Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02582775
Recruitment Status : Recruiting
First Posted : October 21, 2015
Last Update Posted : September 25, 2018
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Tracking Information
First Submitted Date  ICMJE October 16, 2015
First Posted Date  ICMJE October 21, 2015
Last Update Posted Date September 25, 2018
Study Start Date  ICMJE March 2016
Estimated Primary Completion Date September 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 5, 2016)
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
Original Primary Outcome Measures  ICMJE
 (submitted: October 19, 2015)
Event-free survival [ Time Frame: 1 year post-transplant ]
Change History Complete list of historical versions of study NCT02582775 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 15, 2017)
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 19, 2015)
  • Percentage change of a patient's IScoreEB [ Time Frame: Day 60 post-transplant ]
  • Percentage change of a patient's IScoreEB [ Time Frame: Day 100 post-transplant ]
  • Percentage change of a patient's IScoreEB [ Time Frame: Day 180 post-transplant ]
  • Percentage change of a patient's IScoreEB [ Time Frame: 1 year post-transplant ]
  • Percentage change of a patient's IScoreEB [ Time Frame: 2 years post-transplant ]
  • 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.
  • Biochemical improvement [ Time Frame: Day 28 post-transplant ]
    Measured by protein expression
  • Biochemical improvement [ Time Frame: Day 60 post-transplant ]
    Measured by protein expression
  • Biochemical improvement [ Time Frame: Day 100 post-transplant ]
    Measured by protein expression
  • Biochemical improvement [ Time Frame: Day 180 post-transplant ]
    Measured by protein expression
  • Biochemical improvement [ Time Frame: 1 year post-transplant ]
    Measured by protein expression
  • Biochemical improvement [ Time Frame: 2 years post-transplant ]
    Measured by protein expression
  • Quality of life [ Time Frame: Day 100 post-transplant ]
    Measured by the Lansky score (10-100)
  • Quality of life [ Time Frame: 1 year post-transplant ]
    Measured by the Lansky score (10-100)
  • Quality of life [ Time Frame: 2 years post-transplant ]
    Measured by the Lansky score (10-100)
  • Durability of HSC and donor MSC engraftment [ Time Frame: Day 28 post-transplant ]
    Histological changes will be assessed with light microscopy and the expression of C7 with a panel of anti-C7 antibodies; ultrastructural changes assessed with transmission electron microscopy and presence of C7-containing anchoring fibrils with immuno-electron microscopy; and donor engraftment in skin assessed by competitive polymerase-chain-reaction analysis of polymorphic variable-number tandem-repeat regions.
  • Durability of HSC and donor MSC engraftment [ Time Frame: Day 60 post-transplant ]
    Histological changes will be assessed with light microscopy and the expression of C7 with a panel of anti-C7 antibodies; ultrastructural changes assessed with transmission electron microscopy and presence of C7-containing anchoring fibrils with immuno-electron microscopy; and donor engraftment in skin assessed by competitive polymerase-chain-reaction analysis of polymorphic variable-number tandem-repeat regions.
  • Durability of HSC and donor MSC engraftment [ Time Frame: Day 100 post-transplant ]
    Histological changes will be assessed with light microscopy and the expression of C7 with a panel of anti-C7 antibodies; ultrastructural changes assessed with transmission electron microscopy and presence of C7-containing anchoring fibrils with immuno-electron microscopy; and donor engraftment in skin assessed by competitive polymerase-chain-reaction analysis of polymorphic variable-number tandem-repeat regions.
  • Durability of HSC and donor MSC engraftment [ Time Frame: Day 180 post-transplant ]
    Histological changes will be assessed with light microscopy and the expression of C7 with a panel of anti-C7 antibodies; ultrastructural changes assessed with transmission electron microscopy and presence of C7-containing anchoring fibrils with immuno-electron microscopy; and donor engraftment in skin assessed by competitive polymerase-chain-reaction analysis of polymorphic variable-number tandem-repeat regions.
