AzTrials
AzTrials

Epstein-Barr Virus InfectionsPhase 1/2NCT04507477

Ex-vivo Delivery of Rituximab to Prevent PTLD in EBV Mismatch Lung Transplant Recipients: A Pilot Trial

A Phase 1/2 study testing Rituximab in people with Epstein-Barr Virus Infections and Post-transplant Lymphoproliferative Disorder, run by University Health Network, Toronto at 1 site in Canada.

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 The sponsor has not verified this record for over two years, so it may be out of date.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

Trial summary

Post-transplant lymphoproliferative disorders (PTLD) can present as a type of malignancy that limits patient and graft survival after solid organ transplantation. Many early PTLDs are driven by the Epstein-Barr Virus (EBV). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Rituximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteCanada
Study dates
7 Jul 2020to 7 Feb 2023
Phase
Phase 1/2
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age >=18 years
  • Listed for single or double lung transplantation
  • EBV (EBNA IgG and/or VCA IgG) seronegative (tested within the last 12 months)

Who cannot join

  • EBV seropositivity at any time prior to transplant
  • History of Cancer (eg, lymphoma)
  • History of receiving rituximab or allergy to rituximab
  • Underlying immunodeficiency (eg, common variable immune deficiency)
  • Unable or unwilling to comply with study procedures

Trial locations and contacts

1 site in 1 country.

Natalia Pinzon contact

416-340-4241

natalia.pinzon@uhn.ca

Canada1 site, 1 recruiting

  • University Health Network, Toronto General Hospital, Multi-Organ Transplant

    Toronto, Ontario, M5G2N2

    Deepali Kumar, MD, +1 416 340 4800 ext. 4241, deepali.kumar@uhn.ca

    Recruiting

Other trials in Canada

About this study

Official title: Ex-vivo Delivery of Rituximab to Prevent Post-transplant Lymphoproliferative Disease in Epstein-Barr Virus Mismatch Lung Transplant Recipients: A Pilot Trial

Post-transplant lymphoproliferative disorders (PTLD) can present as a type of malignancy that limits patient and graft survival after solid organ transplantation. Many early PTLDs are driven by the Epstein-Barr Virus (EBV).

Once acquired, EBV virus establishes latency in B-cells and can reactivate under immunosuppression. The highest risk transplant type to develop PTLD are lung transplants who have newly acquired EBV from their donors (D+/R-). There are no good modalities to prevent PTLD from developing after transplant. Rituximab is a monoclonal antibody that depletes B-cells thereby also reducing the burden of EBV. However, rituximab can have toxicities when given intravenously including infusion reactions and increased risk of reactions.

Furthermore, more than one dose is usually required. The Toronto Transplant program has developed a technology called ex vivo lung perfusion that repairs lungs outside of the body. Preliminary work has shown that rituximab given through the EVLP circuit can coat B-cells. We have also shown that there is no toxicity to the lung by giving rituximab. The current highly novel study proposes to treat donor lungs ex-vivo with rituximab in order to decrease the amount of B-cells and EBV in the graft. These lungs will then be transplanted into EBV negative patients with the hope that transmission of EBV would be reduced or prevented. Ten patients will be included in the current trial. Outcomes include safety, EBV viral load, and B-cell measurements in biopsies.

