NCT01033552

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

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 32 (actual)
• Sponsor: Masonic Cancer Center, University of Minnesota · Academic / Other
• Sex: All
• Age: 25 Years
• Healthy volunteers: Not accepted

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.

Detailed description

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.

Conditions

• Epidermolysis Bullosa

Interventions

Type	Name	Description
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.
DRUG	Fludarabine	40 mg/m\^2/day intravenously on Days -6, -5, -4, -3 and -2.
DRUG	Anti-thymocyte globulin	30 mg/kg on Days -4, -3 and -2.
DRUG	Myeloablative Busulfan	Targeting AUC 1000 umol/min
PROCEDURE	Mesenchymal stem cell transplantation	infused via intravenous drip on Day 0
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.

Timeline

• Start date: 2010-01-01
• Primary completion: 2021-08-12
• Completion: 2021-08-12
• First posted: 2009-12-16
• Last updated: 2024-04-03
• Results posted: 2024-04-03

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study