB) Patients
<=18 years	7
Between 18 and 65 years	0
>=65 years	0

Age, Continuous
Age, Continuous(years)	Epidermolysis Bullosa (EB) Patients
Mean	6.0 ± 4.5

Sex: Female, Male
Sex: Female, Male(Participants)	Epidermolysis Bullosa (EB) Patients
Female	4
Male	3

Region of Enrollment
Region of Enrollment(participants)	Epidermolysis Bullosa (EB) Patients
United States	7

Study locations

1 site

Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota 55455, United States

References and documents

Publications

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. Erratum In: N Engl J Med. 2010 Sep 30;363(14):1383. Woodley, David T [added]; Chen, Mei [added]. PubMed 20818854 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Dec 28, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00478244
Lead sponsor: Masonic Cancer Center, University of Minnesota
Responsible party: Sponsor
First posted: May 24, 2007
Start date: Apr 2007
Primary completion: Aug 2011
Completion: Aug 2011
Results posted: Feb 11, 2013
Last update: Dec 28, 2017

Study contacts

John E. Wagner, MD

study chair · Masonic Cancer Center, University of Minnesota

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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