Infections

All Conditions

Symptoms and General Pathology

Rare Diseases

Recurrence

Communicable Diseases

Cytomegalovirus Infections

Disease Attributes

Herpesviridae Infections

Virus Diseases

DNA Virus Infections

Cytomegalic Inclusion Disease

Anti-Infective Agents

Antirheumatic Agents

Dermatologic Agents

All Drugs and Chemicals

Antineoplastic Agents

Cyclosporine

Cyclosporins

Letermovir

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Antiviral Agents

Participants will be hematopoietic cell transplantation (HCT) recipients with a history of CMV infection. INTERVENTIONAL COHORT: Patients receive letermovir PO QD (or IV over 1 hour for patients unable to receive PO) for 14 weeks in the absence of disease progression or unacceptable toxicity.

OBSERVATIONAL COHORT: Patients undergo collection of blood samples for CMV-CMI analysis via CMV immunity T cell panel assay on day 100. Patients with negative CMI on day 100 undergo collection of blood samples for retesting on day 180.

Patients enrolled on the study will receive oral LTV 480 mg daily (240 mg daily for patients receiving cyclosporine A). The maximum duration of LTV administration will be 14 weeks. Patients receiving oral medication will be administered a pill diary for drug compliance purposes. This will be administered and reconciled in clinic.

Letermovir Pill

Collection of blood samples for CMV-CMI analysis via CMV immunity T cell panel assay on day 100. Patients with negative CMI on day 100 undergo collection of blood samples for retesting on day 180.

blood draw

Genovefa Papanicolaou, MD

Yeon Joo Lee, MD

Jo-Anne Young, MD

Genovefa Papanicolaou

The purpose of this study is to determine of letermovir (LTC) is effective at preventing Cytomegalovirus (CMV) infection from returning in people who have already had CMV infection after a bone marrow transplant.

A Study of the Drug Letermovir (LTV) as Prevention for Recurrent of Cytomegalovirus (CMV) Infection

An Open-label, Single-arm Study of Letermovir (LTV) for Prevention of Recurrent CMV Infection in High-risk Hematopoietic Cell Transplant (HCT) Recipients

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Merck Sharp & Dohme LLC

Memorial Sloan Kettering Cancer Center

Neoplasms

Blood and Lymph Conditions

Hematologic Neoplasms

Hematologic Diseases

Immunomodulating Agents

The first 3 patients will receive a single infusion of bulk CMV-TCR transduced donor-derived T cells on first CMV reactivation post allogeneic HSCT, at a dose of 10\^4 T cells/kg recipient weight

If no cases grade III-IV GVHD in Cohort 1 the remaining patients (N=7) each receive a single infusion of bulk CMV-TCR transduced donor-derived T cells on first CMV reactivation post allogeneic HSCT, at a dose of 10\^5 T cells/kg recipient weight

If 1 case grade III-IV GVHD in Cohort 1, next three patients to be treated with a single infusion of bulk CMV-TCR transduced donor-derived T cells of 1 x 10\^3 T cells/kg recipient weight

CMV-TCR transduced donor-derived T cells

Emma Morris, Prof

Hans Stauss, Prof

The study will test the hypothesis that CMV TCR-transduced T cells, at a specific T-cell dose/kg, can generate a functional CMV immune response post-transplant, where CMV-specific donor T cells cannot be isolated by conventional means. This will be tested in the context of adult HLA-matched sibling allogeneic HSCT.

In the proposed trial, an HLA-A\*0201-restricted CMV pp65-specific T cell receptor (TCR) will be introduced into donor T cells via ex vivo GMP retroviral transduction. Donor T cells will be isolated from peripheral blood following a simple venesection procedure. The CMV TCR-transduced T cells will be tested for TCR expression, CMV-specific cytokine secretion and microbiological contamination before being frozen and stored at -80C. CMV seropositive transplant recipients will be tested weekly for CMV reactivation by quantitative PCR on peripheral blood. On first detection of CMV DNA \> 200 copies/ml, 104 (cohort 1) or 105 (cohort 2) bulk CMV TCR-transduced T cells/kg recipient weight will be infused into the patient.

