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Lung Transplant RejectionPHORLUCYNCT03500575

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

A study testing photopheresis in people with Lung Transplant Rejection, run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico at 1 site in Italy.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Any age
Conditions the study is for
Lung Transplant Rejection
What is being tested?
photopheresis
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteItaly
Study dates
20 May 2018to 20 Dec 2021
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

Italy1 site
  • Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

    Milan, 20122

    Mario Nosotti, MD, +390255035570, mario.nosotti@unimi.it

    Ilaria Righi, MD, +390255038853 ext. righi, ilaria.righi@policlinico.mi.it

Other trials in Italy

About this study

Official title: Extracorporeal Photopheresis as Induction Therapy to Prevent Acute Rejection After Lung Transplantation in Cystic Fibrosis Patients

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.

Read the detailed description

The aim of this pilot trial is evaluate the efficacy and safety of ECP as induction therapy for prevention of AR in recipients affected of cystic fibrosis in the first year after lung transplantation.

The investigators postulate that ECP could induce graft immunotolerance avoiding the development of chronic rejection. Exposing T-cells to ultraviolet light results in DNA damage and apoptosis; such form of cell death does not typically stimulate a prolonged inflammatory cascade. When re-infused to the patient, apoptotic T-cells are surrounded by antigen presenting cells (APCs). The large number of APCs encircling the damaged T-cells limits the inflammatory response and stimulates specific signalling cascades in APCs that result in anti-inflammatory cytokine production; finally, immature dendritic cells could gain tolerogenic phenotypes. Based on this process, a theory postulates that the immuno-modulation secondary to ECP is related to a general increase in regulatory T-cells that cause a down-regulation of immune responses involved in chronic rejection onset. Another theory assumes that suppressor T-cells may acquire anti-clonal immunity prompted by the APCs; therefore, a sort of T-cell vaccination is the result of leukocyte apoptosis. The intention is to use this T-cell regulation to induce immunotolerance toward the graft before the development of chronic rejection, in spite to operate when the damage is in progress. To activate this effect from the first hours after transplantation, it can be useful the immunomodulatory activity of extracorporeal photopheresis, already established by clinical studies applied to the treatment of acute and chronic rejection.

The efficacy of ECP as induction therapy will be measured with the identification of AR rate in the study group versus the control group. AR is diagnosed with trans-bronchial biopsy and graded using standard histological criteria: A0 (none), A1 (minimal), A2 (mild), A3 (moderate) or A4 (severe). A stable 10% decrease of forced expiratory volume in 1 second (FEV1) on baseline will be considered as AR even though trans-bronchial biopsy is not available. In addition, lymphocyte immunophenotype (with particular regard to CD4 + and CD25 +), the cytokine profile (interleukine (IL) 4, IL-10, IL-12 measured by High Resolution Cytokines Array) and the extracellular vesicles content are tested to assess the therapeutic response. Finally, anti-HLA antibodies are tested to understand their dynamics.

The ECP safety is assessed by recording every adverse effect with specific attention to opportunistic infections.

In conclusion, this study aims to verify whether the induction therapy with ECP can dramatically decrease the rate of acute rejection in order to impact positively on the main cause of mortality in lung transplantation: the chronic rejection.

Being tested
photopheresis
Keywords
induction therapy, photopheresis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • photopheresisDevice

    • 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)
Study groups in NCT03500575
Study groupRoleWhat they receive
photopheresisExperimentalNot described
Receives: Device: photopheresis
controlNo interventionNot described

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 36 months

Secondary outcomes (10)
  1. Infections from cytomegalovirus (CMV), bacteria, fungi, non-CMV virus, tuberculosis, parasitic (measure: number of events)

    Bronchoscopy with microbiologic, bacteriology, mycology, virology, parasitology and tuberculosis investigation will be performed

    Measured: 12 months

  2. overall survival

    The overall survival will be registered in the first year after lung transplant. It will be reported as months to death and the cause of death

    Measured: 12 months

  3. cumulative immunosuppressive therapy (measure: mg)

    cumulative doses of Tacrolimus, azathioprine (AZT) and corticosteroids at 12 months

    Measured: 12 months after transplant

  4. total hospitalization days after discharge (measure: days)

    The average number of days spent in the hospital during the first year after transplant

    Measured: at 6 months and 12 months after primary discharge

  5. freedom from chronic lung allograft disease (measure: months)

    The efficacy of ECP as induction therapy will be measured with the identification of AR rate in the study group versus the control group. AR is diagnosed with trans-bronchial biopsy and graded using standard histological criteria: A0 (none), A1 (minimal), A2 (mild), A3 (moderate) or A4 (severe). A stable 10% decrease of forced expiratory volume in 1 second (FEV1) on baseline will be considered as AR even though trans-bronchial biopsy is not available

    Measured: 12 months

  6. side effects of ECP (measure: number of events)

    The ECP safety is assessed by recording every adverse effect with specific attention to opportunistic infections

    Measured: 3 months after the latest treatment with ECP

  7. lymphocyte immunophenotype (measure: pg/ml) by cluster of differentiation (CD)

    lymphocyte immunophenotype (CD45, CD3, CD19, CD14, CD56/16, CD4, CD8, HLA-DR (human leukocyte antigen D Related), CD16, CD25, CD127, CD11c, Annexin/PI)

    Measured: At time zero and 48 hours after the end of each sessions of two ECP treatments peripheral blood samples will be collected

  8. cytokine profile of interleukyn (IL) (number/mmc; percentage)

    the cytokine profile (IL-4, IL-10, IL-12 measured by High Resolution Cytokines Array) are tested to assess the therapeutic response.

    Measured: At time zero and 48 hours after the end of each sessions of two ECP treatments peripheral blood samples will be collected

  9. extracellular vesicles content (measure: number/ml)

    extracellular vesicles are important mediators of intercellular communication, being involved in the transmission of biological signals between cells. Number, membrane antigens, mRNA (messenger of ribonucleic acid) and protein content are tested. We use nanoparticle tracking analysis for the testing

    Measured: At time zero and 48 hours after the end of each sessions of two ECP treatments peripheral blood samples will be collected

  10. anti-HLA antibodies profile (measure: µmg/ml)

    the anti-HLA antibodies will be tested by Luminex methodology

    Measured: At time zero, after 7 days of the end of each cycle of treatment, at 3, 6 months and one year after transplantation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Apr 2018
  2. Study start20 May 2018 (estimated)
  3. Primary completion10 Dec 2021 (estimated)
  4. Study completion20 Dec 2021 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Model description
Pilot study, single center, randomized controlled trial, single blind, 2 parallel arms
Masking
Double blind
Who is masked
Investigator, Outcomes assessor
Enrolment
24 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03500575
Sponsor's protocol ID
1708
Acronym
PHORLUCY
Status last verified
May 2018
First submitted
2 Mar 2018
Last updated
11 May 2018
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 23868759
  • 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.

    PubMed 14726767
  • 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.

    PubMed 24360371
  • 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.

    PubMed 40453071

Questions about this trial

What is this clinical trial studying?

A study testing photopheresis in people with Lung Transplant Rejection, run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 11 May 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact mario nosotti, MD (+390255035570, mario.nosotti@unimi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Acute Rejection (measure: number of events) (time frame: 36 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03500575, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2018.

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