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

Primary Purpose

Epidermolysis Bullosa

Status
Terminated
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Palifermin
Fludarabine
Busulfan
Lorazepam
Alemtuzumab
Tacrolimus
Sponsored by
Columbia University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Epidermolysis Bullosa focused on measuring Allogeneic Stem Cell Transplant, AlloSCT, RDEB, recessive dystrophic epidermolysis bullosa

Eligibility Criteria

undefined - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • The Children's Hospital
  • Children's Memorial Hospital
  • Morgan Stanley Children's Hospital of NYP

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

RIC Group

Arm 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

Outcomes

Primary Outcome Measures

Event-free survival (EFS)
Overall Survival (OS)

Secondary Outcome Measures

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

Full Information

First Posted
April 14, 2009
Last Updated
August 13, 2021
Sponsor
Columbia University
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1. Study Identification

Unique Protocol Identification Number
NCT00881556
Brief Title
Allogeneic Stem Cell Transplantation (ALLOSCT) in Recessive Dystrophic Epidermolysis Bullosa (RDEB)
Acronym
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)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2021
Overall Recruitment Status
Terminated
Study Start Date
August 20, 2009 (Actual)
Primary Completion Date
September 2015 (Actual)
Study Completion Date
September 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Columbia University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epidermolysis Bullosa
Keywords
Allogeneic Stem Cell Transplant, AlloSCT, RDEB, recessive dystrophic epidermolysis bullosa

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
RIC Group
Arm Type
Experimental
Arm 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
Intervention Type
Drug
Intervention Name(s)
Palifermin
Other Intervention Name(s)
Kepivance
Intervention Description
60 mcg/kg/day for 6 days
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fludara
Intervention Description
30 mg/m2 IV x 1 for 6 days
Intervention Type
Drug
Intervention Name(s)
Busulfan
Other Intervention Name(s)
Myleran
Intervention Description
4 mg/kg/day IV divided BID for 4 days
Intervention Type
Drug
Intervention Name(s)
Lorazepam
Other Intervention Name(s)
Ativan
Intervention Description
0.02-0.05 mg/kg for 5 days
Intervention Type
Drug
Intervention Name(s)
Alemtuzumab
Other Intervention Name(s)
Lemtrada
Intervention Description
20 mg/m2 IV for 5 days
Intervention Type
Drug
Intervention Name(s)
Tacrolimus
Other Intervention Name(s)
Prograf, Protopic, Hecoria
Intervention Description
0.03mg/kg/24 hours as continuous infusion for 4 days
Primary Outcome Measure Information:
Title
Event-free survival (EFS)
Time Frame
Up to 2 years
Title
Overall Survival (OS)
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
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
Title
Percentage of donor skin dermal chimerism following RIC and AlloSCT in selected patients with RDEB.
Time Frame
Up to Day +730

10. Eligibility

Sex
All
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
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: 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 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 Adequate cardiac function defined as: Shortening fraction of ≥28% by echocardiogram, or Ejection fraction of ≥48% by radionuclide angiogram or echocardiogram 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Angela Christiano, PhD
Organizational Affiliation
Columbia University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Children's Hospital
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Children's Memorial Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60614
Country
United States
Facility Name
Morgan Stanley Children's Hospital of NYP
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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

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