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

NCT00881556 | Terminated Early Phase 1 DMC FDA Drug

• 2 other identifiers: AAAD5420CHNY-08-536
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 3

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.

Conditions

Epidermolysis Bullosa

Keywords

Allogeneic Stem Cell Transplant; AlloSCT; RDEB; recessive dystrophic epidermolysis bullosa

Outcome Measures

Primary Outcomes (2)

• Event-free survival (EFS)

  Up to 2 years

• Overall Survival (OS)

  Up to 2 years

Secondary Outcomes (2)

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

  Up to Day +730

• Percentage of donor skin dermal chimerism following RIC and AlloSCT in selected patients with RDEB.

  Up to Day +730

Study Arms (1)

RIC Group

EXPERIMENTAL

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; Drug: Fludarabine; Drug: Busulfan; Drug: Lorazepam; Drug: Alemtuzumab; Drug: Tacrolimus

Interventions

Palifermin DRUG

60 mcg/kg/day for 6 days

Also known as: Kepivance

RIC Group

Fludarabine DRUG

30 mg/m2 IV x 1 for 6 days

Also known as: Fludara

RIC Group

Busulfan DRUG

4 mg/kg/day IV divided BID for 4 days

Also known as: Myleran

RIC Group

Lorazepam DRUG

0.02-0.05 mg/kg for 5 days

Also known as: Ativan

RIC Group

Alemtuzumab DRUG

20 mg/m2 IV for 5 days

Also known as: Lemtrada

RIC Group

Tacrolimus DRUG

0.03mg/kg/24 hours as continuous infusion for 4 days

Also known as: Prograf, Protopic, Hecoria

RIC Group

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• Karnofsky/Lansky Performance Score \<50%
• Pregnant or nursing
• Uncontrolled bacterial, viral or mold infection
• History or presence of skin squamous cell carcinoma

Sponsors & Collaborators

• Columbia University: lead

Study Sites (3)

The Children's Hospital

Aurora, Colorado, 80045, United States

Location

Children's Memorial Hospital

Chicago, Illinois, 60614, United States

Location

Morgan Stanley Children's Hospital of NYP

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Epidermolysis Bullosa; Epidermolysis Bullosa Dystrophica

Interventions

Fibroblast Growth Factor 7; fludarabine; fludarabine phosphate; Busulfan; Lorazepam; Alemtuzumab; Tacrolimus

Condition Hierarchy (Ancestors)

Skin Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Vesiculobullous; Collagen Diseases; Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Fibroblast Growth Factors; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Benzodiazepinones; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Macrolides; Lactones

Study Officials

• Angela Christiano, PhD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2009
• First Posted: April 15, 2009
• Study Start: August 20, 2009
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: August 17, 2021

Record last verified: 2021-08

Locations

US (3)