Viral Infections After HSCTPhase 1NCT02510417
Allogeneic Virus-specific T Cell Lines (VSTs)
A Phase 1 study testing VSTs in people with Viral Infections After HSCT, run by Catherine Bollard at 1 site in United States.
Trial summary
The primary purpose of the study is to evaluate whether most closely HLA-matched multivirus-specific T cell lines obtained from a bank of allogeneic virus-specific T cell lines (VSTs) have antiviral activity against three viruses: EBV, CMV and adenovirus. Read more about this study
- Who is it for?
- Ages 4 weeks to 45 years
- Conditions the study is for
- Viral Infections After HSCT
- What is being tested?
- VSTs
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Oct 2014to 3 Jan 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 4 weeks to 45 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Received prior myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplant using either bone marrow, single/double cord blood or PBSC
- Cells administered as;
- Treatment of persistent or relapsed reactivation or infection
- Early treatment for single or multiple infections with EBV, CMV and/or adenovirus
- Steroids less or equal to 0.5 mg/kg/day prednisone
- 5)Bilirubin <3x, AST <3x, Serum creatinine <2x upper limit of normal, Hgb >8.0, plts >20 6) Pulse oximetry of > 90% on room air 7) Available VSTs 8) Negative pregnancy test (if female of childbearing potential after reduced intensity conditioning) 9) Patient or parent/guardian capable of providing informed consent.
Who cannot join
- Received ATG, Campath or other T cell immunosuppressive monoclonal antibodies in the last 28 days.
- Patients with other uncontrolled infections
- Received donor lymphocyte infusion in last 28 days
- Evidence of GVHD > or equal to grade 2
- Active and uncontrolled relapse of malignancy
Trial locations and contacts
1 site in 1 country.
United States1 site
Childrens National Medical Center
Washington D.C., District of Columbia, 20010
About this study
Official title: Administration of Most Closely HLA-matched Multivirus-specific Cytotoxic T-Lymphocytes for the Treatment of EBV, CMV, Adenovirus Infections Post Allogeneic Stem Cell Transplant
The primary purpose of the study is to evaluate whether most closely HLA-matched multivirus-specific T cell lines obtained from a bank of allogeneic virus-specific T cell lines (VSTs) have antiviral activity against three viruses: EBV, CMV and adenovirus.
Reconstitution of anti-viral immunity by donor-derived VSTs has shown promise in preventing and treating infections associated with CMV, EBV and adenovirus post-transplant. However, the time taken to prepare patient-specific products and lack of virus-specific memory T cells in cord blood and seronegative donors, limits their value.
Read more
An alternative is to use banked partially HLA-matched allogeneic VSTs. A prior phase II study at our institution using trivirus-specific VSTs generated using monocytes and EBV-transformed B cells gene-modified with a clinical grade adenoviral vector expressing CMV-pp65 to activate and expand specific T cells showed the feasibility, safety and activity of this approach for the treatment of refractory CMV, EBV and Adenovirus infections. However, the production process was lengthy, requiring 8-12 weeks, with exposure to biohazards (B95.8 EBV viral strain and adenovector), while antigenic competition between different viral components precluded increasing the spectrum of specificity beyond these three viruses.
Investigator have overcome these limitations and in the current trial, they will evaluate whether rapidly generated, allogeneic most closely HLA-matched multivirus-specific VSTs, activated using overlapping peptide libraries spanning immunogenic antigens from CMV, adenovirus and EBV will be safe and produce anti-viral effects in allogeneic HSCT recipients infected with one of more of the targeted viruses that are persistent despite conventional anti-viral therapy. The study agent will be assessed for safety (stopping rules defined) and antiviral activity.
Read the detailed description
Investigators evaluated the clinical utility of Multivirus VSTs in recipients of matched related, matched unrelated, or haploidentical donor transplants. To date, 10 clinical-grade multivirus-directed VSTs have been generated from donor PBMCs. These lines were polyclonal, comprising both CD4+ (57±5%) and CD8+ (35±5%) cells and retained expression of the memory markers CD45RO+CD62L+ (58±8%). Their specificity was dependent on the prior viral exposure of the cell donor; 7/8 tested lines had activity against Adv,8/8 against CMV, 6/8 against EBV. None of the lines reacted against recipient PHA blasts - indicating lack of alloreactive potential in these rapidly generated lines.
