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Epidermolysis BullosaPhase 1/2NCT01033552

Biochemical Correction of Severe EB by Allo HSCT and "Off-the-shelf" MSCs

A Phase 1/2 study testing Cyclophosphamide, Fludarabine and Anti-thymocyte globulin in people with Epidermolysis Bullosa, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is an open-label, single institution, phase II study in patients with epidermolysis bullosa (EB). The underlying hypothesis is that the infusion of bone marrow or umbilical cord blood from a healthy unaffected donor will correct the collagen, laminin, integrin, or plakin deficiency and reduce the skin fragility… 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?
Cyclophosphamide, Fludarabine and Anti-thymocyte globulin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
1 siteUnited States
Study dates
Jan 2010to 12 Aug 2021
Phase
Phase 1/2
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 severe form of epidermolysis bullosa (EB) characterized by collagen, laminin, integrin, keratin or plakin deficiency. Assessment criteria for severe EB:
  • Documented collagen, laminin, integrin, keratin or plakin deficiency (by immunofluorescence staining with protein specific antibodies or Western blotting and by mutation analysis)
  • Adequate Organ Function Criteria
  • Renal: glomerular filtration rate within normal range for age
  • Hepatic: bilirubin, aspartate aminotransferase/alanine aminotransferase (AST/ALT), Alkaline phosphatase (ALP) < 5 x upper limit of normal
  • Pulmonary: adequate pulmonary function in the opinion of the enrolling investigator
Show all 27Show fewer
  • Cardiac: left ventricular ejection fraction ≥ 45%, normal electrocardiogram (EKG) or approved by Cardiology for transplant.
  • Available Healthy HSC Donor (order of preference)
  • Related Donor (marrow or UCB)
  • HLA-A, B, C, DRB1 genotypic identical (sibling) donor
  • HLA-A, B, C, DRB1 phenotypic identical donor
  • 7/8 HLA matched donor at HLA-A, B, C, DRB1
  • Unrelated Donor
  • Marrow
  • HLA-A, B, C, DRB1 phenotypic identical donor
  • 7/8 HLA matched donor at HLA-A, B, C, DRB1
  • UCB
  • HLA-A, B (antigen level) and DRB1 (allele level) matched donor
  • 5/6 HLA matched donor at HLA-A, B, DRB1
  • 4/6 HLA matched donor at HLA-A, B, DRB1
  • Voluntary written consent
  • Absence of Exclusion Criteria:
  • Active systemic infection at time of transplantation (including active infection with Aspergillus or other mold within 30 days).
  • History of human immunodeficiency virus (HIV) infection
  • Evidence of squamous cell carcinoma
  • Donor has EB
  • Pregnancy females of child-bearing age must have a documented negative pregnancy test and agree to use contraception as a condition for enrollment.

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Minnesota Masonic Cancer Center and Medical Center

    Minneapolis, Minnesota, 55455

Other trials in United States

About this study

Official title: MT2009-09: Biochemical Correction of Severe Epidermolysis Bullosa by Allogeneic Stem Cell Transplantation and "Off-the-shelf" Mesenchymal Stem Cells

This is an open-label, single institution, phase II study in patients with epidermolysis bullosa (EB). The underlying hypothesis is that the infusion of bone marrow or umbilical cord blood from a healthy unaffected donor will correct the collagen, laminin, integrin, or plakin deficiency and reduce the skin fragility characteristic of severe forms of EB. A secondary hypothesis is that mesenchymal stem cells from a healthy donor will enhance the safety and efficacy of the allogeneic hematopoietic stem cell transplant as well as serve as a source of renewable cells for the treatment of focal areas of residual blistering.

Read the detailed description

The primary objective of this study is to estimate the event-free survival rate by 1 year post-transplant with an event defined as a death or failure to have a demonstrable increase in collagen, laminin, integrin, keratin or plakin deposition by 1 year post-transplant or other biochemical, structural or physical measure of improvement.

The secondary objectives of this study are to i) determine the incidence of transplant-related mortality (TRM) at 180 days; ii) describe the pattern of biochemical improvement as measured by an increase in protein expression (collagen, laminin, integrin, keratin or plakin) and related structural and physical changes; iii) describe health quality of life at day 365 and 730 as compared to pretreatment results; iv) describe the pattern and durability of HSC and third party MSC engraftment in the skin; v) determine the probability of survival at 1 year.

Patients with severe epidermolysis bullosa will be screened to meet the eligibility requirements, related or unrelated donor marrow or UCB will be infused, and subjects will be followed for a minimum of 5 years after stem cell transplant. A target accrual of 75 subjects over 5 years will be recruited to the study.

Being tested
Cyclophosphamide, Fludarabine, Anti-thymocyte globulin, Myeloablative Busulfan, Mesenchymal stem cell transplantation
Medical subject headings
Epidermolysis Bullosa

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CyclophosphamideDrug

    Also called Cytoxan

    Cyclophosphamide 50 mg/kg/day IV over 2 hours x 1 day, total dose 50 mg/kg will be administered on Day -6.

