Epidermolysis BullosaNCT00478244
Allogeneic Hematopoietic Stem Cell Transplant For Epidermolysis Bullosa
A study testing busulfan, cyclophosphamide and fludarabine phosphate in people with Epidermolysis Bullosa, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial summary
RATIONALE: In animal models, stem cells have been shown to home to the skin and repair the biochemical and structural abnormalities associated with recessive dystrophic epidermolysis bullosa (RDEB) (collagen 7 deficiency). Read more about this study
- Who is it for?
- Ages Up to 25 years
- Conditions the study is for
- Epidermolysis Bullosa
- What is being tested?
- busulfan, cyclophosphamide and fludarabine phosphate
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2007to Aug 2011
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnosis of epidermolysis bullosa (EB)
- Documented collagen type VII deficiency by:
- Antigenic mapping (LH7.2 antibody)
- Ultrastructure analysis of anchoring fibrils
- DNA mutation analysis
- Performance status: >50% Lansky; >50% Karnofsky
Show all 15Show fewer
- Adequate organ function
- Renal: glomerular filtration rate > 60ml/min/1.73m2 patients aged ≤ 10 years
- Hepatic: bilirubin, aspartate aminotransferase/alanine aminotransferase (AST/ALT), Alkaline phosphatase (ALP) < 5 x upper limit of normal 4.2.3 Pulmonary: oxygen saturation >92% 4.2.4 Cardiac: left ventricular ejection fraction > 45%.
- Healthy related hematopoietic stem cell donor available and meeting 1 of the following criteria:
- HLA-A, B, DRB1-identical sibling bone marrow and/or umbilical cord blood donor (first priority)
- HLA-A, B, DRB1-matched or partially matched related donor (second priority)
- Donor may be a carrier but must be unaffected by EB
- 8/8 HLA A, B, C, DRB1 allele level matched unrelated marrow donor (third priority)
- 7/8 HLA-A, B, C, DRB1 allele level matched unrelated marrow donor or 4/6 HLA-A, B (antigen level), DRB1 (allele level) matched unrelated cord blood donor (fourth priority)
Who cannot join
- Active infection at time of transplantation (including active infection with Aspergillus or other mold within 30 days)
- Squamous cell carcinoma of the skin
- History of human immunodeficiency virus (HIV) infection
- Prior transplantation with donor skin
Trial locations and contacts
1 site in 1 country.
United States1 site
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, 55455
About this study
Official title: Allogeneic Hematopoietic Cell Transplantation to Correct the Biochemical Defect and Create Tolerance to Donor Tissue in Subjects With Epidermolysis Bullosa
RATIONALE: In animal models, stem cells have been shown to home to the skin and repair the biochemical and structural abnormalities associated with recessive dystrophic epidermolysis bullosa (RDEB) (collagen 7 deficiency).
PURPOSE: To determine the safety and effectiveness of stem cell infusion in the treatment of RDEB.
Read the detailed description
OBJECTIVES:
Primary
- Estimate the incidence of detectable donor-derived collagen type VII at day 100 in patients with epidermolysis bullosa by donor.
Secondary
- Determine the incidence of transplant-related mortality at day 180
- Determine the incidence of blood chimerism at days 21, 100, 180, 365, and 730
- Determine the incidence of neutrophil recovery at day 42 and platelet recovery at day 180
- Determine the incidence of acute graft-versus-host disease (GVHD) grade II-IV and grade III-IV at day 100
- Determine the incidence of chronic GVHD at 1 year
- Determine the probability of survival at 1 and 2 years
- Determine the incidence of donor derived cells in the skin
- Determine resistance to blister formation OUTLINE: This is an open-label, pilot study.
- Conditioning regimen: Busulfan intravenously (IV) over 2 hours every 6 hours on days -9 to -4, fludarabine phosphate IV over 1 hour on days -5 to -3, and high-dose cyclophosphamide IV over 1 hour on days -5 to -2.
- Stem cell transplantation on day 0.
After completion of study treatment, patients are followed periodically for at least 5 years.
PROJECTED ACCRUAL: 30 patients
- Conditions
- Epidermolysis Bullosa
- Being tested
- busulfan, cyclophosphamide, fludarabine phosphate, hematopoietic bone marrow transplantation
- Keywords
- epidermolysis bullosa, 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.
busulfanDrug
Also called Bulsulfex
Day -9 through Day -6: 1.1 mg/kg if < 12 kg IV every 6 hours; 0.8 mg/kg if > 12 kg.
cyclophosphamideDrug
Also called Cytoxan
Day -5 through Day -2: 50 mg/kg IV over 120 min.
