Clinical trial NCT02582775: MT2015-20: Biochemical Correction of Severe EB by Allo HSCT and Serial Donor MSCs
Official title: MT2015-20: Biochemical Correction of Severe Epidermolysis Bullosa by Allogeneic Cell Transplantation and Serial Donor Mesenchymal Cell Infusions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Epidermolysis Bullosa
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2015-10-21
Enrollment: 17
Sex: ALL
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility 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.

Primary outcomes:
measure: Event-free Survival
timeFrame: 1 year post-transplant
Secondary outcomes:
measure: Change of a Patient's iscorEB
timeFrame: 1 year post-transplant
measure: Transplant-related Mortality
timeFrame: 180 days post-transplant
measure: Average Change in Quality of Life
timeFrame: 1 year post-transplant
measure: Average Change in Quality of Life
timeFrame: 2 years post-transplant
measure: Lymphoid Chimerism
timeFrame: Day 28, 60, 100, 180, and year 1 and 2 post-transplant
measure: Myeloid Chimerism
timeFrame: Day 28, 60, 100, 180, and year 1 and 2 post-transplant
measure: Average Change of a Patient's iscorEB
timeFrame: 2 year post-transplant
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota Masonic Cancer Center and Medical Center
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Jakub Tolar, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ebens CL, McGrath JA, Tamai K, Hovnanian A, Wagner JE, Riddle MJ, Keene DR, DeFor TE, Tryon R, Chen M, Woodley DT, Hook K, Tolar J. Bone marrow transplant with post-transplant cyclophosphamide for recessive dystrophic epidermolysis bullosa expands the related donor pool and permits tolerance of nonhaematopoietic cellular grafts. Br J Dermatol. 2019 Dec;181(6):1238-1246. doi: 10.1111/bjd.17858. Epub 2019 Jun 28.