Biochemical Correction of Severe EB by Allo HSCT and "Off-the-shelf" MSCs
MT2009-09: Biochemical Correction of Severe Epidermolysis Bullosa by Allogeneic Stem Cell Transplantation and "Off-the-shelf" Mesenchymal Stem Cells
2 other identifiers
interventional
32
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jan 2010
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 14, 2009
CompletedFirst Posted
Study publicly available on registry
December 16, 2009
CompletedStudy Start
First participant enrolled
January 1, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 12, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
August 12, 2021
CompletedResults Posted
Study results publicly available
April 3, 2024
CompletedApril 3, 2024
March 1, 2024
11.6 years
December 14, 2009
December 5, 2023
March 6, 2024
Conditions
Outcome Measures
Primary Outcomes (1)
Percentage of Participants With Event-free Survival
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. Assessed at follow up appointments through questionnaire and patient samples.
1 year and 2 Years Post-transplant
Secondary Outcomes (6)
Percentage of Participants Transplant-related Mortality (TRM)
180 Days Post Transplant
Average Biochemical Improvement
1 Year Post-Transplant
Measure Patients Quality of Life Using a Questionnaire
Pretreatment and 1 year
Durability of HSC Donor Engraftment in the Skin
100 Days
Probability of Survival
1 Year
- +1 more secondary outcomes
Study Arms (4)
RDEB Mac
EXPERIMENTALRecessive Dystrophic EB (RDEB) - Myeloablative conditioning (MAC) Participants receive Myeloablative Busulfan (targeting AUC 1000 umol/min), Fludarabine 75 mg/m2, and Cyclophosphamide 200 mg/kg
RDEB RIC
EXPERIMENTALRecessive 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)
JEB MAC
EXPERIMENTALJunctional EB (JEB) - Myeloablative conditioning (MAC) Participants receive Myeloablative Busulfan (targeting AUC 1000 umol/min), Fludarabine 75 mg/m2, and Cyclophosphamide 200 mg/kg
JEB RIC
EXPERIMENTALJunctional 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)
Interventions
Cyclophosphamide 50 mg/kg/day IV over 2 hours x 1 day, total dose 50 mg/kg will be administered on Day -6.
40 mg/m\^2/day intravenously on Days -6, -5, -4, -3 and -2.
infused via intravenous drip on Day 0
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 UCB products will be infused as soon as the product arrives and within 30 minutes. The product is infused via IV drip.
Eligibility Criteria
You may qualify if:
- 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
- /8 HLA matched donor at HLA-A, B, C, DRB1
- Unrelated Donor
- Marrow
- HLA-A, B, C, DRB1 phenotypic identical donor
- +6 more criteria
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of Minnesota Masonic Cancer Center and Medical Center
Minneapolis, Minnesota, 55455, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Jakub Tolar
- Organization
- University of Minnesota, Masonic Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Jakub Tolar, MD, PhD
Masonic Cancer Center, University of Minnesota
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 14, 2009
First Posted
December 16, 2009
Study Start
January 1, 2010
Primary Completion
August 12, 2021
Study Completion
August 12, 2021
Last Updated
April 3, 2024
Results First Posted
April 3, 2024
Record last verified: 2024-03