Investigators administered these multivirus-specific donor-derived VSTs to 3 allogeneic HSCT recipients in a dose escalation study all on DL1 (5x106/m2). There were no immediate infusion toxicities, and no de novo acute GvHD, demonstrating the in vivo safety of these mVST. Further, antiviral efficacy has been observed in 1 patient with refractory CMV. In addition, in a recently published paper from Baylor College of Medicien (Anapoulous et al, STM 2014) they have treated VSTs manufactured with a similar methodology, but targeting 5 viruses instead of 3 with specificity to BK virus and HHV6. In that study 10 patients were treated with 4 on DL1 (5x10e6/m2), 4 on DL2 (1x10e7/m2) and 2 on DL3 (2x10e7/m2) and again saw no immediate infusion toxicities, and no de novo acute GvHD, demonstrating the in vivo safety of these mVST. Three patients received the cells as viral prophylaxis (days 38-43 post-HSCT) and none developed viral infections at up to 3 months post-treatment. The other 7 patients received the cells as treatment for one or more active infections between days 59-139 post-HSCT. Based on viral load measurements by day 42 post-infusion, the VSTs were successful in controlling active infections with CMV (1 complete (CR) and 1 partial response (PR)), EBV (2 CRs, including a case of frank PTLD); Adv (1 CR); HHV6 (1 CR); and BK (3 CR, 1 PR, 1NR). Of note, 3 BK virus responders had tissue disease with severe hemorrhagic cystitis and all had marked improvement or disappearance of hematuria following infusion. One patient subsequently had an episode of transient but severe bladder pain in association with inflammation seen on cytoscopy coincident with a 6 log fall in urine BK viral load. Only non-responder was a patient with BK infection whose line lacked activity for this virus, likely reflecting the serostatus of the donor. In addition, 3 patients subsequently reactivated other viruses than those for which they were initially treated, but all cleared these infections by week 12, without the requirement for additional cell infusions (CMV: 1CR; EBV: 1CR; BK: 1CR; HHV6: 1CR). Finally, 1 patient received multivirus specific VSTs under a single patient protocol as an emergency treatment for widespread and bulky rituximab-resistant EBV-PTLD. Post VST treatment there was an immediate decline in the patient's EBV viral load with complete and sustained resolution of PTLD, coincident with an increase in circulating EBV-specific T cells. However, the profound anti-tumor activity mediated by the rapidly-expanding EBV-directed T cells also produced a transient systemic inflammatory response syndrome, which was controlled with steroids and anti-TNFR antibody, with no long term adverse effects.
Thus, infusion of donor-derived, multivirus specific VSTs generated with clinical grade pepmixes and infused either prophylactically or as treatment for one or more viral infections has been safe and is associated with the appearance of virus-reactive T cells in peripheral blood that have been able to control infection with above mentioned viruses.
- Conditions
- Viral Infections After HSCT
- Being tested
- VSTs
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VSTsBiological
most closely HLA-matched multivirus-specific T cell lines obtained from a bank of allogeneic virus-specific T cell lines (VSTs) have antiviral activity against three viruses: EBV, CMV and adenovirus
| Study group | Role | What they receive |
|---|---|---|
| VSTs against three viruses | Experimental | Patients will receive 2 x 107 partially HLA-matched VSTs/m2 as a single infusion. In the rare case where insufficient banked cell product is available, a lower number of cells may be infused after discussion with the principal investigator, patient and/or guardian and the treatment team. If participants have a partial response (as defined by a 50% fall in viral load) they are eligible to receive up to 4 additional doses from day 28 after the initial infusion and at 2 weekly intervals thereafter. Receives: Biological: VSTs |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessments of patients with adverse events after VSTs infusion.
Safety of administration of VSTs is 45 days for GVHD. The safety endpoint will be defined as acute GvHD grades III-IV related to the T cell product within 45 days of the last VST dose and that are not due to the pre-existing infection or the original malignancy or pre-existing co-morbidities as defined by the NCI Common Terminology Criteria for Adverse Events (CTCAE)
Measured: 45 days
Secondary outcomes (2)
Assessments of viral load response to the CTL infusion
Increase in viral load of at least 50% from baseline or dissemination to other sites of disease.
Measured: 12 months
Assessments of Antiviral Immunity
Patient serum and peripheral blood mononuclear cells will be monitored for virus-specific activity by phenotypic and functional studies including ELIspot with appropriate viral specific peptide mixtures and available HLA-restricted epitope peptides, intracellular cytokine staining, serum cytokine profiling and/or other assays as they become available for immune profiling purposes.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2015 (estimated)
- Study start28 Oct 2014
- Primary completion11 Sep 2017
- Study completion3 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Viral Infections After HSCTStudies of the same condition, open and under way.
