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

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ClinicalTrials.gov Identifier: NCT00881556
Recruitment Status : Terminated
First Posted : April 15, 2009
Last Update Posted : August 17, 2021
Sponsor:
Information provided by (Responsible Party):
Columbia University

Tracking Information
First Submitted Date  ICMJE April 14, 2009
First Posted Date  ICMJE April 15, 2009
Last Update Posted Date August 17, 2021
Actual Study Start Date  ICMJE August 20, 2009
Actual Primary Completion Date September 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 13, 2021)
  • Event-free survival (EFS) [ Time Frame: Up to 2 years ]
  • Overall Survival (OS) [ Time Frame: Up to 2 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 14, 2009)
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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 13, 2021)
  • Percentage of whole blood (CD45), T-cell (CD3), and NK cell (CD56) chimerism following RIC and AlloSCT in selected patients with RDEB [ Time Frame: Up to Day +730 ]
  • Percentage of donor skin dermal chimerism following RIC and AlloSCT in selected patients with RDEB. [ Time Frame: Up to Day +730 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 14, 2009)
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Allogeneic Stem Cell Transplantation (ALLOSCT) in Recessive Dystrophic Epidermolysis Bullosa (RDEB)
Official Title  ICMJE 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 Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Epidermolysis Bullosa
Intervention  ICMJE
  • Drug: Palifermin
    60 mcg/kg/day for 6 days
    Other Name: Kepivance
  • Drug: Fludarabine
    30 mg/m2 IV x 1 for 6 days
    Other Name: Fludara
  • Drug: Busulfan
    4 mg/kg/day IV divided BID for 4 days
    Other Name: Myleran
  • Drug: Lorazepam
    0.02-0.05 mg/kg for 5 days
    Other Name: Ativan
  • Drug: Alemtuzumab
    20 mg/m2 IV for 5 days
    Other Name: Lemtrada
  • Drug: Tacrolimus
    0.03mg/kg/24 hours as continuous infusion for 4 days
    Other Names:
    • Prograf
    • Protopic
    • Hecoria
Study Arms  ICMJE Experimental: RIC Group

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

Interventions:
  • Drug: Palifermin
  • Drug: Fludarabine
  • Drug: Busulfan
  • Drug: Lorazepam
  • Drug: Alemtuzumab
  • Drug: Tacrolimus
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: August 13, 2021)
3
Original Estimated Enrollment  ICMJE
 (submitted: April 14, 2009)
20
Actual Study Completion Date  ICMJE September 2015
Actual Primary Completion Date September 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00881556
Other Study ID Numbers  ICMJE AAAD5420
CHNY-08-536 ( Other Identifier: CUMC )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Current Responsible Party Columbia University
Original Responsible Party Mitchell S. Cairo MD, Columbia University Medical Center
Current Study Sponsor  ICMJE Columbia University
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Angela Christiano, PhD Columbia University
PRS Account Columbia University
Verification Date August 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP