Allogeneic Hematopoietic Stem Cell Transplant For Epidermolysis Bullosa

NCT ID: NCT00478244

Last Updated: 2017-12-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-04-30
• Study Completion Date: 2011-08-31

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

Conditions

Epidermolysis Bullosa

Keywords

epidermolysis bullosa; dystrophic epidermolysis bullosa

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Epidermolysis Bullosa (EB) Patients

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

Group Type: EXPERIMENTAL

busulfan

Intervention Type: DRUG

Day -9 through Day -6: 1.1 mg/kg if \< 12 kg IV every 6 hours; 0.8 mg/kg if \> 12 kg.

cyclophosphamide

Intervention Type: DRUG

Day -5 through Day -2: 50 mg/kg IV over 120 min.

fludarabine phosphate

Intervention Type: DRUG

Day -5 through Day -3: 25 mg/m2 IV over 60 min.

hematopoietic bone marrow transplantation

Intervention Type: PROCEDURE

allogeneic bone marrow, peripheral stem cell or umbilical cord blood transplantation

Interventions

busulfan

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

cyclophosphamide

Day -5 through Day -2: 50 mg/kg IV over 120 min.

Intervention Type: DRUG

fludarabine phosphate

Day -5 through Day -3: 25 mg/m2 IV over 60 min.

Intervention Type: DRUG

hematopoietic bone marrow transplantation

allogeneic bone marrow, peripheral stem cell or umbilical cord blood transplantation

Intervention Type: PROCEDURE

Other Intervention Names

Bulsulfex; Cytoxan; Fludarabine; Fludara; Bone marrow transplant

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

• Maximum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John E. Wagner, MD

Role: STUDY_CHAIR

Masonic Cancer Center, University of Minnesota

Locations

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 20818854 (View on PubMed)

Other Identifiers

CDR0000546620

Identifier Type: OTHER

Identifier Source: secondary_id

UMN-0702M01504

Identifier Type: OTHER

Identifier Source: secondary_id

MT2006-15

Identifier Type: -

Identifier Source: org_study_id