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MT2015-20: Biochemical Correction of Severe EB by Allo HSCT and Serial Donor MSCs

This study is currently recruiting participants.
See Contacts and Locations
Verified June 2017 by Masonic Cancer Center, University of Minnesota
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT02582775
First received: October 16, 2015
Last updated: June 15, 2017
Last verified: June 2017
  Purpose
This is a single-institution, phase II study to determine the event-free survival at 1 year post allogeneic transplant and serial mesenchymal stem cell (MSC) infusions from a related donor (HLA identical, mismatched or haploidentical) or matched unrelated donor for the biochemical correction of severe epidermolysis bullosa (EB).

Condition Intervention Phase
Epidermolysis Bullosa Drug: Thymoglobulin Drug: Cyclophosphamide Drug: Fludarabine Radiation: Total Body Irradiation Procedure: Bone marrow infusion Drug: Tacrolimus Drug: Mycophenolate Mofetil Biological: Donor mesenchymal stem cell infusions Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: MT2015-20: Biochemical Correction of Severe Epidermolysis Bullosa by Allogeneic Cell Transplantation and Serial Donor Mesenchymal Cell Infusions

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • Event-free survival [ Time Frame: 1 year post-transplant ]
    An event defined as death or a 50% increase in a patient's IScoreEB from baseline


Secondary Outcome Measures:
  • Percentage change of a patient's iscorEB [ Time Frame: 1 and 2 year post-transplant ]
    iscorEB surveys are a validated, standard of care tool used to assess disease status in patients with Epidermolysis Bullosa.

  • Transplant-related mortality [ Time Frame: 180 days post-transplant ]
    Cumulative incidence will be used to estimate the probability of relapse treating non-relapse death as a competing risk and transplant-related mortality conversely treating relapse as a competing risk.

  • Quality of life [ Time Frame: 1 year post-transplant ]
    Measured by the Lansky or Karnofsky score (10-100)

  • Quality of life [ Time Frame: 2 years post-transplant ]
    Measured by the Lansky or Karnofsky score (10-100)

  • Lymphoid Chimerism [ Time Frame: Day 28, 60, 100, 180, and year 1 and 2 post-transplant ]
    Proportion of lymphoid chimerism at various time-points.

  • Myeloid Chimerism [ Time Frame: Day 28, 60, 100, 180, and year 1 and 2 post-transplant ]
    Proportion of myeloid chimerism at various time points.


