Stem Cell Transplant for Epidermolysis Bullosa
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.
Drug: Anti-thymocyte globulin
Drug: Cyclosporine A
Drug: Mycophenolate mofetil
Procedure: Mesenchymal stem cell transplantation
Radiation: Total body irradiation
Procedure: Umbilical cord blood stem cell transplantation
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Biochemical Correction of Severe Epidermolysis Bullosa by Allogeneic Stem Cell Transplantation|
- Event-free survival [ Time Frame: 1 year and 2 Years Post-transplant ] [ Designated as safety issue: No ]
- Incidence of transplant-related mortality (TRM) [ Time Frame: 180 Days Post Transplant ] [ Designated as safety issue: Yes ]
- Pattern of biochemical improvement measured by increase in protein expression (collagen, laminin, integrin or plakin) [ Time Frame: Through 1 Year Post-Transplant ] [ Designated as safety issue: No ]
- Quality of Life [ Time Frame: Pretreatment, Day 365 and Day 730 ] [ Designated as safety issue: No ]
|Study Start Date:||January 2010|
|Estimated Study Completion Date:||October 2019|
|Estimated Primary Completion Date:||October 2019 (Final data collection date for primary outcome measure)|
Experimental: transplant in Epidermolysis Bullosa
Patients with severe Epidermolysis Bullosa undergoing mesenchymal stem cell transplantation or umbilical cord blood stem cell transplantation will receive pre-transplant conditioning regimens consisting of cyclophosphamide, fludarabine monophosphate, anti-thymocyte globulin and total body irradiation, and post-transplant immunosuppressive therapy using Cyclosporine A and Mycophenolate Mofetil (MMF).
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: CytoxanDrug: Fludarabine
40 mg/m^2/day intravenously on Days -5, -4, -3 and -2.
Other Name: FludaraDrug: Anti-thymocyte globulin
30 mg/kg on Days -4, -3 and -2.
Other Name: ATGDrug: 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: CSADrug: 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: MSCTRadiation: 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: Umbilical cord blood stem cell transplantation
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
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, structual 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01033552
|Contact: Patricia Kleinke, RNemail@example.com|
|United States, Minnesota|
|University of Minnesota Masonic Cancer Center and Medical Center||Recruiting|
|Minneapolis, Minnesota, United States, 55455|
|Contact: Patricia Kleinke, RN 612-273-0857 firstname.lastname@example.org|
|Principal Investigator: John E Wagner, MD|
|Principal Investigator:||John E. Wagner, MD||Masonic Cancer Center, University of Minnesota|