Overview

This trial is active, not recruiting.

Condition epidermolysis bullosa
Treatment reduced intensity transplant conditioning
Phase phase 0
Sponsor Columbia University
Start date March 2009
End date June 2014
Trial size 20 participants
Trial identifier NCT00881556, AAAD5420, CHNY-08-536

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Reduced Intensity
reduced intensity transplant conditioning RIC
Palifermin (Kepivance®) 60 mcg/kg/day for 6 days Fludarabine 30 mg/m2 IV x 1 for 6 days Busulfan 4 mg/kg/day IV divided BID for 4 days Lorazepam 0.02-0.05 mg/kg for 5 days Alemtuzumab 20 mg/m2 IV for 5 days Tacrolimus 0.03mg/kg/24 hours as continuous infusion for 4 days

Primary Outcomes

Measure
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

Secondary Outcomes

Measure
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

Eligibility Criteria

Male or female participants up to 21 years old.

Inclusion Criteria: - Recessive Dystrophic Epidermolysis Bullosa (RDEB) - Diagnosis of RDEB using molecular diagnosis and sequencing of mutations - Skin biopsy to determine status of type VII collagen by IF, EM and q-PCR - Age ≤21 years - Patient must have adequate organ function as below: 1. Adequate renal function defined as: - Serum creatinine less than or equal to 1.5 x normal, or - Creatinine clearance or radioisotope GFR =40 ml/min/m2 or > 60 ml/min/1.73 m2 or an equivalent GFR as determined by the institutional normal range 2. Adequate liver function defined as: - SGOT (AST) or SGPT (ALT) < 5.0 x normal 3. Adequate cardiac function defined as: - Shortening fraction of ≥28% by echocardiogram, or - Ejection fraction of ≥48% by radionuclide angiogram or echocardiogram 4. Adequate pulmonary function defined as: - Uncorrected DLCO≥35% by pulmonary function test - For children who are uncooperative, no evidence of dyspnea at rest Exclusion Criteria: - Karnofsky/Lansky Performance Score <50% - Pregnant or nursing - Uncontrolled bacterial, viral or mold infection - History or presence of skin squamous cell carcinoma

Additional Information

Official title A Pilot Study of Reduced Intensity Conditioning (RIC) and Allogeneic Stem Cell Transplantation (ALLOSCT) In Children With Recessive Dystrophic Epidermolysis Bullosa (RDEB)
Principal investigator Angela Christiano, PhD
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in February 2012.
Information provided to ClinicalTrials.gov by Columbia University.