Post-transplant Lymphoproliferative DiseaseEarly Phase 1ITRECNCT03131934
Immunotherapy With Tacrolimus Resistant EBV CTL for Lymphoproliferative Disease After Solid Organ Transplant
A Early Phase 1 study testing Autologous EBV-CTL transduced with vector SFG-CNA12 and Leucapheresis in people with Post-transplant Lymphoproliferative Disease and Transplant-Related Hematologic Malignancy, run by University College, London at 2 sites in United Kingdom.
Trial summary
This is an open label, non-randomised, multicentre Phase I to determine the safety of tacrolimus-resistant autologous EBV-specific cytotoxic T-cells (EBV CTL) and compare their expansion/persistence with control EBV CTL in solid organ transplant patients with post-transplant lymphoproliferative disease (PTLD). Read more about this study
- Who is it for?
- Ages 1 year to 70 years
- Conditions the study is for
- Post-transplant Lymphoproliferative Disease, Transplant-Related Hematologic Malignancy
- What is being tested?
- Autologous EBV-CTL transduced with vector SFG-CNA12 and Leucapheresis
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 31 May 2019to 12 Mar 2026
- Phase
- Early 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 1 year to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Adult and paediatric (age 1-70 years) solid organ transplant recipients with histologically proven B-lineage EBV+ post-transplant lymphoproliferative disease (PTLD) either de novo or resistant to Rituximab
- EBV viraemia at enrolment
- On immunosuppression with tacrolimus
- Agreement to have a pregnancy test and use of contraception for duration of trial (if applicable)
- Written informed consent
Who cannot join
- Fulminant disease
- Requirement for supplemental oxygen
- Burkitt's lymphoma/Mature B-acute lymphoblastic leukaemia with IgH-Myc rearrangement
- T-lineage PTLD
- Bilirubin > 3 x upper limit of normal
- Creatinine > 3 x upper limit of normal
Show all 10Show fewer
- Active hepatitis B, C or HIV infection
- Women who are pregnant or breast-feeding
- ECOG performance score ≥ 4
- Inability to tolerate leucapheresis
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
Great Ormond Street Hospital
London
King's College Hospital
London
About this study
This is an open label, non-randomised, multicentre Phase I to determine the safety of tacrolimus-resistant autologous EBV-specific cytotoxic T-cells (EBV CTL) and compare their expansion/persistence with control EBV CTL in solid organ transplant patients with post-transplant lymphoproliferative disease (PTLD). Each patient will receive an infusion of two ATIMPs - autologous EBV CTL retrovirally transduced with (a) a calcineurin mutant (CNA12) that confers resistance to tacrolimus and (b) a control calcineurin mutant (CNA8).
Read the detailed description
This is a multi-centre, non-randomised, open label Phase 1 clinical trial of Advanced Therapy Investigational Medicinal Products (ATIMPs) in adult and paediatric (age 1-70 years) solid organ transplant recipients with histologically proven B-lineage EBV+ post-transplant lymphoproliferative disease (PTLD).
The ATIMPs for this study are autologous EBV CTL transduced with the (a) the retroviral vector SFG-CNA12 encoding a calcineurin A mutant (CNA12) that confers resistance to tacrolimus and (b) the retroviral vector SFG-CNA8 encoding a control calcineurin A mutant (CNA8).
Following informed consent and registration to the trial, patients will undergo an unstimulated leucapheresis for generation of both ATIMPs. Patients will receive an equal dose of each ATIMP (10x7 CNA8+ or CNA12+ CTL/m2) which will be administered intravenously.
Other immunosuppressants (e.g. MMF) will be reduced, but tacrolimus will be maintained at therapeutic levels.The trial will evaluate the safety of the ATIMPs in organ transplant recipients developing EBV+ PTLD and compare the persistence and frequency of circulating CNA12 and CNA8 CTL in the peripheral blood.
Our hypothesis is that in the presence of ongoing immunosuppression with tacrolimus, CNA12 CTL will show preferential expansion and prolonged persistence compared with CNA8 CTL. If successful this will result in durable clearance of PTLD without the need to reduce tacrolimus, thus reducing the risk of graft rejection.
Patients will be followed up regularly during the interventional phase of the study until 1 year post EBV CTL infusion. During the long-term follow-up phase of the study (from 1-5 years post EBV CTL infusion) patients will be followed up annually.
