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Allogeneic Hematopoietic Stem Cell Transplant For Epidermolysis Bullosa

Primary Purpose

Epidermolysis Bullosa

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
busulfan
cyclophosphamide
fludarabine phosphate
hematopoietic bone marrow transplantation
Sponsored by
Masonic Cancer Center, University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Epidermolysis Bullosa focused on measuring epidermolysis bullosa, dystrophic epidermolysis bullosa

Eligibility Criteria

undefined - 25 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Masonic Cancer Center, University of Minnesota

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Epidermolysis Bullosa (EB) Patients

Arm Description

Epidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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).
Number of Patients With Platelet Engraftment
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)
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)
Number of patients with cGVHD; a severe long-term complication created by infusion of donor cells into a foreign host.
Overall Survival
Survival is defined as the number of patients that were alive 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).
Number of Patients With Resistance to Blister Formation
Resistance to Blister Formation demonstrated by response to negative pressure.
Number of Patients With Neutrophil Engraftment
Number of patients with an absolute neutrophil count >5 x 10^8 cells/liter for 3 consecutive days.

Full Information

First Posted
May 23, 2007
Last Updated
December 3, 2017
Sponsor
Masonic Cancer Center, University of Minnesota
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1. Study Identification

Unique Protocol Identification Number
NCT00478244
Brief Title
Allogeneic Hematopoietic Stem Cell Transplant For Epidermolysis Bullosa
Official Title
Allogeneic Hematopoietic Cell Transplantation to Correct the Biochemical Defect and Create Tolerance to Donor Tissue in Subjects With Epidermolysis Bullosa
Study Type
Interventional

2. Study Status

Record Verification Date
December 2017
Overall Recruitment Status
Terminated
Why Stopped
Competing studies
Study Start Date
April 2007 (undefined)
Primary Completion Date
August 2011 (Actual)
Study Completion Date
August 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Masonic Cancer Center, University of Minnesota

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epidermolysis Bullosa
Keywords
epidermolysis bullosa, dystrophic epidermolysis bullosa

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Epidermolysis Bullosa (EB) Patients
Arm Type
Experimental
Arm Description
Epidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant.
Intervention Type
Drug
Intervention Name(s)
busulfan
Other Intervention Name(s)
Bulsulfex
Intervention Description
Day -9 through Day -6: 1.1 mg/kg if < 12 kg IV every 6 hours; 0.8 mg/kg if > 12 kg.
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Other Intervention Name(s)
Cytoxan
Intervention Description
Day -5 through Day -2: 50 mg/kg IV over 120 min.
Intervention Type
Drug
Intervention Name(s)
fludarabine phosphate
Other Intervention Name(s)
Fludarabine, Fludara
Intervention Description
Day -5 through Day -3: 25 mg/m2 IV over 60 min.
Intervention Type
Procedure
Intervention Name(s)
hematopoietic bone marrow transplantation
Other Intervention Name(s)
Bone marrow transplant
Intervention Description
allogeneic bone marrow, peripheral stem cell or umbilical cord blood transplantation
Primary Outcome Measure Information:
Title
Number of Patients With Detectable Collagen Type VII
Description
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 Outcome Measure Information:
Title
Number of Patients With >70% Donor Chimerism
Description
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
Title
Number of Patients With Transplant-Related Mortality
Description
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
Title
Number of Patients With Platelet Engraftment
Description
Number of patients with a platelet count >5 x 10^10 cells/liter for 3 consecutive measurements.
Time Frame
Day 180 Post Transplant
Title
Number of Patients With Acute Graft-Versus-Host Disease (GVHD)
Description
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
Title
Number of Patients With Chronic Graft-Versus-Host Disease (cGVHD)
Description
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
Title
Overall Survival
Description
Survival is defined as the number of patients that were alive post transplant.
Time Frame
1 year and 2 years Post Transplant
Title
Number of Patients With Donor Derived Cells in Skin
Description
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
Title
Number of Patients With Resistance to Blister Formation
Description
Resistance to Blister Formation demonstrated by response to negative pressure.
Time Frame
Month 1 through Month 24 Inclusive
Title
Number of Patients With Neutrophil Engraftment
Description
Number of patients with an absolute neutrophil count >5 x 10^8 cells/liter for 3 consecutive days.
Time Frame
Day 42 Post Transplant

10. Eligibility

Sex
All
Maximum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John E. Wagner, MD
Organizational Affiliation
Masonic Cancer Center, University of Minnesota
Official's Role
Study Chair
Facility Information:
Facility Name
Masonic Cancer Center, University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
20818854
Citation
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].
Results Reference
derived

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Allogeneic Hematopoietic Stem Cell Transplant For Epidermolysis Bullosa

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