- 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
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Catherine Bollard
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Catherine Bollard, Children's National Research Institute
- Investigators
- Catherine Bollard, MD, Principal investigator, Children's National Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02510417
- Sponsor's protocol ID
- CHAPS
- Status last verified
- Jul 2025
- First submitted
- 13 Jul 2015
- Last updated
- 2 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Administration of Most Closely HLA-matched Multivirus-specific Cytotoxic T-Lymphocytes for the Treatment of EBV, CMV, Adenovirus Infections Post Allogeneic Stem Cell Transplant
- ClinicalTrials.gov ID
- NCT02510417
- Acronym / sponsor ID
- CHAPS
- Conditions
- Viral Infections After HSCT
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Catherine BollardUniversity, hospital or other
- Study start
- 28 Oct 2014 (actual)
- Primary completion
- 11 Sep 2017 (actual)
- Study completion
- 3 Jan 2018 (actual)
- First posted
- 29 Jul 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of the study is to evaluate whether most closely HLA-matched multivirus-specific T cell lines obtained from a bank of allogeneic virus-specific T cell lines (VSTs) have antiviral activity against three viruses: EBV, CMV and adenovirus.
Reconstitution of anti-viral immunity by donor-derived VSTs has shown promise in preventing and treating infections associated with CMV, EBV and adenovirus post-transplant. However, the time taken to prepare patient-specific products and lack of virus-specific memory T cells in cord blood and seronegative donors, limits their value.
An alternative is to use banked partially HLA-matched allogeneic VSTs. A prior phase II study at our institution using trivirus-specific VSTs generated using monocytes and EBV-transformed B cells gene-modified with a clinical grade adenoviral vector expressing CMV-pp65 to activate and expand specific T cells showed the feasibility, safety and activity of this approach for the treatment of refractory CMV, EBV and Adenovirus infections. However, the production process was lengthy, requiring 8-12 weeks, with exposure to biohazards (B95.8 EBV viral strain and adenovector), while antigenic competition between different viral components precluded increasing the spectrum of specificity beyond these three viruses.
Investigator have overcome these limitations and in the current trial, they will evaluate whether rapidly generated, allogeneic most closely HLA-matched multivirus-specific VSTs, activated using overlapping peptide libraries spanning immunogenic antigens from CMV, adenovirus and EBV will be safe and produce anti-viral effects in allogeneic HSCT recipients infected with one of more of the targeted viruses that are persistent despite conventional anti-viral therapy. The study agent will be assessed for safety (stopping rules defined) and antiviral activity.
Detailed description
Investigators evaluated the clinical utility of Multivirus VSTs in recipients of matched related, matched unrelated, or haploidentical donor transplants. To date, 10 clinical-grade multivirus-directed VSTs have been generated from donor PBMCs. These lines were polyclonal, comprising both CD4+ (57±5%) and CD8+ (35±5%) cells and retained expression of the memory markers CD45RO+CD62L+ (58±8%). Their specificity was dependent on the prior viral exposure of the cell donor; 7/8 tested lines had activity against Adv,8/8 against CMV, 6/8 against EBV. None of the lines reacted against recipient PHA blasts - indicating lack of alloreactive potential in these rapidly generated lines.
Investigators administered these multivirus-specific donor-derived VSTs to 3 allogeneic HSCT recipients in a dose escalation study all on DL1 (5x106/m2). There were no immediate infusion toxicities, and no de novo acute GvHD, demonstrating the in vivo safety of these mVST. Further, antiviral efficacy has been observed in 1 patient with refractory CMV. In addition, in a recently published paper from Baylor College of Medicien (Anapoulous et al, STM 2014) they have treated VSTs manufactured with a similar methodology, but targeting 5 viruses instead of 3 with specificity to BK virus and HHV6. In that study 10 patients were treated with 4 on DL1 (5x10e6/m2), 4 on DL2 (1x10e7/m2) and 2 on DL3 (2x10e7/m2) and again saw no immediate infusion toxicities, and no de novo acute GvHD, demonstrating the in vivo safety of these mVST. Three patients received the cells as viral prophylaxis (days 38-43 post-HSCT) and none developed viral infections at up to 3 months post-treatment. The other 7 patients received the cells as treatment for one or more active infections between days 59-139 post-HSCT. Based on viral load measurements by day 42 post-infusion, the VSTs were successful in controlling active infections with CMV (1 complete (CR) and 1 partial response (PR)), EBV (2 CRs, including a case of frank PTLD); Adv (1 CR); HHV6 (1 CR); and BK (3 CR, 1 PR, 1NR). Of note, 3 BK virus responders had tissue disease with severe hemorrhagic cystitis and all had marked improvement or disappearance of hematuria following infusion. One patient subsequently had an episode of transient but severe bladder pain in association with inflammation seen on cytoscopy coincident with a 6 log fall in urine BK viral load. Only non-responder was a patient with BK infection whose line lacked activity for this virus, likely reflecting the serostatus of the donor. In addition, 3 patients subsequently reactivated other viruses than those for which they were initially treated, but all cleared these infections by week 12, without the requirement for additional cell infusions (CMV: 1CR; EBV: 1CR; BK: 1CR; HHV6: 1CR). Finally, 1 patient received multivirus specific VSTs under a single patient protocol as an emergency treatment for widespread and bulky rituximab-resistant EBV-PTLD. Post VST treatment there was an immediate decline in the patient's EBV viral load with complete and sustained resolution of PTLD, coincident with an increase in circulating EBV-specific T cells. However, the profound anti-tumor activity mediated by the rapidly-expanding EBV-directed T cells also produced a transient systemic inflammatory response syndrome, which was controlled with steroids and anti-TNFR antibody, with no long term adverse effects.
