Infections

All Conditions

Symptoms and General Pathology

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Communicable Diseases

Epstein-Barr Virus Infections

Lymphoproliferative Disorders

Virus Diseases

Lymphatic Diseases

Immunoproliferative Disorders

Herpesviridae Infections

DNA Virus Infections

Tumor Virus Infections

Post-transplant Lymphoproliferative Disease

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Rituximab

Antineoplastic Agents, Immunological

Immunologic Factors

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.

Natalia Pinzon

Deepali Kumar, MD

Deepali Kumar

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.

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.

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.

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

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

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.

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

University Health Network, Toronto

Neoplasms

Lymphoma

Lymphosarcoma

Hematinics

Gastrointestinal Agents

Immunomodulating Agents

Liver Extracts

Pancrelipase

Pancreatin

Participants who have failed rituximab will receive IV tabelecleucel.

Participants who have failed both rituximab and chemotherapy will receive IV tabelecleucel.

Tabelecleucel is being investigated as an off-the-shelf, allogeneic T-cell immunotherapy for the treatment of EBV+ malignancies and diseases.

tabelecleucel

Aditi Mehta, DO

Amandeep Salhotra, MD

Huynh Cao, MD

Neena Kapoor, MD

Herbert Eradat, MD

William Asch, MD

Udeme Ekong, MD

Amer Beitinjaneh, MD, MPH, MSc

Suhag Parikh, MD

Jean Koff, MD

Sonali Chaudhury, MD

Satayaijt Kosuri, MD

Patrick Hagen, MD

Jean Yared, MD

Sarah Nikiforow, MD

Armin Ghobadi, MD

Koen Van Besien, MD

Ran Reshef, MD

Kevin Curran, MD

Michael Kent, MD

Matthew McKinney, MD

Hanna Rabi, MD

Robert Baiocchi, MD, PhD

Nemecek Eneida, MD

Nancy Bunin, MD

Michelle Hudspeth, MD

Bhagirathbhai Dholaria, MD

Luis Pineiro, MD

Tamra Slone, MD

Kris Michael Mahadeo, MD

James Butterworth, MD

Shyam Panicker, MD, MBBS, MRCP, FRACP, FRCPA

Daniel Chambers, MBBS, MRCP, FRACP, MD

Devendra Hiwase, MD

Rachel Conyers, MD, MBBS, FRACP

Duncan Purtill, MD, MBBS, FRACP, FRCPA

Nina Worel, MD

Willems Evelyne, MD

Daan Dierickx, MD

Victor Lewis, MD

Joerg Krueger, MD

Arjun Law, MD

Edouard Forcade, MD

Eolia Brissot, MD

Franck Morschhauser, MD

Benedicte Neven, MD

Sylvain Choquet, MD

Roberto Cairoli, MD

Patrizia Comoli, MD

Simona Sica, MD

Franco Locatelli, MD

Giaccone Luisa, MD

Eva González-Barca, MD

Lucrecia Yanez, MD

Pere Barba, MD

Gillen Oarbeascoa, MD

Jose Perez-Simon, MD

Juan Montoro, MD

Sridhar Chaganti, MD

Daniele Avenoso, MD

Eduardo Olavarria, MD

The purpose of this study is to determine the clinical benefit and characterize the safety profile of tabelecleucel for the treatment of Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV+ PTLD) in the setting of (1) solid organ transplant (SOT) after failure of rituximab and rituximab plus chemotherapy or (2) allogeneic hematopoietic cell transplant (HCT) after failure of rituximab.

This is a multicenter, open-label, phase 3 study to assess the efficacy and safety of tabelecleucel for the treatment of EBV+ PTLD in the setting of SOT after failure of rituximab and rituximab plus chemotherapy (SOT cohort) or HCT after failure of rituximab (HCT cohort).

Enrollment will be preceded by confirmation of availability of partially human leukocyte antigen (HLA) matched and restricted tabelecleucel for the participant.

Study procedures and product administration will be the same for each cohort. Tabelecleucel will be administered in cycles lasting 5 weeks (35 days). During each cycle, participants will receive intravenous tabelecleucel at a dose of 2×10\^6 cells/kg on Days 1, 8, and 15, followed by observation through Day 35. Treatment will continue until maximal response, unacceptable toxicity, initiation of non protocol therapy, or failure of tabelecleucel with up to 2 different HLA restrictions (SOT cohort) or up to 4 different HLA restrictions (HCT cohort). The study includes a total of 5 years of follow-up for disease and survival status.

This protocol has been amended to include the HCT cohort from clinical study ATA129-EBV-301 (NCT03392142).

NOTE, 29 April 2020: Enrollment is temporarily paused at study site/locations with status "active, not recruiting" due to COVID-19 restrictions.

