Biochemical Correction of Severe EB by Allo HSCT and "Off-the-shelf" MSCs
| Status: | Recruiting |
|---|---|
| Conditions: | Skin and Soft Tissue Infections |
| Therapuetic Areas: | Dermatology / Plastic Surgery |
| Healthy: | No |
| Age Range: | Any - 25 |
| Updated: | 9/26/2018 |
| Start Date: | January 2010 |
| End Date: | October 2019 |
| Contact: | Kim Nelson, RN |
| Email: | knelso62@fairview.org |
| Phone: | 612-273-2925 |
MT2009-09: Biochemical Correction of Severe Epidermolysis Bullosa by Allogeneic Stem Cell Transplantation and "Off-the-shelf" Mesenchymal Stem Cells
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.
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.
The primary objective of this study is to estimate the event-free survival rate by 1 year
post-transplant with an event defined as a death or failure to have a demonstrable increase
in collagen, laminin, integrin, keratin or plakin deposition by 1 year post-transplant or
other biochemical, structural or physical measure of improvement.
The secondary objectives of this study are to i) determine the incidence of
transplant-related mortality (TRM) at 180 days; ii) describe the pattern of biochemical
improvement as measured by an increase in protein expression (collagen, laminin, integrin,
keratin or plakin) and related structural and physical changes; iii) describe health quality
of life at day 365 and 730 as compared to pretreatment results; iv) describe the pattern and
durability of HSC and third party MSC engraftment in the skin; v) determine the probability
of survival at 1 year.
Patients with severe epidermolysis bullosa will be screened to meet the eligibility
requirements, related or unrelated donor marrow or UCB will be infused, and subjects will be
followed for a minimum of 5 years after stem cell transplant. A target accrual of 75 subjects
over 5 years will be recruited to the study.
post-transplant with an event defined as a death or failure to have a demonstrable increase
in collagen, laminin, integrin, keratin or plakin deposition by 1 year post-transplant or
other biochemical, structural or physical measure of improvement.
The secondary objectives of this study are to i) determine the incidence of
transplant-related mortality (TRM) at 180 days; ii) describe the pattern of biochemical
improvement as measured by an increase in protein expression (collagen, laminin, integrin,
keratin or plakin) and related structural and physical changes; iii) describe health quality
of life at day 365 and 730 as compared to pretreatment results; iv) describe the pattern and
durability of HSC and third party MSC engraftment in the skin; v) determine the probability
of survival at 1 year.
Patients with severe epidermolysis bullosa will be screened to meet the eligibility
requirements, related or unrelated donor marrow or UCB will be infused, and subjects will be
followed for a minimum of 5 years after stem cell transplant. A target accrual of 75 subjects
over 5 years will be recruited to the study.
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.
We found this trial at
1
site
Minneapolis, Minnesota 55455
Principal Investigator: Jakub Tolar, MD, PhD
Phone: 612-273-2925
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