Ex-vivo Delivery of Rituximab to Prevent PTLD in EBV Mismatch Lung Transplant Recipients: A Pilot Trial
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04507477|
Recruitment Status : Recruiting
First Posted : August 11, 2020
Last Update Posted : August 11, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Epstein-Barr Virus Infections Post-transplant Lymphoproliferative Disorder||Biological: Rituximab||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Intervention 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)|
|Official Title:||Ex-vivo Delivery of Rituximab to Prevent Post-transplant Lymphoproliferative Disease in Epstein-Barr Virus Mismatch Lung Transplant Recipients: A Pilot Trial|
|Actual Study Start Date :||July 7, 2020|
|Estimated Primary Completion Date :||July 7, 2021|
|Estimated Study Completion Date :||July 7, 2021|
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.
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.
Other Name: Rituxan
- Number of patients with Primary Graft Dysfunction [ Time Frame: 1 week post-transplant ]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.
- Number of patients with plasma EBV viral load of >=10,000 copies/mL [ Time Frame: 12 months post-transplant ]Plasma EBV viral load of >=10,000 copies/mL. This will be compared to historic controls.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04507477
|Contact: Natalia Pinzonemail@example.com|
|University Health Network, Toronto General Hospital, Multi-Organ Transplant||Recruiting|
|Toronto, Ontario, Canada, M5G2N2|
|Contact: Deepali Kumar, MD +1 416 340 4800 ext 4241 firstname.lastname@example.org|
|Principal Investigator:||Deepali Kumar||University Health Network, Toronto|