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

NCT04507477 | Unknown Phase 1 DMC

• 1 other identifier: 19-6260
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Epstein-Barr Virus Infections; Post-transplant Lymphoproliferative Disorder

Keywords

Rituximab; EBV; EVLP; lung transplant

Outcome Measures

Primary Outcomes (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.

  1 week post-transplant

Secondary Outcomes (1)

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

  12 months post-transplant

Study Arms (1)

Rituximab + Ex-vivo lung perfusion

EXPERIMENTAL

Donor 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.

Biological: Rituximab

Interventions

Rituximab BIOLOGICAL

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.

Also known as: Rituxan

Rituximab + Ex-vivo lung perfusion

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

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

Toronto, Ontario, M5G2N2, Canada

RECRUITING

MeSH Terms

Conditions

Epstein-Barr Virus Infections

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Deepali Kumar

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Natalia Pinzon

CONTACT

416-340-4241; natalia.pinzon@uhn.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 4, 2020
• First Posted: August 11, 2020
• Study Start: July 7, 2020
• Primary Completion: December 7, 2022
• Study Completion: February 7, 2023
• Last Updated: August 2, 2022

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)