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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02582775
Other study ID # 2015LS076
Secondary ID
Status Completed
Phase Phase 2
First received
Last updated
Start date March 2016
Est. completion date July 26, 2023

Study information

Verified date July 2023
Source Masonic Cancer Center, University of Minnesota
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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).


Recruitment information / eligibility

Status Completed
Enrollment 17
Est. completion date July 26, 2023
Est. primary completion date November 15, 2022
Accepts healthy volunteers No
Gender All
Age group N/A to 25 Years
Eligibility 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 Design


Related Conditions & MeSH terms


Intervention

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
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
Fludarabine
30 mg/m2 IV over 60 minutes days -6 through day -2
Radiation:
Total Body Irradiation
See arm description for dosing.
Procedure:
Bone marrow infusion
Bone marrow infusion on Day 0
Drug:
Tacrolimus
Day +5 through day +100 with goals of 5-10 ug/L (not used for HLA-identical related donors)
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
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)

Locations

Country Name City State
United States University of Minnesota Masonic Cancer Center and Medical Center Minneapolis Minnesota

Sponsors (1)

Lead Sponsor Collaborator
Masonic Cancer Center, University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Event-free survival An event defined as death or a 50% increase in a patient's IScoreEB from baseline 1 year post-transplant
Secondary Percentage change of a patient's iscorEB 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
Secondary Transplant-related mortality 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
Secondary Quality of life Measured by the Lansky or Karnofsky score (10-100) 1 year post-transplant
Secondary Quality of life Measured by the Lansky or Karnofsky score (10-100) 2 years post-transplant
Secondary Lymphoid Chimerism Proportion of lymphoid chimerism at various time-points. Day 28, 60, 100, 180, and year 1 and 2 post-transplant
Secondary Myeloid Chimerism Proportion of myeloid chimerism at various time points. Day 28, 60, 100, 180, and year 1 and 2 post-transplant
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