- Being tested
- Autologous EBV-CTL transduced with vector SFG-CNA12, Autologous EBV-CTL transduced with control vector SFG-CNA8, Leucapheresis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous EBV-CTL transduced with vector SFG-CNA12Biological
Autologous EBV-specific cytotoxic T-cells (CTL) transduced with the retroviral vector SFG-CNA12 conferring resistance to tacrolimus
Autologous EBV-CTL transduced with control vector SFG-CNA8Biological
Autologous EBV-specific cytotoxic T-cells (CTL) transduced with the control retroviral vector SFG-CNA8
LeucapheresisProcedure or surgery
Patients will undergo an unstimulated leucapheresis to isolate the required immune cells to produce the EBV-CTLs
| Study group | Role | What they receive |
|---|---|---|
| Autologous EBV-CTL transduced with SFG-CNA12/SFG-CNA8 | Experimental | All patients will receive the autologous EBV CTL retrovirally transduced with with (a) a calcineurin mutant (CNA12) that confers resistance to tacrolimus and (b) a control calcineurin mutant (CNA8). For each patient two ATIMPs will be generated:
* Autologous EBV-specific cytotoxic T-cells (CTL) transduced with the retroviral vector SFG-CNA12
* Autologous EBV-specific cytotoxic T-cells (CTL) transduced with the control retroviral vector SFG-CNA8
An equal dose (10x7/m2) of CNA12+ EBV CTL and CNA8+ EBV CTL will be administered intravenously on day 0.
While awaiting ATIMP generation, patients may receive a single dose of Rituximab and other immunosuppressants (e.g. MMF) will be reduced, but tacrolimus will be maintained at therapeutic levels. Receives: Biological: Autologous EBV-CTL transduced with vector SFG-CNA12; Biological: Autologous EBV-CTL transduced with control vector SFG-CNA8; Procedure: Leucapheresis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicity at 6 weeks post infusion
Toxicity as assessed by NCI Common toxicity criteria within 6 weeks of infusion
Measured: 6 weeks
Persistence and frequency of circulating EBV CTL
Persistence and frequency of circulating EBV CTL transduced with CNA12 compared with control vector CNA8 in the peripheral blood
Measured: 12 months
Secondary outcomes (4)
Disease response
Disease response at 6 weeks
Measured: 6 weeks
Relapse rate
Relapse rate at 1 and 2 years
Measured: 2 years
Disease free survival
Disease free survival at 1 and 2 yrs
Measured: 2 years
Organ graft Rejection
Organ graft Rejection at 1 and 2 yrs
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2017
- Study start31 May 2019
- Primary completion30 Jun 2020
- Study completion12 Mar 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post-transplant Lymphoproliferative DiseaseStudies of the same condition, open and under way.
- More trials run by University College, LondonThe 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
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Collaborators
- Genetix Biotherapeutics Inc.
- Responsible party
- Sponsor
- Investigators
- Prof. Persis Amrolia, Principal investigator, Great Ormond Street Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03131934
- Sponsor's protocol ID
- UCL/16/0529
- Acronym
- ITREC
- Status last verified
- Aug 2026
- First submitted
- 24 Apr 2017
- Last updated
- 7 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunotherapy With Tacrolimus Resistant EBV CTL for Lymphoproliferative Disease After Solid Organ Transplant
- ClinicalTrials.gov ID
- NCT03131934
- Acronym / sponsor ID
- ITREC / UCL/16/0529
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Collaborators
- Genetix Biotherapeutics Inc.
- Study start
- 31 May 2019 (actual)
- Primary completion
- 30 Jun 2020 (actual)
- Study completion
- 12 Mar 2026 (actual)
- First posted
- 27 Apr 2017 (actual)
- 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.
This is an open label, non-randomised, multicentre Phase I to determine the safety of tacrolimus-resistant autologous EBV-specific cytotoxic T-cells (EBV CTL) and compare their expansion/persistence with control EBV CTL in solid organ transplant patients with post-transplant lymphoproliferative disease (PTLD). Each patient will receive an infusion of two ATIMPs - autologous EBV CTL retrovirally transduced with (a) a calcineurin mutant (CNA12) that confers resistance to tacrolimus and (b) a control calcineurin mutant (CNA8).
Detailed description
This is a multi-centre, non-randomised, open label Phase 1 clinical trial of Advanced Therapy Investigational Medicinal Products (ATIMPs) in adult and paediatric (age 1-70 years) solid organ transplant recipients with histologically proven B-lineage EBV+ post-transplant lymphoproliferative disease (PTLD).
The ATIMPs for this study are autologous EBV CTL transduced with the (a) the retroviral vector SFG-CNA12 encoding a calcineurin A mutant (CNA12) that confers resistance to tacrolimus and (b) the retroviral vector SFG-CNA8 encoding a control calcineurin A mutant (CNA8).
Following informed consent and registration to the trial, patients will undergo an unstimulated leucapheresis for generation of both ATIMPs. Patients will receive an equal dose of each ATIMP (10x7 CNA8+ or CNA12+ CTL/m2) which will be administered intravenously.
Other immunosuppressants (e.g. MMF) will be reduced, but tacrolimus will be maintained at therapeutic levels.The trial will evaluate the safety of the ATIMPs in organ transplant recipients developing EBV+ PTLD and compare the persistence and frequency of circulating CNA12 and CNA8 CTL in the peripheral blood.
Our hypothesis is that in the presence of ongoing immunosuppression with tacrolimus, CNA12 CTL will show preferential expansion and prolonged persistence compared with CNA8 CTL. If successful this will result in durable clearance of PTLD without the need to reduce tacrolimus, thus reducing the risk of graft rejection.
Patients will be followed up regularly during the interventional phase of the study until 1 year post EBV CTL infusion. During the long-term follow-up phase of the study (from 1-5 years post EBV CTL infusion) patients will be followed up annually.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Autologous EBV-CTL transduced with SFG-CNA12/SFG-CNA8 | Experimental | Biological: Autologous EBV-CTL transduced with vector SFG-CNA12, Biological: Autologous EBV-CTL transduced with control vector SFG-CNA8, Procedure: LeucapheresisAll patients will receive the autologous EBV CTL retrovirally transduced with with (a) a calcineurin mutant (CNA12) that confers resistance to tacrolimus and (b) a control calcineurin mutant (CNA8). For each patient two ATIMPs will be generated: * Autologous EBV-specific cytotoxic T-cells (CTL) transduced with the retroviral vector SFG-CNA12 * Autologous EBV-specific cytotoxic T-cells (CTL) transduced with the control retroviral vector SFG-CNA8 An equal dose (10x7/m2) of CNA12+ EBV CTL and CNA8+ EBV CTL will be administered intravenously on day 0. While awaiting ATIMP generation, patients may receive a single dose of Rituximab and other immunosuppressants (e.g. MMF) will be reduced, but tacrolimus will be maintained at therapeutic levels. |
Who may qualify
- Ages
- 1 year to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Adult and paediatric (age 1-70 years) solid organ transplant recipients with histologically proven B-lineage EBV+ post-transplant lymphoproliferative disease (PTLD) either de novo or resistant to Rituximab
- EBV viraemia at enrolment
- On immunosuppression with tacrolimus
- Agreement to have a pregnancy test and use of contraception for duration of trial (if applicable)
- Written informed consent
Key exclusion criteria (10 listed)
- Fulminant disease
- Requirement for supplemental oxygen
- Burkitt's lymphoma/Mature B-acute lymphoblastic leukaemia with IgH-Myc rearrangement
- T-lineage PTLD
- Bilirubin > 3 x upper limit of normal
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 |
|---|---|---|
| Autologous EBV-CTL transduced with vector SFG-CNA12Autologous EBV-specific cytotoxic T-cells (CTL) transduced with the retroviral vector SFG-CNA12 conferring resistance to tacrolimus | Biological | Autologous EBV-CTL transduced with SFG-CNA12/SFG-CNA8 |
| Autologous EBV-CTL transduced with control vector SFG-CNA8Autologous EBV-specific cytotoxic T-cells (CTL) transduced with the control retroviral vector SFG-CNA8 | Biological | Autologous EBV-CTL transduced with SFG-CNA12/SFG-CNA8 |
| LeucapheresisPatients will undergo an unstimulated leucapheresis to isolate the required immune cells to produce the EBV-CTLs | Procedure or surgery | Autologous EBV-CTL transduced with SFG-CNA12/SFG-CNA8 |
Primary outcome
Toxicity at 6 weeks post infusion
Time frame: 6 weeks
Toxicity as assessed by NCI Common toxicity criteria within 6 weeks of infusion
Persistence and frequency of circulating EBV CTL
Time frame: 12 months
Persistence and frequency of circulating EBV CTL transduced with CNA12 compared with control vector CNA8 in the peripheral blood
4 secondary outcomes
Disease response
Time frame: 6 weeks
Relapse rate
Time frame: 2 years
Disease free survival
Time frame: 2 years
Organ graft Rejection
Time frame: 2 years
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 7 Aug 2026.
- Individual participant dataSharing planned: Undecided
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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.
Prof. Persis Amrolia principal investigator
Great Ormond Street Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Autologous EBV-CTL transduced with vector SFG-CNA12 and Leucapheresis in people with Post-transplant Lymphoproliferative Disease and Transplant-Related Hematologic Malignancy, run by University College, London at 2 sites in United Kingdom.
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 5 inclusion and 10 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 7 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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?
Toxicity at 6 weeks post infusion (time frame: 6 weeks). The study lists 2 primary outcomes in all. 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 7 Aug 2026.