Blood will be taken regularly to determine persistence and expansion of the CMV TCR-transduced T cells. Weekly CMV PCR will be continued. Patients will be examined at appropriate intervals (daily if inpatients, twice weekly in BMT clinic if outpatients) for the development of graft versus host disease (GVHD) or other potential side effects.

Reactivation of the latent human herpes virus, Cytomegalovirus (CMV), post allogeneic haematopoietic stem cell transplantation (Allo-HSCT) can result in significant morbidity and mortality unless treated promptly. Anti-viral therapy is usually effective, but has serious side effects typically requiring prolonged inpatient admission, such as myelosuppression (Ganciclovir) or nephrotoxicity (Foscarnet). Cellular immunotherapy for CMV has been tested in Phase I/II trials in the UK and Europe. In these trials CMV-specific T cells were isolated from the peripheral blood of CMV seropositive donors and re-infused into recipients following CMV reactivation resulting in sustained anti-viral responses. It is clear that post-transplant recovery of CD8+ CMV-specific cytotoxic T-cells (CTL) abrogates the development of CMV-related disease. An advantage of cellular therapy for CMV reactivation is the transfer of immunological memory, which can reduce the number of subsequent reactivations. This is important, as rapidly increasing numbers of highly immunosuppressive (or T cell depleted) reduced intensity conditioning Allo-HSCTs are being performed in the UK. These approaches reduce the toxicity of transplantation in older patients with more co-morbidities. Reduced intensity allogeneic transplants are currently part of the UK MRC AML15 trial and are to be recommended in the proposed MRC/ECOG UKALL14 study and again in UK MRC AML17. In addition, a number of NCRN approved UK multicentre extended Phase II studies have recently started using reduced intensity Allo-HSCT in various lymphoma subtypes.

Transplant recipients with CMV seronegative donors cannot benefit from currently available cellular immunotherapy approaches due to the lack of CMV-specific memory T cells in these donors. At present, there is no reliable strategy to isolate virus specific T cells from uninfected naïve individuals, as the precursor frequency is low or absent and the in vitro priming of T-cell responses is inefficient. T-cell receptor (TCR) gene transfer offers a strategy to produce antigen-specific T cells independent of precursor frequency and without the need for T-cell priming. As approximately 50% of adult individuals have been previously infected with CMV, there are significant numbers of CMV 'mismatched' Allo-HSCT performed, where the donor is CMV seronegative and the recipient CMV seropositive. The proposed study will test the feasibility of generating donor-derived CMV-specific T cells via the ex vivo introduction of a CMV-specific T cell receptor using a GMP grade retroviral vector.

Study of Adoptive Immunotherapy With Donor-derived CMV-specific T Cells for Recipients of Allo-HSCT

CMV TCR Gene Therapy: A Phase I Safety, Toxicity and Feasibility Study of Adoptive Immunotherapy With CMV TCR-transduced Donor-derived T Cells for Recipients of Allogeneic Haematopoietic Stem Cell Transplantation

CMV-TCR transduced cells express vbeta13 and murine constant beta chain (mCb), both of which can be easily detected by flow cytometry. The frequency of vbeta13+/mCb+ is used to calculate the efficiency of transduction of donor-derived cells.

Flow cytometry and TCR repertoire analysis can be used to evaluate overall T-cell subset reconstitution.

Quantitative real-time PCR using primers specifically targeting nucleotide sequences that are only present in the introduced CMV-TCR can be used to determine the number of circulating CMV-TCR transduced cells post infusion.

Flow cytometry can be used to further characterise CMV-TCR transduced cells in terms of naive/memory subsets (based on the expression of CD45RO and CD62L differentiation markers), proliferation status (assessed by Ki-67) and ability to produce cytokines (such as IFN-gamma and TNF-alpha).

