MORPHEE : Mechanisms of Cell Death Induced by Extracorporeal Photochemotherapy (MORPHEE)

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.

Study Overview

• Status: Recruiting
• Conditions: Cutaneous T-Cell Lymphoma; Graft Rejection; Graft Vs Host Disease
• Intervention / Treatment: Other: Samples collection

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Charline VAUCHY, PhD; Phone Number: +33381218875; Email: cvauchy@chu-besancon.fr

Study Locations

• France
  • Besançon, France, 25000
    • Recruiting
    • CENTRE HOSPITALIER UNIVERSITAIRE de BESANCON
    • Principal Investigator: Thomas CREPIN, MD
    • Contact: Charline Vauchy, PhD; Email: cvauchy@chu-besancon.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Patients undergoing extracorporeal photochemotherapy	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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Type of cell death induced by 8-MOP sensitization and UVA irradiation	Caspase-3 activation in Western blot	24 hours
Type of cell death induced by 8-MOP sensitization and UVA irradiation	Gasdermin D cleavage in Western blot	24 hours
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

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Besancon

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2022
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: April 4, 2022
• First Submitted That Met QC Criteria: April 11, 2022
• First Posted (Actual): April 19, 2022

Study Record Updates

• Last Update Posted (Estimated): November 21, 2024
• Last Update Submitted That Met QC Criteria: November 19, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Cell death; Extracorporeal Photochemotherapy
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Graft vs Host Disease; Lymphoma, T-Cell, Cutaneous
• Other Study ID Numbers: 2022/679

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No