LYSYME: LYell SYndrome MEsenchymal Stromal Cells Treatment

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04711200

Collaborator

(none)

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Epidermal Necrolysis Lyell Syndrome Toxic Epidermal Necrolysis Overlap Syndrome Mesenchymal Stromal Cells Adipose Derived Stromal Cells	Drug: Adipose derived stromal cells intravenously injected	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

15 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Sep 1, 2022

Anticipated Primary Completion Date :

Sep 1, 2025

Anticipated Study Completion Date :

Sep 1, 2025

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Adipose derived stromal cells intravenously injected

Drug: Adipose derived stromal cells intravenously injected

2×10^6/kg of Adipose derived stromal cells A single injection at D0 (performed maximum three days post-admission).

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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