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

Sponsor
University Health Network, Toronto
Study ID
NCT04507477
Phase
PHASE1/PHASE2
Status
Unknown

Conditions

  • Epstein-Barr Virus Infections
  • Post-transplant Lymphoproliferative Disorder

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

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.

Study Details

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.

Key Dates

Start date
Jul 7, 2020
Status verified
Jul 2021
Primary completion
Dec 7, 2022
Completion
Feb 7, 2023

Study Design

Enrollment
10 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION

Arms

  • Experimental: Rituximab + Ex-vivo lung perfusion
    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.

Primary Outcome Measure

Number of patients with Primary Graft Dysfunction [ Time Frame: 1 week post-transplant ]

Central Contacts

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