University College, London

Epstein-Barr Virus Infections

Adenoviridae Infections

Tumor Virus Infections

Altretamine

Allogeneic CD4+ and CD8+ T lymphocytes ex vivo incubated with synthetic peptides of the viral antigens of Cytomegalovirus, Adenovirus and Epstein-Barr Virus

Max dose:

* HLA-matched (8/8) donors: 1.0 x 10e5 T cells/kg recipient BW
* HLA-mismatched donors: 2.5 x 10e4 T cells/kg recipient BW

Min. dose:

- 10 T cells/kg recipient BW

Suspension of multivirus-specific T cells in 20 mL of 0.9% NaCl + 0.5% HSA

Cell therapy product which is individually produced for each patient and administered via IV bolus injection.

Multivirus (CMV, EBV, AdV)-specific T cells

Tobias Feuchtinger, Prof

Theresa Käuferle, Dr

Philippe Lewalle, Prof

Ann De Becker, Dr.

Tessa Kerre, Prof

Johan Maertens, Prof. Dr.

Johan Maertens, Prof.

Yves Beguin, Prof.

Bénédicte Bruno, Dr.

Marie Ouachée-Chardin, Dr.

Daniele Bensoussan, Prof.

Maud D'Aveni-Piney, Dr.

Stéphanie Nguyen Quoc, Prof.

Bendedicte Neven, Prof.

Jean Hugues Dalle, Prof.

Johannes Schulte, Prof.

Martin Bornhäuser, Prof.

Roland Meisel, Prof.

Stefan Schönberger, Dr.

Brigitte Strahm, PD Dr.

Britta Maecker-Kolhoff, Prof.

Vladan Vucinic, Dr.

Tobias Feuchtinger, Prof.

Irene Teichert von Lüttichau, PD Dr.

Johanna Tischer, Dr.

Mareike Verbeek, Dr.

Jürgen Föll, Prof.

Peter Lang, Prof.

Hermann Einsele, Prof.

Matthias Wölfl, Prof.

Franco Locatelli, Prof.

Franca Fagioli, Prof.

Peter van Balen, Dr.

Pere Barba, Dr.

María Laura Fox, Dr.

Antonio Pérez-Martinez, Dr.

José Antonio Pérez Simón, Dr.

Juan Montoro Gómez, Dr.

Haematopoietic stem cell transplantation (HSCT) can expose patients to a transient but marked immunosuppression, during which viral infections are an important cause of morbidity and mortality. Adoptive transfer of virus-specific T cells is an attractive approach to restore protective T-cell immunity in patients with refractory viral infections after allogeneic HSCT. The aim of this Phase III trial is to confirm efficacy of this treatment in children and adults.

For a growing number of patients suffering from various conditions as, e.g., haematological malignancies or diverse genetic disorders, haematopoietic stem cell transplantation (HSCT) or bone marrow transplantation offer the only possible curative options. However, HSCT is associated with three major risks: graft rejection, graft-versus-host disease (GvHD) and opportunistic, mostly viral, infections or reactivations resulting from delayed immune reconstitution. Delayed immune reconstitution, however, often is the direct result of the severe pre-transplantation conditioning treatment and T-cell depletion of the transplant necessary to fight the risks of graft rejection and GvHD. Therefore, the risk for life-threatening opportunistic, mostly viral, infections is increased in post-transplantation patients. The most common infections after HSCT are Cytomegalovirus (CMV), Epstein-Barr virus (EBV) and Adenovirus (AdV).

The standard treatment approach for viral infections/reactivations is chemotherapy which shows limited efficacy and does not restore immunity. Therefore, effective new treatment options are required for this condition.

Previous investigations have shown that sufficient T-cell immunity is essential for the control and prevention of viral reactivations and newly occurring infections after HSCT. The infusion of T-cells is therefore a promising new approach to treat immune-comprised patients. However, infusion with unselected T cells is associated with an increased risk for GvHD due to the high content of alloreactive T cells. A very promising approach to minimize this problem is to remove alloreactive T cells and enrich, isolate and purify virus-specific T cells.

