CD19+ Malignancies: Relapse Post-allogeneic TransplantPhase 1CARDNCT02893189
CAR19 Donor Lymphocytes for Relapsed CD19+ Malignancies Following Allogeneic Transplantation
A Phase 1 study testing Infusion of modified CAR19 T-cells (4G7-CARD T-cells) in people with CD19+ Malignancies: Relapse Post-allogeneic Transplant, run by University College, London at 1 site in United Kingdom.
Trial summary
Eligible patients will receive escalating doses of 4G7-CARD T-cells paralleling clinical standard of care with unmanipulated donor lymphocytes. There are 3 intra-patient dose levels planned. Read more about this study
- Who is it for?
- Ages 16 to 70 years
- Conditions the study is for
- CD19+ Malignancies: Relapse Post-allogeneic Transplant
- What is being tested?
- Infusion of modified CAR19 T-cells (4G7-CARD T-cells)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 27 Apr 2017to 31 Dec 2022
- 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 16 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age 16-70 years
- Confirmed diagnosis of CD19+ malignancy relapsing following allogeneic transplantation
- Agreement to have a pregnancy test, use adequate contraception for 12 months post-final 4G7-CARD T-cell infusion
- Karnofsky performance status >60
- Written informed consent
Who cannot join
- Women who are pregnant or lactating
- Prior history of ischaemic heart disease, dysrhythmias, abnormal ECG (LBBB), Multi Gated Acquisition Scan (MUGA) left ventricular ejection fraction (LVEF<40%) (if performed)
- Known involvement of the central nervous system or cerebral vascular accident within prior 3 months
- Patients receiving corticosteroids at a dose of > 10mg prednisolone per day (or equivalent)
- Active graft versus host disease requiring immunosuppression
- Use of rituximab within the last 2 months prior to ATIMP infusion
- Known allergy to albumin or dimethyl sulfoxide (DMSO)
- Patients who have experienced significant neurotoxicity following blinatumomab treatment
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Chimeric Antigen Receptor (CAR)19 Donor Lymphocytes for Relapsed Cluster of Differentiation (CD)19+ Malignancies Following Allogeneic Transplantation (CARD)
Eligible patients will receive escalating doses of 4G7-CARD T-cells paralleling clinical standard of care with unmanipulated donor lymphocytes. There are 3 intra-patient dose levels planned.
Patients will be followed up regularly during the interventional phase of the study until 12 months post-final 4G7-CARD T-cell infusion. Thereafter patients will be followed up annually for years 2 and 3.
Read the detailed description
Patients will receive escalating doses of 4G7-CARD T-cells (after pre-conditioning with Fludarabine and Cyclophosphamide), paralleling clinical standard of care with unmanipulated donor lymphocytes. Intra-patient dose escalation will proceed at intervals of not less than 8 weeks, dependent on development of toxicity or evidence of efficacy and confirmation by the Trial Management Group.
Three dose cohorts levels are planned, and dosing will be according to total CD3+ T- cell dose as this correlates with toxicity in the unmanipualated donor lymphocyte setting:
- Dose Level 1: 1x10^6 CD3+ T-cells/kg (starting dose for all patients)
- Dose Level 2: 3x10^6 CD3+ T-cells/kg
- Dose Level 3: 1x10^7 CD3+ T-cells/kg
The inter-patient dosing for the first 3 patients was at least 28 days, following TMG confirmation.
Patients will be followed up regularly during the interventional phase of the study until 12 months post-final 4G7-CARD T-cell infusion. During the long term follow up phase of the study (years 2-3 post-final 4G7-CARD T-cell infusion) patients will be followed-up annually for overall survival, disease status and safety.
All patients will enter long term follow up until 3 years post-final 4G7-CARD T-cell infusion.
