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

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

Tracking Information

• First Submitted Date: April 14, 2009
• First Posted Date: April 15, 2009
• Last Update Posted Date: August 17, 2021
• Actual Study Start Date: August 20, 2009
• Actual Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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 ]

Current Secondary Outcome Measures (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 (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: 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 Type: Interventional
• Study Phase: Early Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Epidermolysis Bullosa

Intervention

• 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

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

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: August 13, 2021): 3
• Original Estimated Enrollment (submitted: April 14, 2009): 20
• Actual Study Completion Date: September 2015
• Actual Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: up to 21 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00881556
• Other Study ID Numbers: 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

• Plan to Share IPD: Undecided

• Current Responsible Party: Columbia University
• Original Responsible Party: Mitchell S. Cairo MD, Columbia University Medical Center
• Current Study Sponsor: Columbia University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Angela Christiano, PhD; Columbia University

• PRS Account: Columbia University
• Verification Date: August 2021