Epidermolysis BullosaEarly Phase 1RDEBNCT00881556
Allogeneic Stem Cell Transplantation (ALLOSCT) in Recessive Dystrophic Epidermolysis Bullosa (RDEB)
A Early Phase 1 study testing Palifermin, Fludarabine and Busulfan in people with Epidermolysis Bullosa, run by Columbia University at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Epidermolysis Bullosa
- What is being tested?
- Palifermin, Fludarabine and Busulfan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 3 sitesUnited States
- Study dates
- 20 Aug 2009to Sep 2015
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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:
Show all 16Show fewer
- 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
Who cannot join
- Karnofsky/Lansky Performance Score <50%
- Pregnant or nursing
- Uncontrolled bacterial, viral or mold infection
- History or presence of skin squamous cell carcinoma
Trial locations and contacts
3 sites in 1 country.
United States3 sites
The Children's Hospital
Aurora, Colorado, 80045
Children's Memorial Hospital
Chicago, Illinois, 60614
Morgan Stanley Children's Hospital of NYP
New York, New York, 10032
About this study
Official title: A Pilot Study of Reduced Intensity Conditioning (RIC) and Allogeneic Stem Cell Transplantation (ALLOSCT) In Children With Recessive Dystrophic Epidermolysis Bullosa (RDEB)
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.
Read the 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.
- Conditions
- Epidermolysis Bullosa
- Being tested
- Palifermin, Fludarabine, Busulfan, Lorazepam, Alemtuzumab
- Keywords
- Allogeneic Stem Cell Transplant, AlloSCT, RDEB, recessive dystrophic epidermolysis bullosa
- Medical subject headings
- Epidermolysis Bullosa, Epidermolysis Bullosa Dystrophica
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PaliferminDrug
Also called Kepivance
60 mcg/kg/day for 6 days
FludarabineDrug
Also called Fludara
30 mg/m2 IV x 1 for 6 days
BusulfanDrug
Also called Myleran
4 mg/kg/day IV divided BID for 4 days
LorazepamDrug
Also called Ativan
0.02-0.05 mg/kg for 5 days
AlemtuzumabDrug
Also called Lemtrada
20 mg/m2 IV for 5 days
TacrolimusDrug
Also called Prograf, Protopic, Hecoria
0.03mg/kg/24 hours as continuous infusion for 4 days
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Palifermin; Drug: Fludarabine; Drug: Busulfan; Drug: Lorazepam; Drug: Alemtuzumab; Drug: Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-free survival (EFS)
Measured: Up to 2 years
Overall Survival (OS)
Measured: 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
Measured: Up to Day +730
Percentage of donor skin dermal chimerism following RIC and AlloSCT in selected patients with RDEB.
Measured: Up to Day +730
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2009 (estimated)
- Study start20 Aug 2009
- Primary completionSep 2015
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Epidermolysis BullosaStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Angela Christiano, PhD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00881556
- Sponsor's protocol ID
- AAAD5420
- Other IDs
- CHNY-08-536
- Acronym
- RDEB
- Status last verified
- Aug 2021
- First submitted
- 14 Apr 2009
- Last updated
- 17 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Reduced Intensity Conditioning (RIC) and Allogeneic Stem Cell Transplantation (ALLOSCT) In Children With Recessive Dystrophic Epidermolysis Bullosa (RDEB)
- ClinicalTrials.gov ID
- NCT00881556
- Acronym / sponsor ID
- RDEB / AAAD5420
- Conditions
- Epidermolysis Bullosa
- Keywords
- Allogeneic Stem Cell Transplant, AlloSCT, RDEB, recessive dystrophic epidermolysis bullosa
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Study start
- 20 Aug 2009 (actual)
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 15 Apr 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RIC Group | Experimental | Drug: Palifermin, Drug: Fludarabine, Drug: Busulfan, Drug: Lorazepam, Drug: Alemtuzumab, Drug: TacrolimusReduced 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 |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (16 listed)
- 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:
Key exclusion criteria (4 listed)
- Karnofsky/Lansky Performance Score <50%
- Pregnant or nursing
- Uncontrolled bacterial, viral or mold infection
- History or presence of skin squamous cell carcinoma
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PaliferminAlso: Kepivance60 mcg/kg/day for 6 days | Drug | RIC Group |
| FludarabineAlso: Fludara30 mg/m2 IV x 1 for 6 days | Drug | RIC Group |
| BusulfanAlso: Myleran4 mg/kg/day IV divided BID for 4 days | Drug | RIC Group |
| LorazepamAlso: Ativan0.02-0.05 mg/kg for 5 days | Drug | RIC Group |
| AlemtuzumabAlso: Lemtrada20 mg/m2 IV for 5 days | Drug | RIC Group |
| TacrolimusAlso: Prograf, Protopic, Hecoria0.03mg/kg/24 hours as continuous infusion for 4 days | Drug | RIC Group |
Primary outcome
Event-free survival (EFS)
Time frame: Up to 2 years
Overall Survival (OS)
Time frame: Up to 2 years
2 secondary outcomes
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
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2021.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Angela Christiano, PhD principal investigator
Columbia University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Palifermin, Fludarabine and Busulfan in people with Epidermolysis Bullosa, run by Columbia University at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event-free survival (EFS) (time frame: Up to 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2021.