Tabelecleucel for Solid Organ or Allogeneic Hematopoietic Cell Transplant Participants With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) After Failure of Rituximab or Rituximab and Chemotherapy

Multicenter, Open-Label, Phase 3 Study of Tabelecleucel for Solid Organ or Allogeneic Hematopoietic Cell Transplant Subjects With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease After Failure of Rituximab or Rituximab and Chemotherapy

Atara Biotherapeutics

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Acute Graft Versus Host Disease

Patients undergoing bronchoscopy for the diagnosis of a lesion with probe based laser endomicroscopy (pCLE) imaging before biopsy

Patients undergoing bronchoscopy for the detection of acute rejection of lung transplant with probe based laser endomicroscopy (pCLE) imaging before biopsy

pCLE will be added to standard bronchoscopy for the purpose of characterizing lung cancer or for characterizing of acute rejection in transplanted lungs.

probe based laser endomicroscopy (pCLE)

Cesar Keller, MD

Kyle Hogarth, MD

Doug Arenberg, MD

Adam Wellikoff, MD

Patients will be enrolled that are undergoing bronchoscopy for diagnosis of discrete lung lesions or for detection of acute rejection following lung transplants. The hypothesis is that bronchoscopy together with probe-based endomicroscopy (pCLE)results in improved and/or incremental diagnostic yield (definitive diagnosis) over conventional bronchoscopy.

The primary aim of this study is to develop the criteria to differentiate healthy versus diseased tissue in patient with discrete lung lesions or to characterize acute lung rejection in patients with transplanted lungs. Once these criteria have been defined, the diagnostic parameters and the reproducibility of pCLE will be assessed.

Registry Trial to Determine pCLE Image Interpretation Criteria and Preliminary Accuracy in the Lung

Registry Trial to Determine pCLE Image Interpretation Criteria and Preliminary Accuracy: Discrete Pulmonary Lesions and Acute Rejection in Transplanted Lungs

Mauna Kea Technologies

Thoracic Diseases

Thoracic Diseases (which includes but not limited to the following: thoracic neoplasms (masses/nodules) malignant or benign, interstitial lung diseases (ILD), chronic obstructive pulmonary disease (COPD), thoracic infections, thoracic malignancies metastatic to other organs, other cancers metastatic to the thoracic cavity.

Tissue Banking

Aaron Bungum

Karlyn Pierson, RN

Eric Edell, MD

The purpose of the registry will be to support ongoing research in the etiology, early diagnosis, clinical management, and prognosis of lung cancer and other cancers and diseases of the thorax by developing a complete repository of specimens from patients with thoracic disease including but not limited to suspected lung cancer, mediastinal and pleural tumors, lung transplants and from patients at a very high risk of developing other thoracic cancers or other thoracic diseases.

The primary objective of this proposal is to develop a Thoracic Specimen Registry at Mayo Clinic. The purpose of the registry will be to support ongoing research in the etiology, early diagnosis, clinical management, and prognosis of lung cancer and other cancers and diseases of the thorax by developing a complete repository of specimens from patients with thoracic disease including but not limited to suspected lung cancer, mediastinal and pleural tumors, lung transplants and from patients at a very high risk of developing other thoracic cancers or other thoracic diseases. Collected specimens will include peripheral blood, bronchoalveolar lavage (BAL) fluid, pleural fluid, tissue (surgical resections \& biopsies) and touch prep samples. The specimens will be stored in a central location at Mayo Clinic and managed by the Mayo Clinic Thoracic Specimen Registry Steering Committee. The registry will be a foundation for the development and implementation of research protocols and clinical trials that will enhance current knowledge of etiology and detection, discovery of new molecular and biochemical markers for screening, early diagnosis, and develop state-of-the-art therapeutic and preventive interventions for managing patients with, or at risk for, thoracic cancers or other thoracic diseases.

A blood sample will be collected at the time of consent/baseline. Optional subsequent blood draws maybe requested no more frequently than every 8 weeks. Patients scheduled for their clinically indicated thoracic procedure and have excess of clinical diagnostic tissue available will have tissue kept in the registry for future research. Patients scheduled for their clinical indicated bronchoscopy or CT guided procedure may have a sample go through the Touch Prep process and slides/cells will be kept for future research.

Patients scheduled for clinically indicated bronchoscopy with bronchoalveolar lavage BAL or Thoracentesis (TAP) procedure as part of that procedure may have fluid that is in excess of clinical diagnostic material, saved of future research. In addition, at the time of any future clinically indicated blood draws, thoracic procedures, thoracic resections, or metastatic thoracic primary tumors resections from other organs tissue will be requested for the research study.

