Biochemical Correction of Severe EB by Allo HSCT and "Off-the-shelf" MSCs
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ClinicalTrials.gov Identifier: NCT01033552 |
Recruitment Status :
Active, not recruiting
First Posted : December 16, 2009
Last Update Posted : September 29, 2022
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Condition or disease | Intervention/treatment | Phase |
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Epidermolysis Bullosa | Drug: Cyclophosphamide Drug: Fludarabine Drug: Anti-thymocyte globulin Drug: Cyclosporine A Drug: Mycophenolate mofetil Procedure: Mesenchymal stem cell transplantation Radiation: Total body irradiation Procedure: Bone marrow or umbilical cord blood (UCG) stem cell transplantation | Phase 1 Phase 2 |
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.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 32 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | MT2009-09: Biochemical Correction of Severe Epidermolysis Bullosa by Allogeneic Stem Cell Transplantation and "Off-the-shelf" Mesenchymal Stem Cells |
Actual Study Start Date : | January 2010 |
Estimated Primary Completion Date : | November 12, 2022 |
Estimated Study Completion Date : | December 12, 2022 |

Arm | Intervention/treatment |
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Experimental: Transplant in Epidermolysis Bullosa |
Drug: Cyclophosphamide
Cyclophosphamide 50 mg/kg/day IV over 2 hours x 1 day, total dose 50 mg/kg will be administered on Day -6.
Other Name: Cytoxan Drug: Fludarabine 40 mg/m^2/day intravenously on Days -6, -5, -4, -3 and -2.
Other Name: Fludara Drug: Anti-thymocyte globulin 30 mg/kg on Days -4, -3 and -2.
Other Name: ATG Drug: Cyclosporine A Days -3 to 100+ to maintain a level of >200 ng/ml; initial dose 2.5 mg/kg over 2 hours every 8-12 hours for children.
Other Name: CSA Drug: Mycophenolate mofetil 15 mg/kg intravenous twice per day on days -3 through 30.
Other Name: CellCept(R) Procedure: Mesenchymal stem cell transplantation infused via intravenous drip on Day 0
Other Name: MSCT Radiation: Total body irradiation 300 cGY on Day -1 administered in a single fraction at a dose rate of 10-19 cGy/minute prescribed to the midplane of the patient at the level of the umbilicus. Procedure: Bone marrow or umbilical cord blood (UCG) stem cell transplantation Bone marrow or UCB products will be infused as soon as the product arrives and within 30 minutes. The product is infused via IV drip.
Other Name: UCBSCT |
- Event-free survival rate [ Time Frame: 1 year and 2 Years Post-transplant ]Event-free survival rate, with an event defined as death or failure to have a demonstrable increase in collagen, laminin, intergrin, keratin or plakin deposition.
- Transplant-related mortality (TRM) [ Time Frame: 180 Days Post Transplant ]Incidence of transplant-related mortality (TRM)
- Pattern of biochemical improvement [ Time Frame: Through 1 Year Post-Transplant ]Describe pattern of biochemical improvement as measured by an increase in protein expression (collagen, laminin, integrin, keratin, or plakin) and related structural and physical changes
- Measure patients Quality of Life using a questionnaire [ Time Frame: Pretreatment, Day 100, 6 months, 1 and 2 years ]Health quality of life questionnaire or iscorEB as compared to pretreatment results
- Durability of HSC and third party MSC engraftment in the skin [ Time Frame: 100 Days ]Incidence of HSC and third party MSC engraftment in the skin
- Probability of Survival [ Time Frame: 1 Year ]Number of surviving patients one year after engraftment
- Number of participants experiencing Acute GVHD [ Time Frame: 100 Days ]Incidence of acute GCHD

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Ages Eligible for Study: | up to 25 Years (Child, Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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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)
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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.
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Available Healthy HSC Donor (order of preference)
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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
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Unrelated Donor
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Marrow
- HLA-A, B, C, DRB1 phenotypic identical donor
- 7/8 HLA matched donor at HLA-A, B, C, DRB1
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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
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- 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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01033552
United States, Minnesota | |
University of Minnesota Masonic Cancer Center and Medical Center | |
Minneapolis, Minnesota, United States, 55455 |
Principal Investigator: | Jakub Tolar, MD, PhD | Masonic Cancer Center, University of Minnesota |
Responsible Party: | Masonic Cancer Center, University of Minnesota |
ClinicalTrials.gov Identifier: | NCT01033552 |
Other Study ID Numbers: |
MT2009-09 0911M74035 ( Other Identifier: IRB, University of Minnesota ) |
First Posted: | December 16, 2009 Key Record Dates |
Last Update Posted: | September 29, 2022 |
Last Verified: | September 2022 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Epidermolysis Bullosa Skin Abnormalities Congenital Abnormalities Skin Diseases, Genetic Genetic Diseases, Inborn Skin Diseases Skin Diseases, Vesiculobullous Cyclosporine Mycophenolic Acid Cyclophosphamide Fludarabine Cyclosporins Antilymphocyte Serum Immunosuppressive Agents Immunologic Factors |
Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Enzyme Inhibitors Antifungal Agents Anti-Infective Agents Dermatologic Agents Calcineurin Inhibitors Antibiotics, Antineoplastic Antibiotics, Antitubercular Antitubercular Agents |