  • FludarabineDrug

    Also called Fludara

    40 mg/m^2/day intravenously on Days -6, -5, -4, -3 and -2.

  • Anti-thymocyte globulinDrug

    Also called ATG

    30 mg/kg on Days -4, -3 and -2.

  • Myeloablative BusulfanDrug

    Targeting AUC 1000 umol/min

  • Mesenchymal stem cell transplantationProcedure or surgery

    Also called MSCT

    infused via intravenous drip on Day 0

  • Total body irradiationRadiation

    300 cGY on Day -1 administered in a single fraction at a dose rate of 10-19 cGy/minute prescribed to the midplane of the patient at the level of the umbilicus.

  • Bone marrow or umbilical cord blood (UCG) stem cell transplantationProcedure or surgery

    Also called UCBSCT

    Bone marrow or UCB products will be infused as soon as the product arrives and within 30 minutes. The product is infused via IV drip.

Study groups in NCT01033552
Study groupRoleWhat they receive
RDEB MacExperimentalRecessive Dystrophic EB (RDEB) - Myeloablative conditioning (MAC) Participants receive Myeloablative Busulfan (targeting AUC 1000 umol/min), Fludarabine 75 mg/m2, and Cyclophosphamide 200 mg/kg
Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Myeloablative Busulfan; Procedure: Mesenchymal stem cell transplantation; Procedure: Bone marrow or umbilical cord blood (UCG) stem cell transplantation
RDEB RICExperimentalRecessive Dystrophic EB (RDEB) - Reduced Intensity Condition Participants received Fludarabine 500 mg/m2, Cyclosphosphamide 50 mg/kg, equine Anti-thymocyte globulin 90 mg/kg, and low dose total body irradiation (either 200 or 300 cGy)
Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Anti-thymocyte globulin; Procedure: Mesenchymal stem cell transplantation; Radiation: Total body irradiation; Procedure: Bone marrow or umbilical cord blood (UCG) stem cell transplantation
JEB MACExperimentalJunctional EB (JEB) - Myeloablative conditioning (MAC) Participants receive Myeloablative Busulfan (targeting AUC 1000 umol/min), Fludarabine 75 mg/m2, and Cyclophosphamide 200 mg/kg
Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Myeloablative Busulfan; Procedure: Mesenchymal stem cell transplantation; Procedure: Bone marrow or umbilical cord blood (UCG) stem cell transplantation
JEB RICExperimentalJunctional EB (JEB) - Reduced Intensity Condition Participants received Fludarabine 500 mg/m2, Cyclosphosphamide 50 mg/kg, equine Anti-thymocyte globulin 90 mg/kg, and low dose total body irradiation (either 200 or 300 cGy)
Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Anti-thymocyte globulin; Procedure: Mesenchymal stem cell transplantation; Radiation: Total body irradiation; Procedure: Bone marrow or umbilical cord blood (UCG) stem cell transplantation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Event-free Survival

    Event-free survival rate, with an event defined as death or failure to have a demonstrable increase in collagen, laminin, intergrin, keratin or plakin deposition. Assessed at follow up appointments through questionnaire and patient samples.

    Measured: 1 year and 2 Years Post-transplant

Secondary outcomes (6)

  1. Percentage of Participants Transplant-related Mortality (TRM)

    Incidence of transplant-related mortality (TRM)

    Measured: 180 Days Post Transplant

  2. Average Biochemical Improvement

    Pattern of biochemical improvement measured by cumulative increase in protein expression and related structural and physical changes

    Measured: 1 Year Post-Transplant

  3. Measure Patients Quality of Life Using a Questionnaire

    Health quality of life questionnaire as compared to pretreatment results. Scores can range from 0 to 100. The QOLS scores are summed so that a higher score indicates higher quality of life.

    Measured: Pretreatment and 1 year

  4. Durability of HSC Donor Engraftment in the Skin

    Incidence of HSC donor engraftment in the skin

    Measured: 100 Days

  5. Probability of Survival

    Surviving patients one year after engraftment

    Measured: 1 Year

  6. Percentage of Participants Who Experienced Acute GVHD

    Incidence of acute GCHD

    Measured: 100 Days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Dec 2009 (estimated)
  2. Study startJan 2010
  3. Primary completion12 Aug 2021
  4. Study completion12 Aug 2021

Resources

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01033552
Sponsor's protocol ID
MT2009-09
Other IDs
0911M74035
Status last verified
Mar 2024
First submitted
14 Dec 2009
Last updated
3 Apr 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cyclophosphamide, Fludarabine and Anti-thymocyte globulin 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 27 inclusion and 0 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: finished, as of the sponsor's last update on 3 Apr 2024. 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.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Apr 2024). 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?

Percentage of Participants With Event-free Survival (time frame: 1 year and 2 Years 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 NCT01033552.

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 3 Apr 2024.

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