EBV ViremiaEarly Phase 1NCT07873970

25BT056: Basket Study of Viral Cytotoxic T Lymphocytes

A Early Phase 1 study testing Virus-Specific Cytotoxic T Lymphocytes (vCTLs) in people with EBV Viremia and CMV Viremia, run by Children's Hospital of Philadelphia.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts

Official record

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Trial summary

This study is evaluating the safety and effectiveness of virus-specific cytotoxic T lymphocytes (vCTLs) for treating difficult-to-control viral infections caused by cytomegalovirus (CMV), adenovirus (ADV), Epstein-Barr virus (EBV), or BK virus in children, adolescents, and young adults with weakened immune systems. Read more about this study

Who is it for?: Ages 0 to 29 years
Conditions the study is for: EBV Viremia, CMV Viremia, BK Viremia
What is being tested?: Virus-Specific Cytotoxic T Lymphocytes (vCTLs)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 35 participants
Where: No sites listed yet
Study dates: 1 Nov 2026to Nov 2037
Phase: Early Phase 1

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 0 to 29 years
All sexes
No healthy volunteers
Child, Adult

Recipient Inclusion Criteria

Subjects with inherited (e.g. SCID) or acquired immunodeficiency with evidence of refractory viral infection with one or more of CMV, adenovirus, EBV, or BK virus. Specifically:
Increasing viremia by quantitative PCR with increase from baseline over 7 days, or persistent detection after 14 days despite appropriate standard of care therapy (e.g. anti-viral therapy, withdrawal of immunosuppression), AND/OR
Progressive symptomatic viral infection evidenced by persistent clinical symptoms or end-organ disease attributable to the viral infection that has not improved after at least 7 days of appropriate standard-of-care therapy, or develops new clinical manifestations despite standard-of-care therapy, AND/OR
Antiviral resistance, or inability to receive appropriate antiviral therapy due to intolerance, toxicity, contraindication, or lack of a feasible antiviral treatment option.
Age 0 - 29 years at time of consent
Female subjects of reproductive potential, defined per Oncology clinical guidelines as all females ≥ 12 years old, or <12 years old who have reached menarche, must have a negative urine or serum pregnancy test. Testing may be performed using serum human chorionic gonadotropin (HCG) or urine
Subjects with reproductive potential must agree to use an effective method of birth control

Recipient Exclusion Criteria

Subjects with ≥ Grade 2 acute GVHD or moderate to severe chronic GVHD at the time of vCTL infusion
Subjects receiving systemic steroids (> 0.5mg/kg/day prednisolone equivalent) at the time of vCTL infusion
Receipt of donor lymphocyte infusion within the 4 weeks preceding vCTL infusion
Receipt of thymoglobulin, alemtuzumab, or other T cell immunosuppressive monoclonal antibody within the 4 weeks preceding vCTL infusion
End-organ involvement of virus in sites that may, in the opinion of the investigator, put the subject at risk of unacceptable toxicity e.g. retinitis, cerebritis, encephalitis
Known HIV infection
Any medical condition which could compromise participation in the study, in the opinion of the investigator
Female subjects who are pregnant or breastfeeding

Donor Inclusion Criteria

Age ≥ 18 years old
HLA match with the recipient of at least 3/6. Donor may be the original transplant donor or a third party donor
Consent to pre screening with PepTivator testing of T cell response to the relevant virus(es)
Willing to undergo formal donor evaluation equivalent to that required for hematopoietic stem cell transplant (HSCT) donors
Willing to consent to T cell processing under CHOP protocol CHP784 (IRB 04 004078) using the CliniMACS device

Donor Exclusion Criteria

Donors younger than 18 years old
HLA match with the recipient less than 3/6
Refusal or inability to consent to PepTivator pre screening
Unwillingness or inability to undergo formal donor evaluation (as required for HSCT donors)
Refusal or inability to consent to T cell processing under The Children's Hospital of Philadelphia protocol (CHP784, IRB 04 004078) using the CliniMACS device
Any medical, infectious, or other condition identified during evaluation that contraindicates donation per standard HSCT donor eligibility guidelines (e.g., active uncontrolled infection, significant cardiopulmonary disease, pregnancy) or that would preclude safe apheresis/T cell collection as determined by the evaluating clinicians.

Trial locations and contacts

No sites are listed yet. Contact the study team or a site near you to ask about taking part.

