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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
Information provided by (Responsible Party):
Columbia University

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.

Condition or disease Intervention/treatment Phase
Epidermolysis Bullosa Drug: Palifermin Drug: Fludarabine Drug: Busulfan Drug: Lorazepam Drug: Alemtuzumab Drug: Tacrolimus Early Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study of Reduced Intensity Conditioning (RIC) and Allogeneic Stem Cell Transplantation (ALLOSCT) In Children With Recessive Dystrophic Epidermolysis Bullosa (RDEB)
Actual Study Start Date : August 20, 2009
Actual Primary Completion Date : September 2015
Actual Study Completion Date : September 2015

Arm Intervention/treatment
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

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

Primary Outcome Measures :
  1. Event-free survival (EFS) [ Time Frame: Up to 2 years ]
  2. Overall Survival (OS) [ Time Frame: Up to 2 years ]

Secondary Outcome Measures :
  1. 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 ]
  2. Percentage of donor skin dermal chimerism following RIC and AlloSCT in selected patients with RDEB. [ Time Frame: Up to Day +730 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00881556

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United States, Colorado
The Children's Hospital
Aurora, Colorado, United States, 80045
United States, Illinois
Children's Memorial Hospital
Chicago, Illinois, United States, 60614
United States, New York
Morgan Stanley Children's Hospital of NYP
New York, New York, United States, 10032
Sponsors and Collaborators
Columbia University
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Principal Investigator: Angela Christiano, PhD Columbia University
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Responsible Party: Columbia University
ClinicalTrials.gov Identifier: NCT00881556    
Other Study ID Numbers: AAAD5420
CHNY-08-536 ( Other Identifier: CUMC )
First Posted: April 15, 2009    Key Record Dates
Last Update Posted: August 17, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Columbia University:
Allogeneic Stem Cell Transplant
recessive dystrophic epidermolysis bullosa
Additional relevant MeSH terms:
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Epidermolysis Bullosa
Epidermolysis Bullosa Dystrophica
Skin Abnormalities
Congenital Abnormalities
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases
Skin Diseases, Vesiculobullous
Collagen Diseases
Connective Tissue Diseases
Antineoplastic Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Alkylating Agents
Antineoplastic Agents, Alkylating
Myeloablative Agonists
Antineoplastic Agents, Immunological
Autonomic Agents
Peripheral Nervous System Agents