Estimated Enrollment: 60
Study Start Date: March 2016
Estimated Study Completion Date: September 2022
Estimated Primary Completion Date: September 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: HCT with 300 cGY of TBI
Epidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant without mesenchymal stem cell infusions.
Drug: Thymoglobulin
0.5 mg/kg IV over 6 hours on day -9 and 2 mg/kg IV over 4 hours on day -8 and day -7 with premeds and solumedrol through day -2
Other Names:
  • ATG
  • anti-thymocyte globulin
Drug: Cyclophosphamide
14.5 mg/kg IV over 1 hour day -6 and -5 50 mg/kg IV over 2 hours with mesna 40 mg/kg IV day +2 and +3
Other Name: Cytoxan
Drug: Fludarabine
30 mg/m2 IV over 60 minutes days -6 through day -2
Other Names:
  • fludarabine phosphate
  • Fludara
Radiation: Total Body Irradiation
See arm description for dosing.
Other Name: TBI
Procedure: Bone marrow infusion
Bone marrow infusion on Day 0
Other Name: HCT
Drug: Tacrolimus
Day +5 through day +100 with goals of 5-10 ug/L (not used for HLA-identical related donors)
Other Name: Prograf
Drug: Mycophenolate Mofetil
15 mg/kg IV q8h (based upon actual body weight) with the maximum total daily dose not to exceed 3 grams. Day +5 through day 35
Other Name: MMF
Experimental: Arm B: HCT plus MSC, 300 cGY of TBI
Epidermolysis bullosa patients treated per study regimen with chemotherapy and hematopoietic stem cell transplant with mesenchymal stem cell infusions using 300 cGY of TBI.
Drug: Thymoglobulin
0.5 mg/kg IV over 6 hours on day -9 and 2 mg/kg IV over 4 hours on day -8 and day -7 with premeds and solumedrol through day -2
Other Names:
  • ATG
  • anti-thymocyte globulin
Drug: Cyclophosphamide
14.5 mg/kg IV over 1 hour day -6 and -5 50 mg/kg IV over 2 hours with mesna 40 mg/kg IV day +2 and +3
Other Name: Cytoxan
Drug: Fludarabine
30 mg/m2 IV over 60 minutes days -6 through day -2
Other Names:
  • fludarabine phosphate
  • Fludara
Radiation: Total Body Irradiation
See arm description for dosing.
Other Name: TBI
Procedure: Bone marrow infusion
Bone marrow infusion on Day 0
Other Name: HCT
Drug: Tacrolimus
Day +5 through day +100 with goals of 5-10 ug/L (not used for HLA-identical related donors)
Other Name: Prograf
Drug: Mycophenolate Mofetil
15 mg/kg IV q8h (based upon actual body weight) with the maximum total daily dose not to exceed 3 grams. Day +5 through day 35
Other Name: MMF
Biological: Donor mesenchymal stem cell infusions
Day 60, 100 and 180 (collected during donor BM harvest for graft)
Experimental: Arm C: Re-Transplant with 300 cGY of TBI
Epidermolysis bullosa patients treated regardless of original transplant arm with re-transplant using 300 cGy of TBI.
Drug: Thymoglobulin
0.5 mg/kg IV over 6 hours on day -9 and 2 mg/kg IV over 4 hours on day -8 and day -7 with premeds and solumedrol through day -2
Other Names:
  • ATG
  • anti-thymocyte globulin
Drug: Cyclophosphamide
14.5 mg/kg IV over 1 hour day -6 and -5 50 mg/kg IV over 2 hours with mesna 40 mg/kg IV day +2 and +3
Other Name: Cytoxan
Drug: Fludarabine
30 mg/m2 IV over 60 minutes days -6 through day -2
Other Names:
  • fludarabine phosphate
  • Fludara
Radiation: Total Body Irradiation
See arm description for dosing.
Other Name: TBI
Procedure: Bone marrow infusion
Bone marrow infusion on Day 0
Other Name: HCT
Drug: Tacrolimus
Day +5 through day +100 with goals of 5-10 ug/L (not used for HLA-identical related donors)
Other Name: Prograf
Drug: Mycophenolate Mofetil
15 mg/kg IV q8h (based upon actual body weight) with the maximum total daily dose not to exceed 3 grams. Day +5 through day 35
Other Name: MMF
Experimental: Arm D: HCT with 200 cGY BID of TBI
Epidermolysis bullosa patients treated with hematopoietic cell transplant alone using 200 cGY BID of TBI (400 cGy total).
Drug: Thymoglobulin
0.5 mg/kg IV over 6 hours on day -9 and 2 mg/kg IV over 4 hours on day -8 and day -7 with premeds and solumedrol through day -2
Other Names:
  • ATG
  • anti-thymocyte globulin
Drug: Cyclophosphamide
14.5 mg/kg IV over 1 hour day -6 and -5 50 mg/kg IV over 2 hours with mesna 40 mg/kg IV day +2 and +3
Other Name: Cytoxan
Drug: Fludarabine
30 mg/m2 IV over 60 minutes days -6 through day -2
Other Names:
  • fludarabine phosphate
  • Fludara
Radiation: Total Body Irradiation
See arm description for dosing.
Other Name: TBI
Procedure: Bone marrow infusion
Bone marrow infusion on Day 0
Other Name: HCT
Drug: Tacrolimus
Day +5 through day +100 with goals of 5-10 ug/L (not used for HLA-identical related donors)
Other Name: Prograf
Drug: Mycophenolate Mofetil
15 mg/kg IV q8h (based upon actual body weight) with the maximum total daily dose not to exceed 3 grams. Day +5 through day 35
Other Name: MMF
Experimental: Arm E: HCT plus MSC, 200 cGY BID of TBI
Epidermolysis bullosa patients treated with hematopoietic cell transplant plus serial MSC infusions using 200 cGY BID of TBI (400 cGy total)
Drug: Thymoglobulin
0.5 mg/kg IV over 6 hours on day -9 and 2 mg/kg IV over 4 hours on day -8 and day -7 with premeds and solumedrol through day -2
Other Names:
  • ATG
  • anti-thymocyte globulin
Drug: Cyclophosphamide
14.5 mg/kg IV over 1 hour day -6 and -5 50 mg/kg IV over 2 hours with mesna 40 mg/kg IV day +2 and +3
Other Name: Cytoxan
Drug: Fludarabine
30 mg/m2 IV over 60 minutes days -6 through day -2
Other Names:
  • fludarabine phosphate
  • Fludara
Radiation: Total Body Irradiation
See arm description for dosing.
Other Name: TBI
Procedure: Bone marrow infusion
Bone marrow infusion on Day 0
Other Name: HCT
Drug: Tacrolimus
Day +5 through day +100 with goals of 5-10 ug/L (not used for HLA-identical related donors)
Other Name: Prograf
Drug: Mycophenolate Mofetil
15 mg/kg IV q8h (based upon actual body weight) with the maximum total daily dose not to exceed 3 grams. Day +5 through day 35
Other Name: MMF
Biological: Donor mesenchymal stem cell infusions
Day 60, 100 and 180 (collected during donor BM harvest for graft)

  Eligibility

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 EB characterized by collagen, laminin, integrin, keratin or plakin deficiency (by immunofluorescence staining with protein specific antibodies or Western blotting and by mutation analysis).
  • Adequate organ function within 4 weeks of study registration defined as:

    • Renal: glomerular filtration rate within normal range for age
    • Hepatic: Hepatic: bilirubin, AST/ALT, 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 EKG or approved by Cardiology for transplant
  • Sexually active participants must agree to use adequate birth control for the during the study period (from before the start of the preparative chemotherapy through 1 year post-transplant)
  • Available donor per section 5: targeted MFI < 1,000 (MFI exceeding 1000 must be approved by the PI and treatment team.)
  • Voluntary written consent - adult or parent (with information sheet for minors, if applicable) prior to any research related procedures or treatment

Exclusion Criteria:

  • beta 3 laminin JEB mutants
  • Active untreated systemic infection at time of transplantation (including active infection with Aspergillus or other mold within 30 days)
  • History of HIV infection
  • Evidence of squamous cell carcinoma
  • Pregnant or breast feeding. Females of child-bearing potential must have a negative pregnancy test prior to study registration as the agents administered in this study are Pregnancy Category C and D.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02582775

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

Locations
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
Principal Investigator: Jakub Tolar, MD, PhD Masonic Cancer Center, University of Minnesota
  More Information

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT02582775     History of Changes
Other Study ID Numbers: 2015LS076
Study First Received: October 16, 2015
Last Updated: June 15, 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Epidermolysis Bullosa
Skin Abnormalities
Congenital Abnormalities
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases
Skin Diseases, Vesiculobullous
Cyclophosphamide
Tacrolimus
Fludarabine phosphate
Mycophenolate mofetil
Antilymphocyte Serum
Fludarabine
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Calcineurin Inhibitors
Enzyme Inhibitors
Antimetabolites, Antineoplastic
Antimetabolites
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on August 22, 2017