Also called Fludarabine, Fludara
Day -5 through Day -3: 25 mg/m2 IV over 60 min.
hematopoietic bone marrow transplantationProcedure or surgery
Also called Bone marrow transplant
allogeneic bone marrow, peripheral stem cell or umbilical cord blood transplantation
| Study group | Role | What they receive |
|---|---|---|
| Epidermolysis Bullosa (EB) Patients | Experimental | Epidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant. Receives: Drug: busulfan; Drug: cyclophosphamide; Drug: fludarabine phosphate; Procedure: hematopoietic bone marrow transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With Detectable Collagen Type VII
Number of patients with epidermolysis bullosa who had collagen type VII. Type VII collagen defects cause recessive dystrophic epidermolysis bullosa (RDEB), a blistering skin disorder often accompanied by epidermal cancers.
Measured: Day 100 Post Transplant
Secondary outcomes (9)
Number of Patients With >70% Donor Chimerism
Number of patients with donor chimerism - percentage of donor cells in the patient via the peripheral blood or bone marrow.
Measured: Days 21, 100, 180, 365 and 730 Post Transplant
Number of Patients With Transplant-Related Mortality
Number of patients who died due to complications of the transplant (includes all deaths without previous relapse or progression).
Measured: Day 180 Post Transplant
Number of Patients With Platelet Engraftment
Number of patients with a platelet count >5 x 10^10 cells/liter for 3 consecutive measurements.
Measured: Day 180 Post Transplant
Number of Patients With Acute Graft-Versus-Host Disease (GVHD)
Number of patients with GVHD. Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.
Measured: Day 100 Post Transplant
Number of Patients With Chronic Graft-Versus-Host Disease (cGVHD)
Number of patients with cGVHD; a severe long-term complication created by infusion of donor cells into a foreign host.
Measured: Day 365 Post Transplant
Overall Survival
Survival is defined as the number of patients that were alive post transplant.
Measured: 1 year and 2 years Post Transplant
Number of Patients With Donor Derived Cells in Skin
Number of patients who had donor skin chimerism - donor cells in the patient's epidermis (a state in bone marrow transplantation in which bone marrow and host cells exist compatibly without signs of graft-versus-host rejection disease).
Measured: Day 90 Post Transplant
Number of Patients With Resistance to Blister Formation
Resistance to Blister Formation demonstrated by response to negative pressure.
Measured: Month 1 through Month 24 Inclusive
Number of Patients With Neutrophil Engraftment
Number of patients with an absolute neutrophil count >5 x 10^8 cells/liter for 3 consecutive days.
Measured: Day 42 Post Transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2007 (estimated)
- Study startApr 2007
- Primary completionAug 2011
- Study completionAug 2011
Why it stopped: Competing studies
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Epidermolysis BullosaStudies of the same condition, open and under way.
- More trials run by Masonic Cancer Center, University of MinnesotaThe 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
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- John E. Wagner, MD, Study chair, Masonic Cancer Center, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00478244
- Sponsor's protocol ID
- MT2006-15
- Other IDs
- CDR0000546620, UMN-0702M01504
- Status last verified
- Dec 2017
- First submitted
- 23 May 2007
- Last updated
- 28 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Wagner JE, Ishida-Yamamoto A, McGrath JA, Hordinsky M, Keene DR, Woodley DT, Chen M, Riddle MJ, Osborn MJ, Lund T, Dolan M, Blazar BR, Tolar J. Bone marrow transplantation for recessive dystrophic epidermolysis bullosa. N Engl J Med. 2010 Aug 12;363(7):629-39. doi: 10.1056/NEJMoa0910501.
PubMed 20818854
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Allogeneic Hematopoietic Cell Transplantation to Correct the Biochemical Defect and Create Tolerance to Donor Tissue in Subjects With Epidermolysis Bullosa
- ClinicalTrials.gov ID
- NCT00478244
- Acronym / sponsor ID
- MT2006-15
- Conditions
- Epidermolysis Bullosa
- Keywords
- epidermolysis bullosa, dystrophic epidermolysis bullosa
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Competing studies
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Study start
- Apr 2007
- Primary completion
- Aug 2011 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 24 May 2007 (estimated)
- Results
- Posted 11 Feb 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: In animal models, stem cells have been shown to home to the skin and repair the biochemical and structural abnormalities associated with recessive dystrophic epidermolysis bullosa (RDEB) (collagen 7 deficiency).
PURPOSE: To determine the safety and effectiveness of stem cell infusion in the treatment of RDEB.
Detailed description
OBJECTIVES:
Primary
- Estimate the incidence of detectable donor-derived collagen type VII at day 100 in patients with epidermolysis bullosa by donor.
