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

Epidermolysis Bullosa Clinical Trial

— RDEB  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00881556
• Other study ID #: AAAD5420
• Secondary ID: CHNY-08-536
• Status: Terminated
• Phase: Early Phase 1
• Start date: August 20, 2009
• Est. completion date: September 2015

Study information

• Verified date: August 2021
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: September 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 21 Years

Eligibility

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
• 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 glomerular filtration rate (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:

• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase (AST)) or serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase (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 diffusing capacity of the lungs for carbon monoxide (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

Related Conditions & MeSH terms

• Epidermolysis Bullosa
• Epidermolysis Bullosa Dystrophica

Intervention

Drug:
• Palifermin
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

Locations

Country	Name	City	State
United States	The Children's Hospital	Aurora	Colorado
United States	Children's Memorial Hospital	Chicago	Illinois
United States	Morgan Stanley Children's Hospital of NYP	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Columbia University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free survival (EFS)		Up to 2 years
Primary	Overall Survival (OS)		Up to 2 years
Secondary	Percentage of whole blood (CD45), T-cell (CD3), and NK cell (CD56) chimerism following RIC and AlloSCT in selected patients with RDEB		Up to Day +730
Secondary	Percentage of donor skin dermal chimerism following RIC and AlloSCT in selected patients with RDEB.		Up to Day +730