This approach has been studied for nearly two decades and the data published up to date indicate that virus-specific T-cell responses after adoptive T-cell transfer protect against virus-related complications post HSCT and restore T-cell immunity, in particular for AdV-, CMV- and EBV-infections. Despite these promising results, virus-specific T-cell transfer is not yet translated into daily clinical practice due to the lack of prospective clinical trials confirming the efficacy of this treatment approach.

The overall goal of this Phase III, double-blind placebo-controlled study is to test efficacy of multivirus-specific T cells to bring this treatment method in clinical routine. Multivirus-specific T cells generated in this study will be directed against all three most common post-HSCT viral infections: AdV, CMV and EBV. Thus, T-cell immunity will be restored to fight and prevent new viral infections.

After an initial screening visit, patients eligible to participate in the study will be treated within 28 days after screening. Patients will be randomized in a 2:1 (treatment: placebo) ratio and receive a single infusion with either multivirus-specific T cells or placebo. Patients will be followed up on the day of treatment, 1 day after and 1, 2, 4, 8 and 15 weeks after treatment. Treatment success will be measured by assessing different parameters including symptoms, quality of life, viral load and T-cell immunity in blood samples.

Patients eligible to participate in this study are adult and paediatric patients who have received allogeneic stem cell transplantation and suffer from new or reactivated EBV, AdV or CMV infection refractory to standard antiviral treatment for two weeks. Patients from the six European countries Germany, Belgium, Netherlands, UK, France and Italy will be enrolled. In total 130 patients plus 19 screening failures are expected to participate in the study.

Randomization will be stratified with respect to three age groups: Children up to 6 years, children \>6 and up to 18 years, and adults \>18 years. Accordingly, for each stratum, a separate randomization list will be provided. Randomization will be performed by a representative of the Simbec-Orion Group who will be independent in the sense that he / she will otherwise not be involved in the TRACE trial.

Multivirus-specific T-cell Transfer Post SCT vs AdV, CMV and EBV Infections

Treatment of Chemo-refractory Viral Infections After Allogeneic Stem Cell Transplantation With Multispecific T Cells Against CMV, EBV and AdV: A Phase III, Prospective, Multicentre Clinical Trial

Percentage of patients with viral clearance (defined as two consecutive negative PCRs) to determine efficacy of multispecific T-cell transfer in patients with chemo-refractory viral infections after allogeneic stem cell transplantation

Percentage of patients with progression between Day 7 and Week 8 after T-cell Transfer to determine efficacy of multispecific T-cell transfer in patients with chemo-refractory viral infections after allogeneic stem cell transplantation

Incidence of newly occurring acute GvHD grade I from Day 0 to Week 8 and Week 15.

Incidence of chronic GvHD from Day 7 to Week 8 and to Week 15 after treatment.

Time to newly occurring acute and chronic GvHD.

Severity of acute GvHD ≥ grade II until Week 8 and Week 15.

Acute maximum toxicity on the day of T-cell transfer evaluated by measuring vital signs prior to and at different times after the T-cell transfer from 1 hour prior to T-cell transfer to 4 hours post infusion.

Change in viral load of underlying viral infection as assessed by quantitative PCR analysis of peripheral blood; samples taken weekly from Day 7 to Week 8 after IMP transfer as compared to samples taken at Day 0.

Percentage of patients with ≥1 log decrease in CMV, EBV or AdV viral load at Week 8.

Number of reactivations of the underlying viral infection following initial viral clearance until end of follow-up.

Number of patients with reduction or clearance of clinical symptoms of underlyingviral infection from Day 7 to Week 8 after IMP transfer as compared to Day 0.

Overall survival rate (OS): From Day 0 to end of follow-up.

Number of days requiring antiviral chemotherapy after T-cell transfer from Day 7 to Week 8 after T-cell transfer.