- Being tested
- Infusion of modified CAR19 T-cells (4G7-CARD T-cells)
- Keywords
- CD19+, allogeneic transplant, relapse
- Medical subject headings
- Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Infusion of modified CAR19 T-cells (4G7-CARD T-cells)Genetic
The original stem cells donor (or if not available the patient) will undergo unstimulated leucapheresis for generation of the Advanced Therapy Interventional Medicinal Product (ATIMP) 4G7-CARD T-cells. Escalating doses of the ATIMP will then be infused to the patient depending on outcome and any experienced side effects.
| Study group | Role | What they receive |
|---|---|---|
| 4G7-CARD T-cells | Experimental | All patient will receive modified CAR19 T-cells. Receives: Genetic: Infusion of modified CAR19 T-cells (4G7-CARD T-cells) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility of generation of 4G7-CARD T-cells using the ProdigyTM system
The number of ATIMP successfully manufactured would be assessed for all registered patients
Measured: Through patient registration and manufacturing period, an average of 18 months from start of trial
Maximum grade for each toxicity type as assessed by CTCAE v4.03, summarized as proportions.
Toxicity evaluation following 4G7-CARD T-cell administration as evaluated by the occurrence of adverse events per studied dose using CTCAE v4.03, defined as >grade 2 events that are causally related to study treatment or procedure or Serious Adverse Reactions that require withdrawal of the patient from the study; development and severity of graft-versus-host-disease (GvHD) following cell infusion will also be evaluated as a potential toxicity, as well as development and severity of cytokine release syndrome / macrophage activation syndromes assessed by 'University of Pennsylvania' criteria
Measured: Up to 3 years post final 4G7-CARD T-cell infusion
Secondary outcomes (3)
Assessment of engraftment, expansion and persistence of the 4G7-CARD T-cells as determined by quantitative polymerase chain reaction (qPCR) or flow cytometry
Data for engraftment and expansion would be summarised by mean, median or interquartile ranges and a Kaplan Meier plot for persistence
Measured: Sampling occurs at days 0, 4, 6, 11, 18, plus months 1, 2, 3, 6, 9 and 1 year post final 4G7-CARD T-cell infusion
Assessing the depletion of B cell compartment, as determined by flow cytometry
Data would be summarised using means (medians) and as the percentage reduction from baseline
Measured: Sampling occurs at days 0, 4, 6, 11, 18, plus months 1, 2, 3, 6, 9 and 1 year post final 4G7-CARD T-cell infusion
Assessing the timing and magnitude of cytokine release, evaluated using Cytokine bead arrays
Data on timing (kinetic of change) and magnitude of cytokine levels can be summarised using means (medians) and plots for each patients
Measured: Sampling occurs at days 0, 4, 6, 11, 18, plus 1 month post final 4G7-CARD T-cell infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2016 (estimated)
- Study start27 Apr 2017
- Primary completion31 Dec 2019
- Study completion31 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for CD19+ Malignancies: Relapse Post-allogeneic TransplantStudies 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
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Karl Peggs, Principal investigator, University College London Hospitals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02893189
- Sponsor's protocol ID
- UCL16/0045
- Acronym
- CARD
- Status last verified
- Jun 2023
- First submitted
- 17 May 2016
- Last updated
- 22 Jun 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Krawczyk M, Druzynska M, Bednarska E, Winiarska M. The race between 4-1BB- and CD28-based CD19 CAR-T products in the therapy of B-cell malignancies. Biochim Biophys Acta Rev Cancer. 2026 Feb;1881(1):189519. doi: 10.1016/j.bbcan.2025.189519. Epub 2025 Dec 20.
PubMed 41429239Roddie C, Dias J, O'Reilly MA, Abbasian M, Cadinanos-Garai A, Vispute K, Bosshard-Carter L, Mitsikakou M, Charalambous E, Mehra V, Roddy H, Cheung GW, Hartley JA, Mahmoud N, Ensell L, Patel Y, Marzolini MAV, Farzaneh F, Nickolay L, Himoudi N, Syed F, Popova B, Galani S, Day A, Lowdell MW, Peggs KS. Matched donor allogeneic CAR-T for adult B-ALL: toxicity, efficacy, repeat dosing, and the importance of lymphodepletion. Blood. 2025 Oct 2;146(14):1664-1676. doi: 10.1182/blood.2025028790.
PubMed 40643148O'Reilly M, Roddie C, Marzolini MAV, Rodriguez-Justo M, Pomplun S, Pule M, Peggs KS. Trafficking of CAR T cells to sites of subclinical leukaemia cutis. Lancet Oncol. 2020 Mar;21(3):e179. doi: 10.1016/S1470-2045(19)30861-7. No abstract available.
