Allogeneic Hematopoietic Stem Cell Transplant For Epidermolysis Bullosa

December 3, 2017 updated by: Masonic Cancer Center, University of Minnesota

Allogeneic Hematopoietic Cell Transplantation to Correct the Biochemical Defect and Create Tolerance to Donor Tissue in Subjects With Epidermolysis Bullosa

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

7

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 25 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Epidermolysis Bullosa (EB) Patients
Epidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant.
Drug: busulfan
Day -9 through Day -6: 1.1 mg/kg if < 12 kg IV every 6 hours; 0.8 mg/kg if > 12 kg.
Other Names:
  • Bulsulfex
Drug: cyclophosphamide
Day -5 through Day -2: 50 mg/kg IV over 120 min.
Other Names:
  • Cytoxan
Drug: fludarabine phosphate
Day -5 through Day -3: 25 mg/m2 IV over 60 min.
Other Names:
  • Fludara
  • Fludarabine
Procedure: hematopoietic bone marrow transplantation
allogeneic bone marrow, peripheral stem cell or umbilical cord blood transplantation
Other Names:
  • Bone marrow transplant

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients With Detectable Collagen Type VII
Time Frame: Day 100 Post Transplant
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.
Day 100 Post Transplant

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients With >70% Donor Chimerism
Time Frame: Days 21, 100, 180, 365 and 730 Post Transplant
Number of patients with donor chimerism - percentage of donor cells in the patient via the peripheral blood or bone marrow.
Days 21, 100, 180, 365 and 730 Post Transplant
Number of Patients With Transplant-Related Mortality
Time Frame: Day 180 Post Transplant
Number of patients who died due to complications of the transplant (includes all deaths without previous relapse or progression).
Day 180 Post Transplant
Number of Patients With Platelet Engraftment
Time Frame: Day 180 Post Transplant
Number of patients with a platelet count >5 x 10^10 cells/liter for 3 consecutive measurements.
Day 180 Post Transplant
Number of Patients With Acute Graft-Versus-Host Disease (GVHD)
Time Frame: Day 100 Post Transplant
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.
Day 100 Post Transplant
Number of Patients With Chronic Graft-Versus-Host Disease (cGVHD)
Time Frame: Day 365 Post Transplant
Number of patients with cGVHD; a severe long-term complication created by infusion of donor cells into a foreign host.
Day 365 Post Transplant
Overall Survival
Time Frame: 1 year and 2 years Post Transplant
Survival is defined as the number of patients that were alive post transplant.
1 year and 2 years Post Transplant
Number of Patients With Donor Derived Cells in Skin
Time Frame: Day 90 Post Transplant
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).
Day 90 Post Transplant
Number of Patients With Resistance to Blister Formation
Time Frame: Month 1 through Month 24 Inclusive
Resistance to Blister Formation demonstrated by response to negative pressure.
Month 1 through Month 24 Inclusive
Number of Patients With Neutrophil Engraftment
Time Frame: Day 42 Post Transplant
Number of patients with an absolute neutrophil count >5 x 10^8 cells/liter for 3 consecutive days.
Day 42 Post Transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Masonic Cancer Center, University of Minnesota

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2007

Primary Completion (Actual)

August 1, 2011

Study Completion (Actual)

August 1, 2011

Study Registration Dates

First Submitted

May 23, 2007

First Submitted That Met QC Criteria

May 23, 2007

First Posted (Estimate)

May 24, 2007

Study Record Updates

Last Update Posted (Actual)

December 28, 2017

Last Update Submitted That Met QC Criteria

December 3, 2017

Last Verified

December 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MT2006-15
  • CDR0000546620 (Other Identifier: PDQ)
  • UMN-0702M01504 (Other Identifier: IRB, University of Minnesota)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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