Biochemical Correction of Severe EB by Allo HSCT and "Off-the-shelf" MSCs
NCT ID: NCT01033552
Last Updated: 2024-04-03
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE1/PHASE2
32 participants
INTERVENTIONAL
2010-01-31
2021-08-12
Brief Summary
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Detailed Description
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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.
Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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RDEB Mac
Recessive Dystrophic EB (RDEB) - Myeloablative conditioning (MAC) Participants receive Myeloablative Busulfan (targeting AUC 1000 umol/min), Fludarabine 75 mg/m2, and Cyclophosphamide 200 mg/kg
Cyclophosphamide
Cyclophosphamide 50 mg/kg/day IV over 2 hours x 1 day, total dose 50 mg/kg will be administered on Day -6.
Fludarabine
40 mg/m\^2/day intravenously on Days -6, -5, -4, -3 and -2.
Myeloablative Busulfan
Targeting AUC 1000 umol/min
Mesenchymal stem cell transplantation
infused via intravenous drip on Day 0
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.
RDEB RIC
Recessive Dystrophic EB (RDEB) - Reduced Intensity Condition Participants received Fludarabine 500 mg/m2, Cyclosphosphamide 50 mg/kg, equine Anti-thymocyte globulin 90 mg/kg, and low dose total body irradiation (either 200 or 300 cGy)
Cyclophosphamide
Cyclophosphamide 50 mg/kg/day IV over 2 hours x 1 day, total dose 50 mg/kg will be administered on Day -6.
Fludarabine
40 mg/m\^2/day intravenously on Days -6, -5, -4, -3 and -2.
Anti-thymocyte globulin
30 mg/kg on Days -4, -3 and -2.
Mesenchymal stem cell transplantation
infused via intravenous drip on Day 0
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.
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.
JEB MAC
Junctional EB (JEB) - Myeloablative conditioning (MAC) Participants receive Myeloablative Busulfan (targeting AUC 1000 umol/min), Fludarabine 75 mg/m2, and Cyclophosphamide 200 mg/kg
Cyclophosphamide
Cyclophosphamide 50 mg/kg/day IV over 2 hours x 1 day, total dose 50 mg/kg will be administered on Day -6.
Fludarabine
40 mg/m\^2/day intravenously on Days -6, -5, -4, -3 and -2.
Myeloablative Busulfan
Targeting AUC 1000 umol/min
Mesenchymal stem cell transplantation
infused via intravenous drip on Day 0
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.
JEB RIC
Junctional EB (JEB) - Reduced Intensity Condition Participants received Fludarabine 500 mg/m2, Cyclosphosphamide 50 mg/kg, equine Anti-thymocyte globulin 90 mg/kg, and low dose total body irradiation (either 200 or 300 cGy)
Cyclophosphamide
Cyclophosphamide 50 mg/kg/day IV over 2 hours x 1 day, total dose 50 mg/kg will be administered on Day -6.
Fludarabine
40 mg/m\^2/day intravenously on Days -6, -5, -4, -3 and -2.
Anti-thymocyte globulin
30 mg/kg on Days -4, -3 and -2.
Mesenchymal stem cell transplantation
infused via intravenous drip on Day 0
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.
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.
Interventions
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Cyclophosphamide
Cyclophosphamide 50 mg/kg/day IV over 2 hours x 1 day, total dose 50 mg/kg will be administered on Day -6.
Fludarabine
40 mg/m\^2/day intravenously on Days -6, -5, -4, -3 and -2.
Anti-thymocyte globulin
30 mg/kg on Days -4, -3 and -2.
Myeloablative Busulfan
Targeting AUC 1000 umol/min
Mesenchymal stem cell transplantation
infused via intravenous drip on Day 0
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.
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 Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
Exclusion Criteria
* 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.
25 Years
ALL
No
Sponsors
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Masonic Cancer Center, University of Minnesota
OTHER
Responsible Party
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Principal Investigators
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Jakub Tolar, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Masonic Cancer Center, University of Minnesota
Locations
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University of Minnesota Masonic Cancer Center and Medical Center
Minneapolis, Minnesota, United States
Countries
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Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Document Type: Informed Consent Form
Other Identifiers
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0911M74035
Identifier Type: OTHER
Identifier Source: secondary_id
MT2009-09
Identifier Type: -
Identifier Source: org_study_id
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