PubMed 32135121
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Chimeric Antigen Receptor (CAR)19 Donor Lymphocytes for Relapsed Cluster of Differentiation (CD)19+ Malignancies Following Allogeneic Transplantation (CARD)
- ClinicalTrials.gov ID
- NCT02893189
- Acronym / sponsor ID
- CARD / UCL16/0045
- Keywords
- CD19+, allogeneic transplant, relapse
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Study start
- 27 Apr 2017 (actual)
- Primary completion
- 31 Dec 2019 (actual)
- Study completion
- 31 Dec 2022 (actual)
- First posted
- 8 Sep 2016 (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.
Eligible patients will receive escalating doses of 4G7-CARD T-cells paralleling clinical standard of care with unmanipulated donor lymphocytes. There are 3 intra-patient dose levels planned.
Patients will be followed up regularly during the interventional phase of the study until 12 months post-final 4G7-CARD T-cell infusion. Thereafter patients will be followed up annually for years 2 and 3.
Detailed description
Patients will receive escalating doses of 4G7-CARD T-cells (after pre-conditioning with Fludarabine and Cyclophosphamide), paralleling clinical standard of care with unmanipulated donor lymphocytes. Intra-patient dose escalation will proceed at intervals of not less than 8 weeks, dependent on development of toxicity or evidence of efficacy and confirmation by the Trial Management Group.
Three dose cohorts levels are planned, and dosing will be according to total CD3+ T- cell dose as this correlates with toxicity in the unmanipualated donor lymphocyte setting:
- Dose Level 1: 1x10^6 CD3+ T-cells/kg (starting dose for all patients)
- Dose Level 2: 3x10^6 CD3+ T-cells/kg
- Dose Level 3: 1x10^7 CD3+ T-cells/kg
The inter-patient dosing for the first 3 patients was at least 28 days, following TMG confirmation.
Patients will be followed up regularly during the interventional phase of the study until 12 months post-final 4G7-CARD T-cell infusion. During the long term follow up phase of the study (years 2-3 post-final 4G7-CARD T-cell infusion) patients will be followed-up annually for overall survival, disease status and safety.
All patients will enter long term follow up until 3 years post-final 4G7-CARD T-cell infusion.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 4G7-CARD T-cells | Experimental | Genetic: Infusion of modified CAR19 T-cells (4G7-CARD T-cells)All patient will receive modified CAR19 T-cells. |
Who may qualify
- Ages
- 16 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Age 16-70 years
- Confirmed diagnosis of CD19+ malignancy relapsing following allogeneic transplantation
- Agreement to have a pregnancy test, use adequate contraception for 12 months post-final 4G7-CARD T-cell infusion
- Karnofsky performance status >60
- Written informed consent
Key exclusion criteria (8 listed)
- Women who are pregnant or lactating
- Prior history of ischaemic heart disease, dysrhythmias, abnormal ECG (LBBB), Multi Gated Acquisition Scan (MUGA) left ventricular ejection fraction (LVEF<40%) (if performed)
- Known involvement of the central nervous system or cerebral vascular accident within prior 3 months
- Patients receiving corticosteroids at a dose of > 10mg prednisolone per day (or equivalent)
- Active graft versus host disease requiring immunosuppression
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 |
|---|---|---|
| Infusion of modified CAR19 T-cells (4G7-CARD T-cells)The original stem cells donor (or if not available the patient) will undergo unstimulated leucapheresis for generation of the Advanced Therapy Interventional Medicinal Product (ATIMP) 4G7-CARD T-cells. Escalating doses of the ATIMP will then be infused to the patient depending on outcome and any experienced side effects. | Genetic | 4G7-CARD T-cells |
Primary outcome
Feasibility of generation of 4G7-CARD T-cells using the ProdigyTM system
Time frame: Through patient registration and manufacturing period, an average of 18 months from start of trial
The number of ATIMP successfully manufactured would be assessed for all registered patients
Maximum grade for each toxicity type as assessed by CTCAE v4.03, summarized as proportions.