Secondary
- Determine the incidence of transplant-related mortality at day 180
- Determine the incidence of blood chimerism at days 21, 100, 180, 365, and 730
- Determine the incidence of neutrophil recovery at day 42 and platelet recovery at day 180
- Determine the incidence of acute graft-versus-host disease (GVHD) grade II-IV and grade III-IV at day 100
- Determine the incidence of chronic GVHD at 1 year
- Determine the probability of survival at 1 and 2 years
- Determine the incidence of donor derived cells in the skin
- Determine resistance to blister formation OUTLINE: This is an open-label, pilot study.
- Conditioning regimen: Busulfan intravenously (IV) over 2 hours every 6 hours on days -9 to -4, fludarabine phosphate IV over 1 hour on days -5 to -3, and high-dose cyclophosphamide IV over 1 hour on days -5 to -2.
- Stem cell transplantation on day 0.
After completion of study treatment, patients are followed periodically for at least 5 years.
PROJECTED ACCRUAL: 30 patients
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Epidermolysis Bullosa (EB) Patients | Experimental | Drug: busulfan, Drug: cyclophosphamide, Drug: fludarabine phosphate, Procedure: hematopoietic bone marrow transplantationEpidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant. |
Who may qualify
- Ages
- Up to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (15 listed)
- Diagnosis of epidermolysis bullosa (EB)
- Performance status: >50% Lansky; >50% Karnofsky
- Adequate organ function
- Healthy related hematopoietic stem cell donor available and meeting 1 of the following criteria:
Key exclusion criteria (4 listed)
- Active infection at time of transplantation (including active infection with Aspergillus or other mold within 30 days)
- Squamous cell carcinoma of the skin
- History of human immunodeficiency virus (HIV) infection
- Prior transplantation with donor skin
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 |
|---|---|---|
| busulfanAlso: BulsulfexDay -9 through Day -6: 1.1 mg/kg if < 12 kg IV every 6 hours; 0.8 mg/kg if > 12 kg. | Drug | Epidermolysis Bullosa (EB) Patients |
| cyclophosphamideAlso: CytoxanDay -5 through Day -2: 50 mg/kg IV over 120 min. | Drug | Epidermolysis Bullosa (EB) Patients |
| fludarabine phosphateAlso: Fludarabine, FludaraDay -5 through Day -3: 25 mg/m2 IV over 60 min. | Drug | Epidermolysis Bullosa (EB) Patients |
| hematopoietic bone marrow transplantationAlso: Bone marrow transplantallogeneic bone marrow, peripheral stem cell or umbilical cord blood transplantation | Procedure or surgery | Epidermolysis Bullosa (EB) Patients |
Primary outcome
Number of Patients With Detectable Collagen Type VII
Time frame: Day 100 Post Transplant
Number of patients with epidermolysis bullosa who had collagen type VII. Type VII collagen defects cause recessive dystrophic epidermolysis bullosa (RDEB), a blistering skin disorder often accompanied by epidermal cancers.
9 secondary outcomes
Number of Patients With >70% Donor Chimerism
Time frame: Days 21, 100, 180, 365 and 730 Post Transplant
Number of Patients With Transplant-Related Mortality
Time frame: Day 180 Post Transplant
Number of Patients With Platelet Engraftment
Time frame: Day 180 Post Transplant
Number of Patients With Acute Graft-Versus-Host Disease (GVHD)
Time frame: Day 100 Post Transplant
Number of Patients With Chronic Graft-Versus-Host Disease (cGVHD)
Time frame: Day 365 Post Transplant
Overall Survival
Time frame: 1 year and 2 years Post Transplant
Number of Patients With Donor Derived Cells in Skin
Time frame: Day 90 Post Transplant
Number of Patients With Resistance to Blister Formation
Time frame: Month 1 through Month 24 Inclusive
Number of Patients With Neutrophil Engraftment
Time frame: Day 42 Post Transplant
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 20818854Wagner JE, Ishida-Yamamoto A, McGrath JA, Hordinsky M, Keene DR, Woodley DT, Chen M, Riddle MJ, Osborn MJ, Lund T, Dolan M, Blazar BR, Tolar J. Bone marrow transplantation for recessive dystrophic epidermolysis bullosa. N Engl J Med. 2010 Aug 12;363(7):629-39. doi: 10.1056/NEJMoa0910501.
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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.
John E. Wagner, MD study chair
Masonic Cancer Center, University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing busulfan, cyclophosphamide and fludarabine phosphate in people with Epidermolysis Bullosa, run by Masonic Cancer Center, University of Minnesota at 1 site 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 15 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 28 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Feb 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Patients With Detectable Collagen Type VII (time frame: Day 100 Post Transplant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00478244, which also lists 1 linked publication.
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 28 Dec 2017.