Megan Atkinson contact

215-590-2820

cttsbmtintake@chop.edu

Kellie Patterson, BSN, RN contact

215-590-2820

pattersok3@chop.edu

About this study

Official title: 25BT056: Basket Study of Viral Cytotoxic T Lymphocytes in Children, Adolescents and Young Adults With Viral Infection Following Allogeneic Hematopoietic Stem Cell Transplant, Solid Organ Transplant or in Primary Immunodeficiencies

vCTLs are immune cells collected from a related donor and selected to recognize and fight specific viruses. The cells are manufactured using the CliniMACS® Cytokine Capture System and administered by intravenous infusion. Additional infusions may be given if viral infection persists.

The study will assess the safety of vCTL therapy, including the risk of graft-versus-host disease (GVHD) and infusion-related reactions, as well as its ability to reduce viral infection, improve clinical outcomes, and support survival. Participants will be monitored for approximately 12 weeks after their final vCTL infusion. Participants will all receive vCTLs; there is no comparison group.

Participants will:

Have donor-derived vCTLs manufactured for infusion using the CliniMACS Cytokine Capture System
Receive the vCTLs through an intravenous infusion
Be monitored for side effects and infusion reactions, viral levels through blood testing, clinical outcomes, including response to treatment, survival, and time without detectable virus

Read the detailed description

Viral infection and reactivation are major causes of morbidity and mortality in individuals with inherited or acquired immunodeficiency, including recipients of allogeneic hematopoietic stem cell transplant and solid organ transplant. Cytomegalovirus, adenovirus, Epstein-Barr virus, and BK virus may cause severe, persistent, or progressive disease. Standard antiviral therapies may be ineffective, poorly tolerated, contraindicated, or limited by viral resistance.

This is a single-institution, open-label, prospective pilot basket study of donor-derived virus-specific cytotoxic T lymphocytes for treatment of refractory CMV, adenovirus, EBV, and/or BK virus infection. The vCTL product is manufactured from an adult related donor with at least a 3/6 human leukocyte antigen (HLA) match to the recipient. Following leukapheresis, donor cells are stimulated with virus-specific peptide pools and enriched for interferon-gamma-secreting T cells using the CliniMACS Cytokine Capture System on the CliniMACS Prodigy platform.

Participants will receive vCTLs by slow intravenous push. Dose is based on donor-recipient HLA matching. Additional infusions of the same dose may be administered every 2 weeks for persistent detectable viral replication, up to a maximum of five infusions, provided safety and redosing criteria are met.

Safety will be evaluated in aggregate across all viral cohorts, with particular focus on Grade 3 or higher acute graft-versus-host disease and Grade 3 or higher infusion-related reactions considered at least possibly related to vCTL infusion. Antiviral efficacy will be evaluated separately by virus type using quantitative polymerase chain reaction and clinical response assessments. Participants will be followed through 12 weeks after their final vCTL infusion.

Conditions: EBV Viremia, CMV Viremia, BK Viremia, Adenovirus, Post-transplant Lymphoproliferative Disorder, Viremia
Being tested: Virus-Specific Cytotoxic T Lymphocytes (vCTLs)
Keywords: Cytotoxic T Lymphocytes, vCTL, Virus-Specific T Cells, vCTL Therapy, Cellular Immunotherapy, Adoptive T-Cell Therapy, Antiviral Immunotherapy, Pediatric Transplant, Viral Reactivation, Resistant Viral Infection, CliniMACS Cytokine Capture System
Medical subject headings: Adenoviridae Infections, Viremia, Epstein-Barr Virus Infections, Virus Diseases, Primary Immunodeficiency Diseases, Severe Combined Immunodeficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Virus-Specific Cytotoxic T Lymphocytes (vCTLs)Biological
Also called vCTLs, Virus-specific T cells, Cytotoxic T lymphocyte therapy, Gamma-Capture Virus-Specific Cytotoxic T Lymphocytes
Donor-derived virus-specific cytotoxic T lymphocytes (vCTLs) targeting one or more of cytomegalovirus (CMV), adenovirus (ADV), Epstein-Barr virus (EBV), and BK virus. Cells are manufactured using the CliniMACS® Prodigy and CliniMACS Cytokine Capture System (IFN-γ) following stimulation with virus-specific PepTivator® peptide pools. vCTLs are administered by IV infusion at a dose of 2-3 × 10^4 CD3+ cells/kg recipient weight for HLA-matched related donors or 0.4-0.6 × 10^4 CD3+ cells/kg recipient weight for HLA-mismatched related donors. Additional infusions of the same dose may be administered every 2 weeks in subjects with ongoing clinically significant viral infection who continue to meet infusion eligibility criteria, for up to 5 total infusions. The intervention is intended for treatment of refractory viral infections in patients with inherited or acquired immunodeficiencies, including recipients of hematopoietic stem cell transplant.