Time frame: Up to 3 years post final 4G7-CARD T-cell infusion
Toxicity evaluation following 4G7-CARD T-cell administration as evaluated by the occurrence of adverse events per studied dose using CTCAE v4.03, defined as >grade 2 events that are causally related to study treatment or procedure or Serious Adverse Reactions that require withdrawal of the patient from the study; development and severity of graft-versus-host-disease (GvHD) following cell infusion will also be evaluated as a potential toxicity, as well as development and severity of cytokine release syndrome / macrophage activation syndromes assessed by 'University of Pennsylvania' criteria
3 secondary outcomes
Assessment of engraftment, expansion and persistence of the 4G7-CARD T-cells as determined by quantitative polymerase chain reaction (qPCR) or flow cytometry
Time frame: Sampling occurs at days 0, 4, 6, 11, 18, plus months 1, 2, 3, 6, 9 and 1 year post final 4G7-CARD T-cell infusion
Assessing the depletion of B cell compartment, as determined by flow cytometry
Time frame: Sampling occurs at days 0, 4, 6, 11, 18, plus months 1, 2, 3, 6, 9 and 1 year post final 4G7-CARD T-cell infusion
Assessing the timing and magnitude of cytokine release, evaluated using Cytokine bead arrays
Time frame: Sampling occurs at days 0, 4, 6, 11, 18, plus 1 month post final 4G7-CARD T-cell infusion
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 22 Jun 2023.
- Derived from this study: PubMed 41429239Krawczyk M, Druzynska M, Bednarska E, Winiarska M. The race between 4-1BB- and CD28-based CD19 CAR-T products in the therapy of B-cell malignancies. Biochim Biophys Acta Rev Cancer. 2026 Feb;1881(1):189519. doi: 10.1016/j.bbcan.2025.189519. Epub 2025 Dec 20.
- Derived from this study: PubMed 40643148Roddie C, Dias J, O'Reilly MA, Abbasian M, Cadinanos-Garai A, Vispute K, Bosshard-Carter L, Mitsikakou M, Charalambous E, Mehra V, Roddy H, Cheung GW, Hartley JA, Mahmoud N, Ensell L, Patel Y, Marzolini MAV, Farzaneh F, Nickolay L, Himoudi N, Syed F, Popova B, Galani S, Day A, Lowdell MW, Peggs KS. Matched donor allogeneic CAR-T for adult B-ALL: toxicity, efficacy, repeat dosing, and the importance of lymphodepletion. Blood. 2025 Oct 2;146(14):1664-1676. doi: 10.1182/blood.2025028790.
- Derived from this study: PubMed 32135121O'Reilly M, Roddie C, Marzolini MAV, Rodriguez-Justo M, Pomplun S, Pule M, Peggs KS. Trafficking of CAR T cells to sites of subclinical leukaemia cutis. Lancet Oncol. 2020 Mar;21(3):e179. doi: 10.1016/S1470-2045(19)30861-7. No abstract available.
- Individual participant dataSharing planned: Undecided
Related trials for CD19+ Malignancies: Relapse Post-allogeneic Transplant
Active, not recruitingPhase 1
Activated T Lymphocytes Expressing CARs, Relapsed CD19+ Malignancies Post-Allo HSCT(CARPASCIO)
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Recruiting
Bridging Allogeneic Hematopoietic Stem Cell Transplantation or Not After CD19 CAR - T (S1904) Cell Therapy for r/r B-cell Acute Lymphoblastic Leukemia
Relapsed Adult ALL, B-cell Acute Lymphoblastic Leukemia
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.
Karl Peggs principal investigator
University College London Hospitals
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 Infusion of modified CAR19 T-cells (4G7-CARD T-cells) in people with CD19+ Malignancies: Relapse Post-allogeneic Transplant, run by University College, London at 1 site 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 8 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 22 Jun 2023. 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 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?
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?
Feasibility of generation of 4G7-CARD T-cells using the ProdigyTM system (time frame: Through patient registration and manufacturing period, an average of 18 months from start of trial). 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?
On the ClinicalTrials.gov record for NCT02893189, which also lists 3 linked publications.
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 22 Jun 2023.