Thoracic Specimen Registry

Mayo Clinic

Prinicpal

Sarcoma

Sarcoma, Kaposi

Castleman Disease

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Vascular Tissue

Soft Tissue Sarcoma

Kaposi Sarcoma

Unicentric Castleman Disease

Lung transplant candidates and recipients

Liver transplant candidates and recipients

Kidney transplant candidates and recipients

Diagnostic test for HHV8 exposure

Valeria Rossetti, MD

Letizia Corinna Morlacchi, MD

Solid organ transplant candidates will undergo serological screening for HHV8 at time of listing and transplantation.

In the event of a recipient/donor mismatch R-/D+ or in the presence of a seropositive recipient (R+), blood levels of HHV8 DNA will be monitored together with specific IGRA for HHV8.

Patients on the waiting list for solid organ transplantation will undergo serological screening for HHV8 (lytic and latent antigens) in the pre-transplant phase, both at time of listing and then at the time of transplantation; if seropositivity is found, further investigations will be performed, i.e. blood levels of HHV8 DNA and specific Elispot for HHV8.

As for donors, serological testing for HHV8 (lytic and latent antigens) will be performed.

AFTER SOLID ORGAN TRANSPLANTATION

* Patients found HHV8 seropositive in the pretransplant phase (R +), being at risk of HHV8 reactivation, will be monitored monthly in terms of viremia (HHV8 DNA) and specific IGRA for HHV8 for the first 6 months after transplantation and subsequently every 3 months up to 12 months post transplant.
* In case of patients who were found HHV8 seronegative at time of transplantation, donor serology will be evaluated. In case of R-/D+ mismatch, SOT recipients will receive the same monitoring of R + patients (blood levels of HHV8 DNA and specific IGRA for HHV8 monthly for the first 6 months and then every 3 months up to 12 months after transplantation).
* With reference to lung transplant patients, in cases of R + or R- / D +, HHV8 DNA will also be searched on the BAL obtained during surveillance bronchoscopies (usually at 3, 6 and 12 months after transplantation).

HHV8 and Solid Organ Transplantation

Screening for HHV8 Infection in Solid Organ Transplantation Donors, Candidates and Recipients

Incidence of HHV8 seropositivity among solid organ transplantations donors, candidates and recipients

Incidence of HHV8 mismatch between solid organ transplantations donors and recipients

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Ex-vivo Delivery of Rituximab to Prevent PTLD in EBV Mismatch Lung Transplant Recipients: A Pilot Trial	NCT04507477	Epstein-Barr Vi... Post-transplant...	Rituximab	18 Years -	University Health Network, Toronto
Tabelecleucel for Solid Organ or Allogeneic Hematopoietic Cell Transplant Participants With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) After Failure of Rituximab or Rituximab and Chemotherapy	NCT03394365	Epstein-Barr Vi... Solid Organ Tra... Lymphoprolifera... Allogeneic Hema... Stem Cell Trans...	tabelecleucel	-	Atara Biotherapeutics
Registry Trial to Determine pCLE Image Interpretation Criteria and Preliminary Accuracy in the Lung	NCT01793246	Lung Neoplasms Disorder Relate...	probe based las...	18 Years -	Mauna Kea Technologies
Thoracic Specimen Registry	NCT04118660	Thoracic Diseas... Lung Cancer Lung Transplant	Tissue Banking	18 Years -	Mayo Clinic
HHV8 and Solid Organ Transplantation	NCT05081141	HHV8 HHV8 Infection HHV8-Related Ma... Kaposi Sarcoma Lung Transplant... Liver Transplan... Kidney Transpla... Castleman Disea...	Diagnostic test...	18 Years -	Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Developing Optimal Parameters for Hyperpolarized Noble Gas and Inert Fluorinated Gas MRI of Lung Disorders	NCT02748798	Lung Transplant Lung Resection Lung Cancer Asthma Cystic Fibrosis Chronic Obstruc... Emphysema Mesothelioma Asbestosis Pulmonary Embol... Interstitial Lu... Pulmonary Fibro... Bronchiectasis Seasonal Allerg... Cold Virus Lung Infection Pulmonary Hyper... Pulmonary Dyspl... Obstructive Sle...	HP 3He HP 129Xe PFP SF6 129Xe Small and... 3He Human Lung ... PFP and SF6 Hum...	18 Years -	Thunder Bay Regional Health Research Institute
Tabelecleucel for Solid Organ or Allogeneic Hematopoietic Cell Transplant Participants With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) After Failure of Rituximab or Rituximab and Chemotherapy	NCT03394365	Epstein-Barr Vi... Solid Organ Tra... Lymphoprolifera... Allogeneic Hema... Stem Cell Trans...	tabelecleucel	-	Atara Biotherapeutics
DREAM: Double Lung Transplant REgistry Aimed for Lung-limited Malignancies	NCT05671887	Lung Cancer Bilateral Cance... Lung Transplant	Double Lung Tra...	18 Years - 75 Years	Northwestern University

Spots Global Cancer Trial Database for lung transplant