Study groups in NCT07873970
Study group	Role	What they receive
Virus-Specific Cytotoxic T Lymphocytes (vCTLs)	Experimental	Participants with refractory CMV, ADV, EBV, and/or BK virus will receive donor-derived virus-specific cytotoxic T lymphocytes. Participants may receive a multivirus-specific product when clinically indicated. The initial infusion is administered on Day 0. Repeat infusions may be administered every 2 weeks, up to five total infusions, for ongoing detectable viral replication if eligibility criteria are met. Receives: Biological: Virus-Specific Cytotoxic T Lymphocytes (vCTLs)

What is being measured

The primary outcome is the main question the study is designed to answer.

Occurrence of Grade 3 or higher acute graft-versus-host disease (GVHD)
This outcome measures the number of participants who develop Grade 3 or higher acute graft-versus-host disease that is assessed as possibly, probably, or definitely related to vCTL infusion. Acute GVHD will be graded using the Center for International Blood and Marrow Transplant Research (CIBMTR) criteria.
Measured: From first vCTL infusion (Day 0) through 12 weeks after the final vCTL infusion
Occurrence of Grade 3 or higher infusion-related reactions
This outcome measures the number of participants who experience a Grade 3 or higher infusion-related reaction that is assessed as possibly, probably, or definitely related to vCTL infusion. Infusion-related reactions will be graded using NCI CTCAE version 6.0.
Measured: From first vCTL infusion (Day 0) through 12 weeks after the final vCTL infusion

Secondary outcomes (12)

Cytomegalovirus (CMV) Overall Response Rate
This outcome measures the number of participants who achieve a virologic or clinical response following completion of vCTL therapy. Response categories include complete Response (undetectable viral load), partial Response (≥1-log reduction in viral load), mixed response (virologic or clinical improvement without both), stable disease (changes insufficient to qualify as a complete response, partial response or progression), and progressive disease (increase in viral load by quantitative polymerase chain reaction (qPCR) of at least 1-log from baseline). Viral load will be assessed by qPCR, and clinical symptoms will be evaluated by the study team.
Measured: Two weeks after the final vCTL infusion
Adenovirus (ADV) Overall Response Rate
This outcome measures the number of participants who achieve a virologic or clinical response following completion of vCTL therapy. Response categories include complete Response (undetectable viral load), partial Response (≥1-log reduction in viral load), mixed response (virologic or clinical improvement without both), stable disease (changes insufficient to qualify as a complete response, partial response or progression), and progressive disease (increase in viral load by quantitative polymerase chain reaction (qPCR) of at least 1-log from baseline). Viral load will be assessed by qPCR, and clinical symptoms will be evaluated by the study team.
Measured: Two weeks after the final vCTL infusion
Epstein Barr Virus (EBV) Overall Response Rate
This outcome measures the number of participants who achieve a virologic or clinical response following completion of vCTL therapy. Response categories include complete Response (undetectable viral load), partial Response (≥1-log reduction in viral load), mixed response (virologic or clinical improvement without both), stable disease (changes insufficient to qualify as a complete response, partial response or progression), and progressive disease (increase in viral load by quantitative polymerase chain reaction (qPCR) of at least 1-log from baseline). Viral load will be assessed by qPCR, and clinical symptoms will be evaluated by the study team.
Measured: Two weeks after the final vCTL infusion
BK polyomavirus (BKV) Overall Response Rate
This outcome measures the number of participants who achieve a virologic or clinical response following completion of vCTL therapy. Response categories include complete Response (undetectable viral load), partial Response (≥1-log reduction in viral load), mixed response (virologic or clinical improvement without both), stable disease (changes insufficient to qualify as a complete response, partial response or progression), and progressive disease (increase in viral load by quantitative polymerase chain reaction (qPCR) of at least 1-log from baseline). Viral load will be assessed by qPCR, and clinical symptoms will be evaluated by the study team.
Measured: Two weeks after the final vCTL infusion
Cytomegalovirus (CMV) Overall Survival
This outcome measures the length of time participants remain alive after receiving CMV vCTL therapy.
Measured: From first vCTL infusion (Day 0) through 12 weeks after the final vCTL infusion
Adenovirus (ADV) Overall Survival
This outcome measures the length of time participants remain alive after receiving ADV vCTL therapy.
Measured: From first vCTL infusion (Day 0) through 12 weeks after the final vCTL infusion
Epstein Barr Virus (EBV) Overall Survival
This outcome measures the length of time participants remain alive after receiving EBV vCTL therapy.
Measured: From first vCTL infusion (Day 0) through 12 weeks after the final vCTL infusion
BK polyomavirus (BKV) Overall Survival
This outcome measures the length of time participants remain alive after receiving BK vCTL therapy. Overall survival will be evaluated separately for participants treated for CMV, adenovirus, EBV, and BK virus infections.
Measured: From first vCTL infusion (Day 0) through 12 weeks after the final vCTL infusion
Cytomegalovirus (CMV) Virus Free Survival
This outcome measures the length of time participants remain alive and without detectable viral infection following vCTL therapy. Viral clearance will be assessed using quantitative PCR.
Measured: From first vCTL infusion (Day 0) through 12 weeks after the final vCTL infusion
Adenovirus (ADV) Virus Free Survival
This outcome measures the length of time participants remain alive and without detectable viral infection following vCTL therapy. Viral clearance will be assessed using quantitative PCR.
Measured: From first vCTL infusion (Day 0) through 12 weeks after the final vCTL infusion
Epstein Barr Virus (EBV) Virus Free Survival
This outcome measures the length of time participants remain alive and without detectable viral infection following vCTL therapy. Viral clearance will be assessed using quantitative PCR.
Measured: From first vCTL infusion (Day 0) through 12 weeks after the final vCTL infusion
BK polyomavirus (BKV) Virus Free Survival
This outcome measures the length of time participants remain alive and without detectable viral infection following vCTL therapy. Viral clearance will be assessed using quantitative PCR.
Measured: From first vCTL infusion (Day 0) through 12 weeks after the final vCTL infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Nov 2026Nov 2037

