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

Epidermolysis Bullosa Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02582775
• Other study ID #: 2015LS076
• Status: Completed
• Phase: Phase 2
• 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
• 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.

Related Conditions & MeSH terms

• Epidermolysis Bullosa

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