Clinical Trial: Allogeneic Stem Cell Transplantation (ALLOSCT) in Recessive Dystrophic Epidermolysis Bullosa (RDEB)

Study Status: Recruiting
Recruit Status: Unknown status
Study Type: Interventional

Official Title: A Pilot Study of Reduced Intensity Conditioning (RIC) and Allogeneic Stem Cell Transplantation (ALLOSCT) In Children With Recessive Dystrophic Epidermolysis Bullosa (RDEB)

Brief Summary:

Reduced Intensity Conditioning (RIC) and Allogeneic Stem Cell Transplantation (AlloSCT) from family-related donors and unrelated cord blood (UCB) donors will be safe and well tolerated in selected patients with RDEB.

To determine the event-free survival (EFS) and overall survival (OS) following RIC consisting of busulfan/fludarabine/alemtuzumab (BFA) and AlloSCT in selected patients with RDEB.


Detailed Summary:

Epidermolysis bullosa (EB), is a diverse group of genodermatoses, which is considered a rare and orphan disease and affects approximately 1 in 20,000 people in the United States for a cumulative total of close to 20,000[1-4]. There are three major subtypes of inherited EB, including EB simplex (EBS), junctional EB (JEB), and dystrophic EB[1-4]. RDEB is among the most severe and represents approximately 10% of all forms of EB[1-4]. A rough estimate would then project that there are several thousand patients with RDEB in the U.S. at the current time. Up to 30 different clinical phenotypes and mutations in at least 10 structural genes in different sub-types of EB have been reported[4-8]. In addition to heritable subtypes of EB, there is an acquired autoimmune form in which the patients develop auto-antibodies directed against similar proteins of the inherited dystrophic forms of EB, including EB acquisita (EBA).

We have previously reported our experience with RIC with BFA [48] in pediatric AlloSCT recipients (mean age 9.5 yrs [1.4-21], 11/4 M/F, 10 non-malignant, 5 malignant disease, [6 sibling, 5 UCB, 5 matched unrelated donor]); median time to ANC ≥ 500/mm3 and platelet count ≥20K/mm3 was 22 and 30 days, respectively. Probability of day +180 and 365 donor chimerism was 90% (Figure 7), and OS was 95% (Figure 8). This conditioning regimen therefore results in a high degree of donor chimerism and survival with minimal regimen related mortality.


Sponsor: Columbia University

Current Primary Outcome: To determine the event-free survival (EFS) and overall survival (OS) following RIC consisting of busulfan/fludarabine/alemtuzumab (BFA) and AlloSCT in selected patients with RDEB. [ Time Frame: Day+30, Day+60, Day+100, 1year, 2 years ]

Original Primary Outcome: To determine the event-free survival (EFS) and overall survival (OS) following RIC consisting of busulfan/fludarabine/alemtuzumab (BFA) and AlloSCT in selected patients with RDEB. [ Time Frame: 5 years ]

Current Secondary Outcome:

  • Quantitate the percent of whole blood (CD45), T-cell (CD3), and NK cell (CD56) chimerism following RIC and AlloSCT in selected patients with RDEB [ Time Frame: Pre transplant, Day +60, Day +100, Day +180, Day +365, Day +730 ]
  • Quantitate the percent of donor skin dermal chimerism following RIC and AlloSCT in selected patients with RDEB. [ Time Frame: Pre Transplant, Day +30, Day +60, Day +100, Day +180, Day +365, Day +730 ]
  • Compare the gene and protein expression of COL7A1 in the skin pre and post AlloSCT [ Time Frame: Pre- Transplant, Day +30, Day +60, Day +100, Day +180, Day +365, Day +730 ]


Original Secondary Outcome:

  • Quantitate the percent of whole blood (CD45), T-cell (CD3), and NK cell (CD56) chimerism following RIC and AlloSCT in selected patients with RDEB [ Time Frame: 5 years ]
  • Quantitate the percent of donor skin dermal chimerism following RIC and AlloSCT in selected patients with RDEB. [ Time Frame: 5 years ]
  • Compare the gene and protein expression of COL7A1 in the skin pre and post AlloSCT [ Time Frame: 5 years ]


Information By: Columbia University

Dates:
Date Received: April 14, 2009
Date Started: March 2009
Date Completion: July 2014
Last Updated: February 14, 2012
Last Verified: February 2012