MORPHEE : Mechanisms of Cell Death Induced by Extracorporeal Photochemotherapy

Graft Vs Host Disease Clinical Trial

— MORPHEE  

Official title:

MORPHEE : Mechanisms of Cell Death Induced by Extracorporeal Photochemotherapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05333367
• Other study ID #: 2022/679
• Status: Recruiting
• Phase: N/A
• Start date: April 15, 2022
• Est. completion date: July 2023

Study information

• Verified date: April 2022
• Source: Centre Hospitalier Universitaire de Besancon
• Contact: Charline VAUCHY, PhD
• Phone: +33381218875
• Email: cvauchy[@]chu-besancon.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this study is to describe the type of cell death induced by extracorporeal photochemotherapy, depending on the cell type, using a panel of complementary analysis techniques.

Description:

Extracorporeal photochemotherapy (ECP) is a cell therapy used for its immunomodulation and tolerance induction capabilities. Its main indications are the control of graft-versus-host (GVH) disease in hematopoietic cell allografts, treatment and control of rejection in solid organ transplantation and the treatment of cutaneous T-cell lymphoma. Data on the mechanisms of action of ECP remains very patchy. This lack of data limits the discussion on therapeutic regimens by disease.

ECP consists of repeated apheresis sessions to collect leukocytes from the patient. The cells are then photosensitized, irradiated with UVA and reinjected into the patient in a closed circuit. In the context of GVH, induced cell death would stimulate the expansion of regulatory cells (Treg), restore a Th1/Th2 balance and decrease Th17 polarization. The ECP also allows the expansion of Treg in solid organ transplantation. Conversely, ECP would restore or activate an antitumor immune response in cutaneous T lymphoma.

The type of cells collected and treated would play a major role in the effects obtained. However, these hypotheses must be consolidated, in particular by detailing the initial role of cell death. Several questions remain, on the chronology of cell death in the different treated subpopulations, on the uptake by phagocytes, but especially on the type of cell death induced according to the cell type (necroptosis, apoptosis, pyroptosis, autophagy). The data generated will allow for validation or detail of the mechanisms of resolution of the inflammation and/or the anti-tumour effect observed.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: July 2023
• Est. primary completion date: July 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Adult patients

• Treated with ECP for at least 1 month, for control of GVHD in hematopoietic cell allograft (acute or chronic GVHD), treatment and control of cellular or humoral rejection in solid organ transplantation (heart, lung, kidney) or in the treatment of cutaneous T-cell lymphoma

Exclusion Criteria:

• Subjects with limited legal capacity.

• Subjects judged by the investigator to be unlikely to comply with study procedures

• Subjects with no social security coverage.

• Pregnant women.

• Subjects still in the exclusion period of another study, or according to the national registry of clinical trial participants.

Related Conditions & MeSH terms

• Cutaneous T-Cell Lymphoma
• Graft Rejection
• Graft Vs Host Disease
• Lymphoma, T-Cell, Cutaneous

Intervention

Other:
• Samples collection
Sampling of 2 samples on the extracorporeal photochemotherapy circuit, before and after sensitization with 8-MOP and UVA irradiation (without additional puncture)

Locations

Country	Name	City	State
France	Centre Hospitalier Universitaire de Besançon	Besançon

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Besancon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Type of cell death induced by 8-MOP sensitization and UVA irradiation	Caspase-3 activation in Western blot	24 hours
Primary	Type of cell death induced by 8-MOP sensitization and UVA irradiation	Gasdermin D cleavage in Western blot	24 hours
Primary	Type of cell death induced by 8-MOP sensitization and UVA irradiation	MLKL (mixed lineage kinase domain-like pseudokinase) phosphorylation in Western blot	24 hours