First posted14 Oct 2026
Study start1 Nov 2026 (estimated)
Primary completionNov 2036 (estimated)
Study completionNov 2037 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (66)Papers the sponsor has linked to this study.
Other trials for EBV ViremiaStudies of the same condition, open and under way.
More trials run by Children's Hospital of PhiladelphiaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Early Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 35 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07873970
Sponsor's protocol ID: 25-023926
Status last verified: Oct 2026
First submitted: 5 Oct 2026
Last updated: 22 Oct 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Mahadeo KM, Baiocchi R, Beitinjaneh A, Chaganti S, Choquet S, Dierickx D, Dinavahi R, Duan X, Gamelin L, Ghobadi A, Guzman-Becerra N, Joshi M, Mehta A, Navarro WH, Nikiforow S, O'Reilly RJ, Reshef R, Ruiz F, Spindler T, Prockop S. Tabelecleucel for allogeneic haematopoietic stem-cell or solid organ transplant recipients with Epstein-Barr virus-positive post-transplant lymphoproliferative disease after failure of rituximab or rituximab and chemotherapy (ALLELE): a phase 3, multicentre, open-label trial. Lancet Oncol. 2024 Mar;25(3):376-387. doi: 10.1016/S1470-2045(23)00649-6. Epub 2024 Jan 31.
PubMed 38309282
Nikiforow S, Whangbo JS, Reshef R, Tsai DE, Bunin N, Abu-Arja R, Mahadeo KM, Weng WK, Van Besien K, Loeb D, Nasta SD, Nemecek ER, Zhao W, Sun Y, Galderisi F, Wahlstrom J, Mehta A, Gamelin L, Dinavahi R, Prockop S. Tabelecleucel for EBV+ PTLD after allogeneic HCT or SOT in a multicenter expanded access protocol. Blood Adv. 2024 Jun 25;8(12):3001-3012. doi: 10.1182/bloodadvances.2023011626.
PubMed 38625984
Hill JA, Mayer BT, Xie H, Leisenring WM, Huang ML, Stevens-Ayers T, Milano F, Delaney C, Sorror ML, Sandmaier BM, Nichols G, Zerr DM, Jerome KR, Schiffer JT, Boeckh M. The cumulative burden of double-stranded DNA virus detection after allogeneic HCT is associated with increased mortality. Blood. 2017 Apr 20;129(16):2316-2325. doi: 10.1182/blood-2016-10-748426. Epub 2017 Feb 16.
PubMed 28209721
Lindsay J, Kerridge I, Wilcox L, Tran S, O'Brien TA, Greenwood M, Chen SC, Kong DCM, Pergam SA, Liu C, Slavin MA. Infection-Related Mortality in Adults and Children Undergoing Allogeneic Hematopoietic Cell Transplantation: An Australian Registry Report. Transplant Cell Ther. 2021 Sep;27(9):798.e1-798.e10. doi: 10.1016/j.jtct.2021.05.028. Epub 2021 Jun 7.
PubMed 34111574
Kaeuferle T, Krauss R, Blaeschke F, Willier S, Feuchtinger T. Strategies of adoptive T -cell transfer to treat refractory viral infections post allogeneic stem cell transplantation. J Hematol Oncol. 2019 Feb 6;12(1):13. doi: 10.1186/s13045-019-0701-1.
PubMed 30728058