Read the detailed description

Previous studies have shown that EBV D+/R- lung transplant patients have a high rate of post-transplant lymphoproliferative disease up to 22%. Various methods have been proposed to decrease the risk of PTLD in EBV D+/R- organ transplants. These include a) antiviral prophylaxis with valganciclovir; b) EBV viral load monitoring and reduction of immunosuppression; c) avoidance of polyclonal antibody induction; d) treatment of EBV viremia with ganciclovir +/- intravenous immunoglobulin; e) pre-emptive systemic rituximab for EBV viremia. Antiviral strategies which include (val)ganciclovir in particular do not have proven efficacy in this setting. In addition, current antivirals do NOT target latent virus which would be the predominant form of virus in the allograft, and is also the predominant viral state that drives B-cell proliferation. Rituximab is a chimeric monoclonal antibody that targets CD20+ B-cells. It has been used clinically for many years to treat a variety of diseases and is used in transplantation for induction. Rituximab has been used successfully as a prophylactic and therapeutic drug for the reduction of EBV viremia and PTLD in hematopoietic stem cell transplant recipients. Ex-Vivo Lung Perfusion (EVLP) is a novel method of donor lung preservation and treatment developed in Toronto which allows donor lungs to be treated for up to 12h or more under protective physiological conditions. This essentially creates a critical time window in which donor lungs can be optimally repaired prior to transplant. An advantage of ex-vivo delivery of rituximab includes the ability to deliver high-doses locally to the graft while potentially avoiding serious adverse effects in the recipient. Pre-clinical studies have shown that adding rituximab to the perfusate allows for safe delivery of the drug directly to the lungs and adjacent lymph nodes and is non-toxic. EBV D+/R- lung transplant patients have a high rate of PTLD. There are no proven prevention measures. Rituximab is a commonly used medication in transplant patients as well as for other indications. Rituximab depletes B cells in lung tissues and may reduce the transmission of EBV, thereby preventing PTLD. Giving Rituximab directly to the lungs will avoid systemic toxicity in the patient. The investigators hypothesize that donor lungs treated with Rituximab during ex vivo lung perfusion will result in B-cell depletion and therefore be less likely to transmit EBV, thereby reducing the risk of PTLD in the lung recipient. As noted above the advantages of delivering rituximab ex vivo include prevention of adverse effects of rituximab including systemic depletion of B-cells, reduced systemic immunosuppression, and infusion-related toxicities, and ability to deliver a high-dose locally to the allograft.

Being tested
Rituximab
Keywords
Rituximab, EBV, EVLP, lung transplant
Medical subject headings
Epstein-Barr Virus Infections

What participants receive

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

  • RituximabBiological

    Also called Rituxan

    For EBV seropositive lungs meant for an EBV seronegative recipient, one dose of rituximab (500mg) will be added to the EVLP perfusate and be allowed to circulate for 3-4 hours.

Study groups in NCT04507477
Study groupRoleWhat they receive
Rituximab + Ex-vivo lung perfusionExperimentalDonor lungs deemed suitable for such patients will undergo ex vivo lung perfusion (EVLP) as per standard practice. In clinical practice almost all adult donor lungs are EBV seropositive. If in the rare case the donor lung is EBV seronegative, then the lung transplant candidate/recipient will no longer need to be part of the study. Therefore, for EBV seropositive lungs meant for an EBV seronegative recipient, one dose of rituximab (500mg) will be added to the EVLP perfusate and be allowed to circulate for 3-4 hours. Lungs will then be transplanted as per standard procedure.
Receives: Biological: Rituximab

What is being measured

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

  1. Number of patients with Primary Graft Dysfunction

    Primary graft dysfunction (PGD) will be measured using previously defined criteria: PGD2 will be a PaO2:FiO2 of 200-300 mmHg with pulmonary edema on chest radiograph whereas PGD3 will be a PaO2:FiO2 of <200 mmHg with pulmonary edema on chest radiograph or use of ECMO.

    Measured: 1 week post-transplant

Secondary outcomes (1)

  1. Number of patients with plasma EBV viral load of >=10,000 copies/mL

    Plasma EBV viral load of >=10,000 copies/mL. This will be compared to historic controls.

    Measured: 12 months post-transplant

Timeline

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

  1. First posted11 Aug 2020
  2. Study start7 Jul 2020
  3. Primary completion7 Dec 2022 (estimated)
  4. Study completion7 Feb 2023 (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 1/2
Primary purpose
Prevention
Allocation
Not applicable
Intervention model
Single group
Model description
At our institution, approximately 50% of donor lungs are put on ex-vivo lung perfusion (EVLP) for clinical purposes. If a patient consents to participate in this study and their donor is EBV positive, the donor lungs will first be put on EVLP. Rituximab will be administered to the donor lungs while they are on EVLP for 3 to 4 hours before the transplant is done in order to reduce the amount of EBV virus. The amount of time the donor lungs are on EVLP will not be changed as a result of participating in this study.
Masking
None (open label)
Enrolment
10 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04507477
Sponsor's protocol ID
19-6260
Status last verified
Jul 2021
First submitted
4 Aug 2020
Last updated
2 Aug 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Rituximab in people with Epstein-Barr Virus Infections and Post-transplant Lymphoproliferative Disorder, run by University Health Network, Toronto at 1 site in Canada.

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 3 inclusion and 5 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 2 Aug 2022. 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 Canada. 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.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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 Natalia Pinzon (416-340-4241, natalia.pinzon@uhn.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of patients with Primary Graft Dysfunction (time frame: 1 week post-transplant). 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 NCT04507477.

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 2 Aug 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in