Extracorporeal Photopheresis in Lung Transplant Rejection for Cystic Fibrosis (CF) Patients

NCT03500575 | Unknown FDA Device

• 1 other identifier: 1708
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Background/Rationale Acute rejection (AR) is common in the first year after lung transplantation. AR has usually been reversible with treatment, but it can trigger chronic rejection that is the leading causes of late morbidity and mortality. Extracorporeal photopheresis (ECP) has emerged as a promising treatment for chronic rejection. The investigators postulate that the immunoregulatory property of ECP could promote graft tolerance immediately after lung transplantation. Objectives The aim of this trial is to evaluate the safety and efficacy of ECP as induction therapy for prevention of AR in recipients affected with cystic fibrosis in the first year after lung transplantation. The extracellular vesicles in the cell-to-cell communication and immunomodulation will be also investigated. Preliminary results (personal) A preliminary study, conducted in Vienna, demonstrated that 9 patients treated with ECP as induction therapy had 0% of chronic rejection versus 50% in the control group. The Institution hosting the current project is among largest lung transplantation centers in Italy with high rate of cystic fibrosis recipients. The Institution has experience in ECP and a dedicated instrument was specifically bought for the project. Internal collaborators have strong expertise in biological aspects including the extracellular vesicle compartment.

Conditions

Lung Transplant Rejection

Keywords

induction therapy, photopheresis

Outcome Measures

Primary Outcomes (1)

• Acute Rejection (measure: number of events)

  The diagnosis of acute rejection is done by transbronchial biopsy which are classified according the International Society of Heart and Lung Transplantation (ISHLT) grading. In alternative, the diagnosis of acute rejection is done by presence of one of the following clinical or radiological findings: reproducible decrease in lung function (FEV1), hypoxemia (pO2 \< 60mmHg, Sao2\< 90%), pulmonary infiltrates, pleural effusions or dyspnea without evidence of infection

  36 months

Secondary Outcomes (10)

• Infections from cytomegalovirus (CMV), bacteria, fungi, non-CMV virus, tuberculosis, parasitic (measure: number of events)

  12 months

• overall survival

  12 months

• cumulative immunosuppressive therapy (measure: mg)

  12 months after transplant

• total hospitalization days after discharge (measure: days)

  at 6 months and 12 months after primary discharge

• freedom from chronic lung allograft disease (measure: months)

  12 months

Study Arms (2)

photopheresis

EXPERIMENTAL

Device: photopheresis

control

NO INTERVENTION

Interventions

photopheresis DEVICE

• Treated group will receive ECP with Therakos online system. Each session consists in 1 treatment for 2 consecutive days. First session stars within 72 hours after transplantation followed by a session weekly for 3 time and 2 sessions for the next 2 months (6 sessions = 12 treatment)

photopheresis

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with CF undergoing first lung transplantation
• Male or female
• Any ethnicity
• Patients must have a body weight more than 40 kg
• Patients must have a platelet count more than 20.000/cmm
• Patients must be willing of understanding the purpose and risks of the study and must sign a statement of informed consent
• Patients transplanted in the first year from the study beginning.

You may not qualify if:

• Previous organ transplantation
• Women who are pregnant and/or lactating
• Patients with hypersensitivity or allergy to both heparin and citrate products
• Patients who are unable to tolerate extracorporeal volume shifts associated with ECP treatment due to the presence of any of the following conditions:uncompensated congestive heart failure, pulmonary edema, renal failure or hepatic failure
• Patients who are transplanted following the Italian criteria for emergency transplantation.
• Patients who stay more than 72 hours in ICU

Sponsors & Collaborators

• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: lead
• Italian Cystic Fibrosis Research Foundation: collaborator

Study Sites (1)

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Related Publications (4)

• Schwartz J, Winters JL, Padmanabhan A, Balogun RA, Delaney M, Linenberger ML, Szczepiorkowski ZM, Williams ME, Wu Y, Shaz BH. Guidelines on the use of therapeutic apheresis in clinical practice-evidence-based approach from the Writing Committee of the American Society for Apheresis: the sixth special issue. J Clin Apher. 2013 Jul;28(3):145-284. doi: 10.1002/jca.21276.

  PMID: 23868759 BACKGROUND

• Aubin F, Mousson C. Ultraviolet light-induced regulatory (suppressor) T cells: an approach for promoting induction of operational allograft tolerance? Transplantation. 2004 Jan 15;77(1 Suppl):S29-31. doi: 10.1097/01.TP.0000112969.24120.64.

  PMID: 14726767 RESULT

• Durazzo TS, Tigelaar RE, Filler R, Hayday A, Girardi M, Edelson RL. Induction of monocyte-to-dendritic cell maturation by extracorporeal photochemotherapy: initiation via direct platelet signaling. Transfus Apher Sci. 2014 Jun;50(3):370-8. doi: 10.1016/j.transci.2013.11.008. Epub 2013 Nov 28.

  PMID: 24360371 RESULT

• Righi I, Fenizia C, Trabattoni D, Nosotti M, Grisorio G, Vanetti C, di Tella S, Mocellin C, Fantini N, Prati D, Morlacchi LC, Rossetti V, Blasi F, Clerici M, Rosso LP. Extracorporeal photopheresis as induction therapy in lung transplantation for cystic fibrosis: a pilot randomized trial. Front Immunol. 2025 May 16;16:1583460. doi: 10.3389/fimmu.2025.1583460. eCollection 2025.

  PMID: 40453071 DERIVED

MeSH Terms

Interventions

Photopheresis

Intervention Hierarchy (Ancestors)

PUVA Therapy; Ultraviolet Therapy; Phototherapy; Therapeutics; Extracorporeal Circulation; Surgical Procedures, Operative

Central Study Contacts

mario nosotti, MD

CONTACT

+390255035570; mario.nosotti@unimi.it

ilaria righi

CONTACT

+390255038853; ilaria.righi@policlinico.mi.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Pilot study, single center, randomized controlled trial, single blind, 2 parallel arms

Study Record Dates

• First Submitted: March 2, 2018
• First Posted: April 18, 2018
• Study Start: May 20, 2018
• Primary Completion: December 10, 2021
• Study Completion: December 20, 2021
• Last Updated: May 11, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)