Phase 2 N=32 Treatment

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

Epidermolysis Bullosa

Bottom Line

View on ClinicalTrials.gov: NCT01033552 ↗

Enrolled (actual)

Serious AEs

100.0%

Results posted

Apr 2024

Primary outcome: Primary: Percentage of Participants With Event-free Survival — 67; 80; 50; 29 Percentage of participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Cyclophosphamide (Drug); Fludarabine (Drug); Anti-thymocyte globulin (Drug); Myeloablative Busulfan (Drug); Mesenchymal stem cell transplantation (Procedure); Total body irradiation (Radiation); Bone marrow or umbilical cord blood (UCG) stem cell transplantation (Procedure)
Age: Pediatric, Adult
Sex: All
Sponsor: Masonic Cancer Center, University of Minnesota
Primary completion: Aug 2021

Outcome Measures

Outcome	Result	p-value
PRIMARY Percentage of Participants With Event-free Survival	67; 80; 50; 29; 44; 80	—
SECONDARY Percentage of Participants Transplant-related Mortality (TRM)	43; 19; 50; 86	—
SECONDARY Average Biochemical Improvement	29; 31; 0; 0	—
SECONDARY Measure Patients Quality of Life Using a Questionnaire	43; 17; 1; 37; 68	—
SECONDARY Durability of HSC Donor Engraftment in the Skin	11; 7; 0; 9	—
SECONDARY Probability of Survival	71; 81; 50; 29	—
SECONDARY Percentage of Participants Who Experienced Acute GVHD	14; 19; 0; 29	—

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.

Eligibility 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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01033552). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.