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

July 31, 2023 updated by: Masonic Cancer Center, University of Minnesota

MT2015-20: Biochemical Correction of Severe Epidermolysis Bullosa by Allogeneic Cell Transplantation and Serial Donor Mesenchymal Cell Infusions

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

17

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota Masonic Cancer Center and Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 25 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CLOSED TO ACCRUAL 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 Names:
  • Cytoxan
Drug: Fludarabine
30 mg/m2 IV over 60 minutes days -6 through day -2
Other Names:
  • Fludara
  • fludarabine phosphate
Radiation: Total Body Irradiation
See arm description for dosing.
Other Names:
  • TBI
Procedure: Bone marrow infusion
Bone marrow infusion on Day 0
Other Names:
  • HCT
Drug: Tacrolimus
Day +5 through day +100 with goals of 5-10 ug/L (not used for HLA-identical related donors)
Other Names:
  • 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 Names:
  • MMF
Experimental: CLOSED TO ACCRUAL 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 Names:
  • Cytoxan
Drug: Fludarabine
30 mg/m2 IV over 60 minutes days -6 through day -2
Other Names:
  • Fludara
  • fludarabine phosphate
Radiation: Total Body Irradiation
See arm description for dosing.
Other Names:
  • TBI
Procedure: Bone marrow infusion
Bone marrow infusion on Day 0
Other Names:
  • HCT
Drug: Tacrolimus
Day +5 through day +100 with goals of 5-10 ug/L (not used for HLA-identical related donors)
Other Names:
  • 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 Names:
  • 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 Names:
  • Cytoxan
Drug: Fludarabine
30 mg/m2 IV over 60 minutes days -6 through day -2
Other Names:
  • Fludara
  • fludarabine phosphate
Radiation: Total Body Irradiation
See arm description for dosing.
Other Names:
  • TBI
Procedure: Bone marrow infusion
Bone marrow infusion on Day 0
Other Names:
  • HCT
Drug: Tacrolimus
Day +5 through day +100 with goals of 5-10 ug/L (not used for HLA-identical related donors)
Other Names:
  • 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 Names:
  • MMF
Biological: Donor mesenchymal stem cell infusions
Day 60, 100 and 180 (collected during donor BM harvest for graft)
Experimental: Arm D: HCT with 200 cGy BID of TBI
HLA-matched 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 Names:
  • Cytoxan
Drug: Fludarabine
30 mg/m2 IV over 60 minutes days -6 through day -2
Other Names:
  • Fludara
  • fludarabine phosphate
Radiation: Total Body Irradiation
See arm description for dosing.
Other Names:
  • TBI
Procedure: Bone marrow infusion
Bone marrow infusion on Day 0
Other Names:
  • HCT
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 Names:
  • MMF
Experimental: Arm E: HCT plus MSC, 200 cGy BID of TBI
HLA-matched 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 Names:
  • Cytoxan
Drug: Fludarabine
30 mg/m2 IV over 60 minutes days -6 through day -2
Other Names:
  • Fludara
  • fludarabine phosphate
Radiation: Total Body Irradiation
See arm description for dosing.
Other Names:
  • TBI
Procedure: Bone marrow infusion
Bone marrow infusion on Day 0
Other Names:
  • HCT
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 Names:
  • MMF
Biological: Donor mesenchymal stem cell infusions
Day 60, 100 and 180 (collected during donor BM harvest for graft)
Experimental: Arm F: HCT Alone, 200 cGy BID of TBI
HLA-mismatched epidermolysis bullosa patients treated with hematopoietic cell transplant alone using 200 cGy BID of TBI (400 cGy total) + addition of low dose busulfan for recipients of HLA-mismatched bone marrow
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 Names:
  • Cytoxan
Drug: Fludarabine
30 mg/m2 IV over 60 minutes days -6 through day -2
Other Names:
  • Fludara
  • fludarabine phosphate
Radiation: Total Body Irradiation
See arm description for dosing.
Other Names:
  • TBI
Procedure: Bone marrow infusion
Bone marrow infusion on Day 0
Other Names:
  • HCT
Drug: Tacrolimus
Day +5 through day +100 with goals of 5-10 ug/L (not used for HLA-identical related donors)
Other Names:
  • 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 Names:
  • MMF
Drug: Busulfan
busulfan IV over 3 hours on days -3 and -2 for HLA-mismatched BM recipients only (Arms F and G)
Experimental: Arm G: HCT plus MSC, 200 cGy
HLA-mismatched epidermolysis bullosa patients treated with hematopoietic cell transplant plus serial MSC infusions using 200 cGy BID of TBI (400 cGy total) + addition of low dose busulfan for recipients of HLA-mismatched bone marrow
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 Names:
  • Cytoxan
Drug: Fludarabine
30 mg/m2 IV over 60 minutes days -6 through day -2
Other Names:
  • Fludara
  • fludarabine phosphate
Radiation: Total Body Irradiation
See arm description for dosing.
Other Names:
  • TBI
Procedure: Bone marrow infusion
Bone marrow infusion on Day 0
Other Names:
  • HCT
Drug: Tacrolimus
Day +5 through day +100 with goals of 5-10 ug/L (not used for HLA-identical related donors)
Other Names:
  • 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 Names:
  • MMF
Biological: Donor mesenchymal stem cell infusions
Day 60, 100 and 180 (collected during donor BM harvest for graft)
Drug: Busulfan
busulfan IV over 3 hours on days -3 and -2 for HLA-mismatched BM recipients only (Arms F and G)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
1 year post-transplant

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
1 and 2 year 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.
180 days post-transplant
Quality of life
Time Frame: 1 year post-transplant
Measured by the Lansky or Karnofsky score (10-100)
1 year post-transplant
Quality of life
Time Frame: 2 years post-transplant
Measured by the Lansky or Karnofsky score (10-100)
2 years post-transplant
Lymphoid Chimerism
Time Frame: Day 28, 60, 100, 180, and year 1 and 2 post-transplant
Proportion of lymphoid chimerism at various time-points.
Day 28, 60, 100, 180, and year 1 and 2 post-transplant
Myeloid Chimerism
Time Frame: Day 28, 60, 100, 180, and year 1 and 2 post-transplant
Proportion of myeloid chimerism at various time points.
Day 28, 60, 100, 180, and year 1 and 2 post-transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Masonic Cancer Center, University of Minnesota

Investigators

  • Principal Investigator: Jakub Tolar, MD, PhD, Masonic Cancer Center, University of Minnesota

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2016

Primary Completion (Actual)

November 15, 2022

Study Completion (Actual)

July 26, 2023

Study Registration Dates

First Submitted

October 16, 2015

First Submitted That Met QC Criteria

October 19, 2015

First Posted (Estimated)

October 21, 2015

Study Record Updates

Last Update Posted (Actual)

August 1, 2023

Last Update Submitted That Met QC Criteria

July 31, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2015LS076

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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