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

Brief Title

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

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 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.
    

Study Phase

Early Phase 1

Study Type

Interventional

Primary Outcome

Event-free survival (EFS)

Secondary Outcome

 Percentage of whole blood (CD45), T-cell (CD3), and NK cell (CD56) chimerism following RIC and AlloSCT in selected patients with RDEB

Condition

Epidermolysis Bullosa

Intervention

Palifermin

Study Arms / Comparison Groups

 RIC Group

Description:  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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

3

Start Date

August 20, 2009

Completion Date

September 2015

Primary Completion Date

September 2015

Eligibility Criteria

        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
      

Gender

All

Ages

N/A - 21 Years

Accepts Healthy Volunteers

No

Contacts

Angela Christiano, PhD, , 

Location Countries

United States

Location Countries

United States

NCT ID

NCT00881556

Organization ID

AAAD5420

Secondary IDs

CHNY-08-536

Responsible Party

Sponsor

Study Sponsor

Columbia University

Study Sponsor

Angela Christiano, PhD, Principal Investigator, Columbia University

Verification Date

August 2021