Thus, infusion of donor-derived, multivirus specific VSTs generated with clinical grade pepmixes and infused either prophylactically or as treatment for one or more viral infections has been safe and is associated with the appearance of virus-reactive T cells in peripheral blood that have been able to control infection with above mentioned viruses.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| VSTs against three viruses | Experimental | Biological: VSTsPatients will receive 2 x 107 partially HLA-matched VSTs/m2 as a single infusion. In the rare case where insufficient banked cell product is available, a lower number of cells may be infused after discussion with the principal investigator, patient and/or guardian and the treatment team. If participants have a partial response (as defined by a 50% fall in viral load) they are eligible to receive up to 4 additional doses from day 28 after the initial infusion and at 2 weekly intervals thereafter. |
Who may qualify
- Ages
- 4 weeks to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- Received prior myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplant using either bone marrow, single/double cord blood or PBSC
- Cells administered as;
- Steroids less or equal to 0.5 mg/kg/day prednisone
- 5)Bilirubin <3x, AST <3x, Serum creatinine <2x upper limit of normal, Hgb >8.0, plts >20 6) Pulse oximetry of > 90% on room air 7) Available VSTs 8) Negative pregnancy test (if female of childbearing potential after reduced intensity conditioning) 9) Patient or parent/guardian capable of providing informed consent.
Key exclusion criteria (5 listed)
- Received ATG, Campath or other T cell immunosuppressive monoclonal antibodies in the last 28 days.
- Patients with other uncontrolled infections
- Received donor lymphocyte infusion in last 28 days
- Evidence of GVHD > or equal to grade 2
- Active and uncontrolled relapse of malignancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VSTsmost closely HLA-matched multivirus-specific T cell lines obtained from a bank of allogeneic virus-specific T cell lines (VSTs) have antiviral activity against three viruses: EBV, CMV and adenovirus | Biological | VSTs against three viruses |
Primary outcome
Assessments of patients with adverse events after VSTs infusion.
Time frame: 45 days
Safety of administration of VSTs is 45 days for GVHD. The safety endpoint will be defined as acute GvHD grades III-IV related to the T cell product within 45 days of the last VST dose and that are not due to the pre-existing infection or the original malignancy or pre-existing co-morbidities as defined by the NCI Common Terminology Criteria for Adverse Events (CTCAE)
2 secondary outcomes
Assessments of viral load response to the CTL infusion
Time frame: 12 months
Assessments of Antiviral Immunity
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2025.
Related trials for Viral Infections After HSCT
Not yet recruitingEarly Phase 1
25BT056: Basket Study of Viral Cytotoxic T Lymphocytes
EBV Viremia, CMV Viremia
Active, not recruitingObservational study
Infection Prophylaxis and Management in Treating Cytomegalovirus (CMV) Infection in Patients With Hematologic Malignancies Previously Treated With Donor Stem Cell Transplant
Hematopoietic/Lymphoid Cancer, Accelerated Phase Chronic Myelogenous Leukemia
RecruitingPhase 3
A Phase 3 Study of Tabelecleucel for Participants With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease After Failure With Rituximab or Rituximab and Chemotherapy
Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Solid Organ Transplant Complications
RecruitingPhase 3
A Phase 3 Trial to Compare IV BCV Versus IV CDV for Treatment of Adenovirus Infection After Allo-HCT
Adenovirus Infections
Active, not recruitingPhase 1
Multi-virus CTLs Expressing CD19 Chimeric Receptors, CD19 Positive Malignancies Post SCT, MULTIPRAT
Acute Lymphoblastic Leukemia (ALL), Chronic Lymphocytic Leukemia (CLL)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Catherine Bollard, MD principal investigator
Children's National Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing VSTs in people with Viral Infections After HSCT, run by Catherine Bollard at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessments of patients with adverse events after VSTs infusion. (time frame: 45 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2025.