Time to last administration of defined antiviral medication or switch to prophylactic treatment from Day 0 to Week 8 after IMP transfer.

Number of new viral reactivations (CMV, AdV or EBV) other than the underlying viral infection per patient as assessed by PCR analysis and clinical symptoms throughout the study to evaluate the putative prophylactic effect of the treatment.

Number of days hospitalized after IMP transfer from Day 7 to Week 8.

EQ-5D for adult patients (≥18 years) at Screening and Week 8 to evaluate life quality in adults. A scale from 0 to 100 is used with 100 being best value and 0 the worst.

FACT-BMT for adult patients (≥18 years) at Screening and Week 8 to evaluate life quality in adults.

The patients have to answer questions about their physicial, social, emotional and functional wellbeing. A scale from 0 to 4 is used with 0= not at all, 1= a little bit, 2=somewhat, 3=quite a bit, 4=very much.

PEDS-QL for paediatric patients (\<18 years) at Screening and Week 8 to evaluate life quality in children.

The patients and /or their parents have to answer questions about pain and hurt, fatigue and sleep, nausea, worry, Nutrition, thinking and communication.

A scale from 0 to 4 is used with 0=never a Problem, 1=almost never a problem, 2= sometimes a problem, 3=often a problem, 4= almost always a problem.

T-cell phenotyping, samples taken at Screening, Day 0 and each visit from Day 7 to Week 15 after treatment.

Analysis of virus-specific T cells: frequencies of in vivo expanded virus-specific T cells in peripheral blood samples taken at Screening, Day 0, Day 7 to Week 15 after treatment.

Assessment of the cellular composition, in particular the percentage of IFN-gamma+ cells, in the IMP.

Drop-out rate at Day 0 and reasons for drop-out.

Number of days from Screening to Day 0 (day of IMP transfer) to evaluate the required time frame.

Documentation of incidence, severity and type of adverse events from Day 0 to Week 8 and serious adverse events throughout the study to evaluate safety.

Physical examinations will be conducted to identify possible clinically significant pathologies. These findings will be recorded at each visit. The Karnofsky/Lansky index will be included in the physical examination at Screening and at Week 8 only.

supine systolic and diastolic blood preasure in mm Hg

haemoglobin, leukocytes, thrombocytes, dirfferential blood count (neutrophil granulocytes, lymphocytes, monocytes and easinophil granulocytes), total and conjugated Bilirubin, C reactive Protein (CRP), creatinine, Alanin aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl Transferase (GGT), Lactate Dehydrase (LDH), Urea.

A list of normal ranges will be provided from each site.

All concomitant medication will be recorded from Screening until Week 8. The generic name, indication, route of administration, dose/ unit, start and stop date or ongoing, way of application will be documented.

During follow-up Week 15, only antiviral therapy, immunosuppression and SAE-related concomitant medication as well as chemotherapy will be documented.

The generic name, indication, route of administration, dose/ unit, start and stop date or ongoing, way of application will be documented.

Cellular treatment also has to be documented as concomitant medication.

European Commission

Simbec-Orion Group Ltd, Merthyr Tydfil, UK

Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany

Leiden University Medical Center, LUMC, Leiden, The Netherlands

Centre Hospitalier Universitaire de Nancy, CHU, Vandoeuvre-Lès-Nancy, France

Ghent University Hospital, UZG, Ghent, Belgium

Ospedale Pediatrico Bambino Gesù, OPBG, Rome, Italy

Newcastle University, UNEW, Newcastle, UK

Vall d'Hebron Institute of Oncology (VHIO) and Banc de Sang I Teixits (BST), Barcelona, Spain

Prof. Tobias Feuchtinger

Prof. Dr. med Tobias Feuchtinger

Phase I (dose escalation) : An open, single-arm, dose-escalation clinical study to explore the safety, tolerability, and cytodynamic characteristics of CMV and EBV-specific T cells (VSTs), with initial efficacy observations. Subjects enrolled with refractory CMV and/or EBV infection after allogeneic hematopoietic stem cell transplantation were subjected to a 3+3 dose-climb test. Exploring the safety, dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of intravenous infusion of multi-virus VSTs.

(2) Phase II (dose expansion) : According to the clinically recommended or safe and effective dose determined by the phase I climb test, the extended study of 1-2 dose groups with 20 cases per dose was performed after joint review by the investigators and project collaborators.

Subjects will receive partial HLA-matched viral-specific T cells (VSTs) against both CMV and EBV on one of the following dose levels:

Level One: 1 x 10\^7 cells/m2 Level Two: 2 x 10\^7cells/m2 Level Three: 5x 10\^7 cellss/m2

Virus specific T cells

Yuanjie Ding

Xuying Pei

Xiangyu Zhao

To evaluate the safety and tolerability of partial HLA-matched VSTs against both CMV and EBV viruses in recipients of allogeneic hematopoietic stem cells with refractory viral infections (CMV and/or EBV).

Preliminary evaluation of the efficacy of partial HLA-matched VSTs against both CMV and EBV viruses in recipients of allogeneic hematopoietic stem cells with refractory viral infections (CMV and/or EBV); To monitor the duration and expansion of multi-virus VSTs cells after infusion.

This study consists of two parts: (1) The first stage is the safety evaluation of multi-virus VSTs and the exploration of DLT and MTD; (2) The second phase is to evaluate the safety and efficacy of multi-viral VSTs in selecting appropriate doses in the first phase.

Multivirus-specific T Cells in the Treatment of Refractory CMV and/or EBV Infection After Allo-HSCT

An Exploratory Clinical Study of Multivirus-specific T Cells in the Treatment of Refractory Cytomegalovirus and/or Epstein-Barr Virus Infection After Allogeneic Hematopoietic Stem Cell Transplantation

Number of participants with treatment-related adverse events as assessed by CTCAE v5.0, and graft-versus-host-disease will be summarized using descriptive statistics for each dose level

Antiviral efficacy including clinical signs of viral infections, virus reinfection, and laboratory measurement of viral load after VSTs infusion will be determined

Laboratory measurement of virus-specific immune reconstitution before and after VSTs infusion will be tested

Peking University People's Hospital

Professor

Patients will receive up to 2 x 10\^7 CHM-CTL/m2 as a single infusion and may receive up to 4 additional infusions at intervals of at least 2 weeks.

Trivirus-Specific CTLs

Helen E Heslop, MD

Subjects have a type of blood cell cancer, other blood disease or a genetic disease for which they received a stem cell transplant. After transplant while the immune system grows back the subjects have an infection with one or more of three viruses - Epstein Barr virus (EBV), cytomegalovirus (CMV) or adenovirus - that has persisted or come back despite standard therapy.

Adenovirus is a virus that causes symptoms of a common cold normally but can cause serious life-threatening infections in patients who have weak immune systems. It usually affects the lungs and can cause a very serious pneumonia, but it can also affect the gut, the liver, the pancreas and the eyes.

CMV is a virus that can also cause serious infections in patients with suppressed immune systems. It usually affects the lungs and can cause a very serious pneumonia, but it can also affect the intestinal tract, the liver and the eyes. Approximately 2/3 of normal people harbor this virus in their body. In healthy people CMV rarely causes any problems because the immune system can keep it under control. If the subject and/or the subject's donor are positive for CMV, s/he is at risk of developing CMV disease while his/her immune system is weak post transplant.

EBV is the virus that causes glandular fever or kissing disease. It is also normally controlled by a healthy immune system, but when the immune system is weak, it can cause fevers, enlarged lymph nodes and sometimes develop into a type of cancer called lymphoma.

This treatment with specially trained T cells (called CTLs) has had activity against these viruses when the cells are made from the transplant donor. However, as it takes 2-3 months to make the cells, that approach is not practical when the subject already has an infection. We want to find out if we can use CTLs which have already been made from another donor that match the subject and his/her donor as closely as possible and if the CTLs will last in the body and have activity against these viruses.

In a recent study these cells were given to 50 patients with viral infections post transplant and over 70% had a complete or partial response. The purpose of this study is to make CTL lines leftover from that previous study available to patients with viral infections that have not responded to standard treatments.

These virus-specific CTLs are an investigational product not approved by the FDA.

The CTL lines were made at Baylor College of Medicine from donors for other transplant patients or other normal donors from the National Marrow Donor Program. All donors were screened in the same way as blood donors. When the CTL lines were made, blood was taken from the donors and used to grow T cells. To do this, we first infected a type of blood cells called monocytes with a specially produced adenovirus gene that also carries part of the CMV gene. The monocytes with these new genes then stimulated the T cells. This stimulation trained the T cells to kill cells with this part of the CMV virus or with adenovirus.

We then grew these CTLs with more stimulation with EBV infected cells (which we made from donor blood by infecting them with EBV in the laboratory). We also put the adenovirus that carries the CMV gene into these EBV infected cells so that they too had CMV and adenovirus proteins. These EBV infected cells were treated with radiation so they cannot grow. By this type of culture, we grew out T cells that can see and attack cells infected with EBV, adenovirus or CMV. Once we made sufficient numbers of T cells we tested them to make sure they killed cells infected with these viruses and then froze them.

The cells will be thawed and injected into an intravenous line over 1-5 minutes.

All participants on this study will get the same dose of cells. However if the subject's infection responds to the CTLs, s/he may be offered up to 4 more doses at two-week intervals. If the infection does not respond, the doctors may also try a line from a different donor.

Allogeneic Virus-Specific Cytotoxic T-Lymphocytes(CTL), Persistent/Recurrent Viral Infection Post-HSCT (EAP CHALLAH)

Expanded Access Protocol: Most Closely HLA Matched Allogeneic Virus Specific Cytotoxic T-Lymphocytes (CTL) to Treat Persistent Reactivation or Infection With Adenovirus, CMV and EBV After HSCT

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of the Drug Letermovir (LTV) as Prevention for Recurrent of Cytomegalovirus (CMV) Infection	NCT04017962	CMV CMV Infection Hematopoietic C...	Letermovir Pill blood draw	12 Years -	Memorial Sloan Kettering Cancer Center
Study of Adoptive Immunotherapy With Donor-derived CMV-specific T Cells for Recipients of Allo-HSCT	NCT02988258	Haematological ... CMV Infection	CMV-TCR transdu...	18 Years - 65 Years	University College, London
Multivirus-specific T-cell Transfer Post SCT vs AdV, CMV and EBV Infections	NCT04832607	AdV Infection EBV Infection CMV Infection Stem Cell Trans...	Multivirus (CMV...	2 Months -	LMU Klinikum
A Study of the Drug Letermovir (LTV) as Prevention for Recurrent of Cytomegalovirus (CMV) Infection	NCT04017962	CMV CMV Infection Hematopoietic C...	Letermovir Pill blood draw	12 Years -	Memorial Sloan Kettering Cancer Center
Multivirus-specific T Cells in the Treatment of Refractory CMV and/or EBV Infection After Allo-HSCT	NCT06075927	CMV Infection EBV Infection Stem Cell Trans...	Virus specific ...	18 Years - 70 Years	Peking University People's Hospital
Study of Adoptive Immunotherapy With Donor-derived CMV-specific T Cells for Recipients of Allo-HSCT	NCT02988258	Haematological ... CMV Infection	CMV-TCR transdu...	18 Years - 65 Years	University College, London
Allogeneic Virus-Specific Cytotoxic T-Lymphocytes(CTL), Persistent/Recurrent Viral Infection Post-HSCT (EAP CHALLAH)	NCT01945619	EBV Infection CMV Infection Adenoviral Infe...	Trivirus-Specif...	-	Baylor College of Medicine

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