Lilleri D, Fornara C, Chiesa A, Caldera D, Alessandrino EP, Gerna G. Human cytomegalovirus-specific CD4+ and CD8+ T-cell reconstitution in adult allogeneic hematopoietic stem cell transplant recipients and immune control of viral infection. Haematologica. 2008 Feb;93(2):248-56. doi: 10.3324/haematol.11912.
PubMed 18245650
Annels NE, Kalpoe JS, Bredius RG, Claas EC, Kroes AC, Hislop AD, van Baarle D, Egeler RM, van Tol MJ, Lankester AC. Management of Epstein-Barr virus (EBV) reactivation after allogeneic stem cell transplantation by simultaneous analysis of EBV DNA load and EBV-specific T cell reconstitution. Clin Infect Dis. 2006 Jun 15;42(12):1743-8. doi: 10.1086/503838. Epub 2006 May 4.
PubMed 16705581
Barron MA, Gao D, Springer KL, Patterson JA, Brunvand MW, McSweeney PA, Zeng C, Baron AE, Weinberg A. Relationship of reconstituted adaptive and innate cytomegalovirus (CMV)-specific immune responses with CMV viremia in hematopoietic stem cell transplant recipients. Clin Infect Dis. 2009 Dec 15;49(12):1777-83. doi: 10.1086/648423.
PubMed 19911937
Heemskerk B, Lankester AC, van Vreeswijk T, Beersma MF, Claas EC, Veltrop-Duits LA, Kroes AC, Vossen JM, Schilham MW, van Tol MJ. Immune reconstitution and clearance of human adenovirus viremia in pediatric stem-cell recipients. J Infect Dis. 2005 Feb 15;191(4):520-30. doi: 10.1086/427513. Epub 2005 Jan 7.
PubMed 15655775
Jakharia N, Howard D, Riedel DJ. CMV Infection in Hematopoietic Stem Cell Transplantation: Prevention and Treatment Strategies. Curr Treat Options Infect Dis. 2021;13(3):123-140. doi: 10.1007/s40506-021-00253-w. Epub 2021 Jul 21.
PubMed 34305463
Shmueli E, Or R, Shapira MY, Resnick IB, Caplan O, Bdolah-Abram T, Wolf DG. High rate of cytomegalovirus drug resistance among patients receiving preemptive antiviral treatment after haploidentical stem cell transplantation. J Infect Dis. 2014 Feb 15;209(4):557-61. doi: 10.1093/infdis/jit475. Epub 2013 Aug 27.
PubMed 23983215
Boeckh M, Leisenring W, Riddell SR, Bowden RA, Huang ML, Myerson D, Stevens-Ayers T, Flowers ME, Cunningham T, Corey L. Late cytomegalovirus disease and mortality in recipients of allogeneic hematopoietic stem cell transplants: importance of viral load and T-cell immunity. Blood. 2003 Jan 15;101(2):407-14. doi: 10.1182/blood-2002-03-0993. Epub 2002 Sep 12.
PubMed 12393659
Sedlacek P, Petterson T, Robin M, Sivaprakasam P, Vainorius E, Brundage T, Chandak A, Mozaffari E, Nichols G, Voigt S. Incidence of Adenovirus Infection in Hematopoietic Stem Cell Transplantation Recipients: Findings from the AdVance Study. Biol Blood Marrow Transplant. 2019 Apr;25(4):810-818. doi: 10.1016/j.bbmt.2018.12.753. Epub 2018 Dec 20.
PubMed 30578939
Ison MG. Adenovirus infections in transplant recipients. Clin Infect Dis. 2006 Aug 1;43(3):331-9. doi: 10.1086/505498. Epub 2006 Jun 19.
PubMed 16804849
Lindemans CA, Leen AM, Boelens JJ. How I treat adenovirus in hematopoietic stem cell transplant recipients. Blood. 2010 Dec 16;116(25):5476-85. doi: 10.1182/blood-2010-04-259291. Epub 2010 Sep 13.
PubMed 20837781