LYell SYndrome MEsenchymal Stromal Cells Treatment

Study Overview
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Brief Summary
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Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare severe cutaneous adverse reactions (SCARs) to drugs. To date, no curative drug has demonstrated with a good level of evidence its ability to promote SJS and TEN healing and could contribute to earlier reepithelialisation. Mesenchymal stroma cells (MSCs) therapy represents a new therapeutic approach. eg, in patients with cardiovascular diseases, neurological diseases, renal transplantation, lung diseases as acute respiratory distress syndrome. Recently, MSCs have been proposed in both burn wound healing with a significantly decrease of the unhealed burn area and in cutaneous radiation. Moreover, MSCs have immunomodulation properties potentially effective in refractory acute and chronic graft versus host disease (GVHD) by improving thymic function and induction of Tregs. Indeed, MSCs are able to migrate to inflamed tissues after stimulation by pro-inflammatory cytokines and to modulate the local inflammatory reactions. MSCs have also demonstrated their ability to promote tissue remodelling, angiogenesis and immunomodulation through either differentiation or secretion of several growth factors such as VEGF, basic FGF and various cytokines. Therefore, combining their immunomodulation effect and secretion of soluble factors involved in wound repair, MSCs might be valuable as a cell therapy strategy for promoting cutaneous healing in SJS-TEN syndrome and subsequently decrease the morbi-mortality.

Official Title
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Mesenchymal Stromal Cells Treatment in Lyell Syndrome: A Pilot Phase 1-2 Open Trial

Conditions
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Epidermal Necrolysis, Lyell Syndrome, Toxic Epidermal Necrolysis, Overlap Syndrome, Mesenchymal Stromal Cells, Adipose Derived Stromal Cells

Intervention / Treatment
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* Drug: Adipose derived stromal cells intravenously injected


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged from 18 to 75 years-old Admission less than 10 days after onset of the reaction Patient with confirmed SJS-TEN diagnosis hospitalized in the department of Dermatology or intensive care medicine At least 10 % of detachable-detached body surface area at any time during the first 10 days after the index date (date of the first symptoms of the disease) Written consent from patient or trustworthy person or legal representant or family member Affiliated to a social security scheme Exclusion Criteria: Pregnant or breastfeeding women History of malignant disease within the past ten years and or presence of metastasis Positive serology for HIV Active infection for hepatitis B or C Decompensated cardiac failure Uncontrolled epilepsia Previous history of allogenic bone marrow transplantation Participation in other interventional drug research Patient deprived of liberty by a judicial or administrative decision or under the protection of justice Any psychological, familial, sociological or geographical condition potentially hampering compliance with the research protocol and follow-up schedule Patient under tutorship or curatorship Patient under psychiatric care according to art. L1121-6 CSP

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adipose derived stromal cells intravenously injected<br> | Drug: Adipose derived stromal cells intravenously injected<br>* 2×10^6/kg of Adipose derived stromal cells A single injection at D0 (performed maximum three days post-admission).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety : Observation of at least one adverse effect |  | Day 10 | 
| Efficacy : Rate of complete or almost complete reepithelialisation |  | Day 7 after infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of observed and predicted death by the SCORTEN |  | at one month | 
| Duration of hospitalisation according to our historical cohort related to BSA involved |  | Month 12 | 
| Duration of hospitalisation according to our historical cohort related to onset of the disease |  | Month 12 | 
| Duration of hospitalisation according to our historical cohort related to SCORTEN |  | Month 12 | 
| Duration of each mucous membranes healing ie.(buccal, nasal, genital, eyes) |  | at Month 12 | 
| Rate of sepsis |  | at Month 12 | 
| Rate of intensive care transfer |  | at Month 12 | 
| Rate of sequelae |  | at Month 12 | 
| Th1/Th2 immune response in the peripheral blood of the patients |  | after injection at Day 0, Day 10, Month 1 | 
| Evaluation of expression profile of Th1/Th2 associated chemokines and anti-inflammatory chemokines in the peripheral blood |  | after injection at Day 0, Day 10, Month 1. | 
| Epidermal chimerism study on healed skin biopsy |  | at 1 month | 
| Cutaneous re-epithelialization rate at D5, D10 and D15 post-infusion according to the percentage of cutaneous BSA re-epithelialized in comparison to maximal cutaneous detachable-detached BSA observed. |  | at Day 5, Day 10 and Day15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epidermal necrolysis, Lyell syndrome, toxic epidermal necrolysis, Overlap syndrome, Mesenchymal stromal cells, Adipose derived stromal cells