  • Durability of HSC and donor MSC engraftment [ Time Frame: 1 year post-transplant ]
    Histological changes will be assessed with light microscopy and the expression of C7 with a panel of anti-C7 antibodies; ultrastructural changes assessed with transmission electron microscopy and presence of C7-containing anchoring fibrils with immuno-electron microscopy; and donor engraftment in skin assessed by competitive polymerase-chain-reaction analysis of polymorphic variable-number tandem-repeat regions.
  • Durability of HSC and donor MSC engraftment [ Time Frame: 2 years post-transplant ]
    Histological changes will be assessed with light microscopy and the expression of C7 with a panel of anti-C7 antibodies; ultrastructural changes assessed with transmission electron microscopy and presence of C7-containing anchoring fibrils with immuno-electron microscopy; and donor engraftment in skin assessed by competitive polymerase-chain-reaction analysis of polymorphic variable-number tandem-repeat regions.
  • Donor Chimerism in the Skin [ Time Frame: Day 28 post-transplant ]
    Donor engraftment in skin assessed by competitive polymerase-chain-reaction analysis of polymorphic variable-number tandem-repeat regions.
  • Donor Chimerism in the Skin [ Time Frame: Day 60 post-transplant ]
    Donor engraftment in skin assessed by competitive polymerase-chain-reaction analysis of polymorphic variable-number tandem-repeat regions.
  • Donor Chimerism in the Skin [ Time Frame: Day 100 post-transplant ]
    Donor engraftment in skin assessed by competitive polymerase-chain-reaction analysis of polymorphic variable-number tandem-repeat regions.
  • Donor Chimerism in the Skin [ Time Frame: Day 180 post-transplant ]
    Donor engraftment in skin assessed by competitive polymerase-chain-reaction analysis of polymorphic variable-number tandem-repeat regions.
  • Donor Chimerism in the Skin [ Time Frame: 1 year post-transplant ]
    Donor engraftment in skin assessed by competitive polymerase-chain-reaction analysis of polymorphic variable-number tandem-repeat regions.
  • Donor Chimerism in the Skin [ Time Frame: 2 years post-transplant ]
    Donor engraftment in skin assessed by competitive polymerase-chain-reaction analysis of polymorphic variable-number tandem-repeat regions.
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE MT2015-20: Biochemical Correction of Severe EB by Allo HSCT and Serial Donor MSCs
Official Title  ICMJE MT2015-20: Biochemical Correction of Severe Epidermolysis Bullosa by Allogeneic Cell Transplantation and Serial Donor Mesenchymal Cell Infusions
Brief Summary 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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Epidermolysis Bullosa
Intervention  ICMJE
  • 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)
Study Arms
  • 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.
    Interventions:
    • Drug: Thymoglobulin
    • Drug: Cyclophosphamide
    • Drug: Fludarabine
    • Radiation: Total Body Irradiation
    • Procedure: Bone marrow infusion
    • Drug: Tacrolimus
    • Drug: Mycophenolate Mofetil
  • 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.
    Interventions:
    • 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
  • 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.
    Interventions:
    • Drug: Thymoglobulin
    • Drug: Cyclophosphamide
    • Drug: Fludarabine
    • Radiation: Total Body Irradiation
    • Procedure: Bone marrow infusion
    • Drug: Tacrolimus
    • Drug: Mycophenolate Mofetil
  • 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).
    Interventions:
    • Drug: Thymoglobulin
    • Drug: Cyclophosphamide
    • Drug: Fludarabine
    • Radiation: Total Body Irradiation
    • Procedure: Bone marrow infusion
    • Drug: Tacrolimus
    • Drug: Mycophenolate Mofetil
  • 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)
    Interventions:
    • 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
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 19, 2015)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date September 2022
Estimated Primary Completion Date September 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender
Sexes Eligible for Study: All
Ages up to 25 Years   (Child, Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE
Contact: Kim Nelson, RN 612-273-2925 knelso62@fairview.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02582775
Other Study ID Numbers  ICMJE 2015LS076
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party Masonic Cancer Center, University of Minnesota
Study Sponsor  ICMJE Masonic Cancer Center, University of Minnesota
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jakub Tolar, MD, PhD Masonic Cancer Center, University of Minnesota
PRS Account Masonic Cancer Center, University of Minnesota
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP