Biochemical Correction of Severe EB by Allo HSCT and "Off-the-shelf" MSCs

• Status: Recruiting
• Trial end date: 2021-10-01
• Target enrollment: 0
• Participant gender: All

Summary

This is an open-label, single institution, phase II study in patients with epidermolysis bullosa (EB). The underlying hypothesis is that the infusion of bone marrow or umbilical cord blood from a healthy unaffected donor will correct the collagen, laminin, integrin, or plakin deficiency and reduce the skin fragility characteristic of severe forms of EB. A secondary hypothesis is that mesenchymal stem cells from a healthy donor will enhance the safety and efficacy of the allogeneic hematopoietic stem cell transplant as well as serve as a source of renewable cells for the treatment of focal areas of residual blistering.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Masonic Cancer Center, University of Minnesota
• Treatments: Antilymphocyte Serum; Cyclophosphamide; Cyclosporine; Cyclosporins; Fludarabine; Mycophenolate mofetil; Mycophenolic Acid

Criteria

Inclusion Criteria:

• Diagnosis of severe form of epidermolysis bullosa (EB) characterized by collagen, laminin, integrin, keratin or plakin deficiency. Assessment criteria for severe EB:

• Documented collagen, laminin, integrin, keratin or plakin deficiency (by immunofluorescence staining with protein specific antibodies or Western blotting and by mutation analysis)

• Adequate Organ Function Criteria

• Renal: glomerular filtration rate within normal range for age

• Hepatic: bilirubin, aspartate aminotransferase/alanine aminotransferase (AST/ALT), Alkaline phosphatase (ALP) < 5 x upper limit of normal

• Pulmonary: adequate pulmonary function in the opinion of the enrolling investigator

• Cardiac: left ventricular ejection fraction ≥ 45%, normal electrocardiogram (EKG) or approved by Cardiology for transplant.

• Available Healthy HSC Donor (order of preference)

• Related Donor (marrow or UCB)

• HLA-A, B, C, DRB1 genotypic identical (sibling) donor

• HLA-A, B, C, DRB1 phenotypic identical donor

• 7/8 HLA matched donor at HLA-A, B, C, DRB1

• Unrelated Donor

• Marrow

• HLA-A, B, C, DRB1 phenotypic identical donor

• 7/8 HLA matched donor at HLA-A, B, C, DRB1

• UCB

• HLA-A, B (antigen level) and DRB1 (allele level) matched donor

• 5/6 HLA matched donor at HLA-A, B, DRB1

• 4/6 HLA matched donor at HLA-A, B, DRB1

• Voluntary written consent

Absence of Exclusion Criteria:

• Active systemic infection at time of transplantation (including active infection with Aspergillus or other mold within 30 days).

• History of human immunodeficiency virus (HIV) infection

• Evidence of squamous cell carcinoma

• Donor has EB

• Pregnancy females of child-bearing age must have a documented negative pregnancy test and agree to use contraception as a condition for enrollment.