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Trial record 4 of 10 for:    minnesota | epidermolysis bullosa
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Biochemical Correction of Severe EB by Allo HSCT and "Off-the-shelf" MSCs

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ClinicalTrials.gov Identifier: NCT01033552
Recruitment Status : Recruiting
First Posted : December 16, 2009
Last Update Posted : November 13, 2020
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Study Description
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Brief 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 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.

Condition or disease Intervention/treatment Phase
Epidermolysis Bullosa Drug: Cyclophosphamide Drug: Fludarabine Drug: Anti-thymocyte globulin Drug: Cyclosporine A Drug: Mycophenolate mofetil Procedure: Mesenchymal stem cell transplantation Radiation: Total body irradiation Procedure: Bone marrow or umbilical cord blood (UCG) stem cell transplantation Phase 2

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: MT2009-09: Biochemical Correction of Severe Epidermolysis Bullosa by Allogeneic Stem Cell Transplantation and "Off-the-shelf" Mesenchymal Stem Cells
Actual Study Start Date : January 2010
Estimated Primary Completion Date : October 2021
Estimated Study Completion Date : October 2021

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Arms and Interventions
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Arm Intervention/treatment
Experimental: Transplant in Epidermolysis Bullosa Drug: Cyclophosphamide
Cyclophosphamide 50 mg/kg/day IV over 2 hours x 1 day, total dose 50 mg/kg will be administered on Day -6.
Other Name: Cytoxan

Drug: Fludarabine
40 mg/m^2/day intravenously on Days -6, -5, -4, -3 and -2.
Other Name: Fludara

Drug: Anti-thymocyte globulin
30 mg/kg on Days -4, -3 and -2.
Other Name: ATG

Drug: Cyclosporine A
Days -3 to 100+ to maintain a level of >200 ng/ml; initial dose 2.5 mg/kg over 2 hours every 8-12 hours for children.
Other Name: CSA

Drug: Mycophenolate mofetil
15 mg/kg intravenous twice per day on days -3 through 30.
Other Name: CellCept(R)

Procedure: Mesenchymal stem cell transplantation
infused via intravenous drip on Day 0
Other Name: MSCT

Radiation: Total body irradiation
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.

Procedure: Bone marrow or umbilical cord blood (UCG) stem cell transplantation
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.
Other Name: UCBSCT


Outcome Measures
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Primary Outcome Measures :
  1. Event-free survival rate [ Time Frame: 1 year and 2 Years Post-transplant ]
    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.


Secondary Outcome Measures :
  1. Transplant-related mortality (TRM) [ Time Frame: 180 Days Post Transplant ]
    Incidence of transplant-related mortality (TRM)

  2. Pattern of biochemical improvement [ Time Frame: Through 1 Year Post-Transplant ]
    Describe pattern of biochemical improvement as measured by an increase in protein expression (collagen, laminin, integrin, keratin, or plakin) and related structural and physical changes

  3. Quality of Life [ Time Frame: Pretreatment, Day 100, 6 months, 1 and 2 years ]
    Health quality of life questionnaire or iscorEB as compared to pretreatment results

  4. Durability of HSC and third party MSC engraftment in the skin [ Time Frame: 100 Days ]
    Incidence of HSC and third party MSC engraftment in the skin

  5. Probability of Survival [ Time Frame: 1 Year ]
    Number of surviving patients one year after engraftment

  6. Number of participants experiencing Acute GVHD [ Time Frame: 100 Days ]
    Incidence of acute GCHD


Eligibility Criteria
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Ages Eligible for Study:   up to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
    • 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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01033552


Contacts
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Contact: Kim Nelson, RN 612-273-2925 knelso62@fairview.org

Locations
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United States, Minnesota
University of Minnesota Masonic Cancer Center and Medical Center Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Kim Nelson, RN    612-273-2925    knelso62@fairview.org   
Principal Investigator: Jakub Tolar, MD, PhD         
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
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Principal Investigator: Jakub Tolar, MD, PhD Masonic Cancer Center, University of Minnesota
More Information
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Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT01033552    
Other Study ID Numbers: MT2009-09
0911M74035 ( Other Identifier: IRB, University of Minnesota )
First Posted: December 16, 2009    Key Record Dates
Last Update Posted: November 13, 2020
Last Verified: November 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Additional relevant MeSH terms:
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Epidermolysis Bullosa
Skin Abnormalities
Congenital Abnormalities
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases
Skin Diseases, Vesiculobullous
Cyclosporine
Mycophenolic Acid
Cyclophosphamide
Fludarabine
Cyclosporins
Antilymphocyte Serum
Immunosuppressive Agents
Immunologic Factors
 Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Enzyme Inhibitors
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Calcineurin Inhibitors
Antibiotics, Antineoplastic
Antibiotics, Antitubercular
Antitubercular Agents