CAR T cells to fight T cell leukaemia
| ISRCTN | ISRCTN15323014 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN15323014 |
| ClinicalTrials.gov (NCT) | NCT05397184 |
| Clinical Trials Information System (CTIS) | 2021-004312-25 |
| Integrated Research Application System (IRAS) | 1004379 |
| Protocol serial number | 19IC17, IRAS 1004379 |
| Sponsor | Great Ormond Street Hospital |
| Funder | Medical Research Council |
- Submission date
- 11/01/2022
- Registration date
- 06/04/2022
- Last edited
- 09/01/2026
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Plain English summary of protocol
Background and study aims
T-cell leukaemia is an uncommon type of blood cell cancer that affects white blood cells (T cells). This phase I clinical trial will treat patients aged 6 months and above with T cell leukaemia which has come back (relapsed) after chemotherapy or is not responding to chemotherapy (refractory). The cell therapy is made from white blood cells (T cells) collected from a healthy donor and changed so they can kill other T cells, including leukaemia cells. These ‘ready-made’ CAR T cells have been made using a new technique called CRISPR base editing to modify their DNA code and have been given the name BE CAR-7. This technique allows them to work after chemotherapy and also disarms them to prevent effects against normal cells. The main aim of this study is to assess the safety of the BE CAR-7 treatment and to see if ready-made CAR T cells can eradicate T cell leukaemia ahead of a planned bone marrow transplant.
Who can participate?
Patients aged 6 months and above with relapsed/refractory T cell leukaemia ahead of a planned bone marrow transplant.
What does the study involve?
Patients will undergo careful screening to confirm that this treatment is adequate for them. Chemotherapy will be given prior to BE CAR-7 infusion to improve the ability of T-cells to establish and grow. Patients will then receive a single infusion of the BE CAR-7 cells and will be closely monitored in hospital. Patients are expected to be in hospital for 4-6 weeks for the BE CAR-7 treatment and the transplant will be scheduled 2-4 weeks after the end of BE CAR7 if leukaemia cells are no longer detectable. Patients will be monitored on the study for 1 year after transplant and then long term in routine clinics.
What are the possible benefits and risks of participating?
Taking part in the study of testing ‘ready-made’ CAR T cells could help reduce the amount of disease and get the patient into remission before a bone marrow transplant. Leukaemia is less likely to come back after a bone marrow transplant if levels in the bone marrow are undetectable. The ready-made CAR T cells are being used to try and improve the chances of successful transplantation. Side effects may include low blood cell counts, infections, cytokine storm (severe immune reaction), graft versus host disease (where the donated cells attack the body) and other complications.
Where is the study run from?
Great Ormond Street Hospital (UK)
When is the study starting and how long is it expected to run for?
January 2022 to May 2028
Who is funding the study?
1. Medical Research Council (MRC) (UK)
2. King's College Hospital (UK)
Who is the main contact?
1. Prof. Waseem Qasim, Waseem.Qasim@gosh.nhs.uk
2. Faizal Shaikh, f.shaikh@ucl.ac.uk
3. Batoul Ahmed, batoul.ahmed@gosh.nhs.uk
Plain English summary under review with external organization
Contact information
Principal investigator, Scientific
30 Guilford Street
London
WC1N 1EH
United Kingdom
 ORCID ID |
0000-0001-8353-4494 |
|---|---|
| Phone | +44 (0)207 405 9200 |
| Waseem.Qasim@gosh.nhs.uk |
Scientific
UCL Great Ormond Street Institute of Child Health
30 Guilford Street
London
WC1N 1EH
United Kingdom
| Phone | +44 (0)203 978 3770 |
|---|---|
| f.shaikh@ucl.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Single-arm non-randomized study |
| Secondary study design | Non randomised study |
| Scientific title | Phase I study of base edited CAR7 T cells to treat T cell malignancies (TvT CAR7) |
| Study acronym | TvT CAR7 |
| Study objectives | The primary objective is to assess the safety of base edited (BE)-CAR7s in patients experiencing relapsed/refractory CD7+ T-cell acute lymphoblastic leukemia (T-ALL). The secondary objectives of the trial are to determine if BE-CAR7 can mediate remission ahead of allogeneic stem cell transplantation (Allo-SCT). Efficacy endpoints are: Bone marrow will be examined at D28 for disease levels by flow and/or molecular minimal residual disease (MRD). Disease remission is defined as morphological complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) with MRD <10e-3 by flow and/or PCR. There are additional exploratory objectives: 1. To assess disease-free survival and overall survival. 2. To assess the time to remission and duration of remission/progression 3. To follow the immune recovery of patients after allogeneic hematopoietic stem cell transplantation (alloHSCT) 4. To track the expansion, persistence and elimination of BE-CAR7 5. To monitor for possible genotoxic side effects from BE modification 6. To record complications following BE-CAR7 treatment |
| Ethics approval(s) |
Approved 29/03/2022, London - West London & GTAC Research Ethics Committee (The Old Chapel, Royal Standard Place, Nottingham, NG1 6FS, United Kingdom; +44 (0)207 104 8007; westlondon.rec@hra.nhs.uk), ref: 22/LO/0001 |
| Health condition(s) or problem(s) studied | Relapsed/refractory T-cell acute lymphoid leukaemia |
| Intervention | Single-dose intravenous infusion (weight-based dosing) of a banded dose of CAR7+ T cells/kg BE-CAR7 Total duration of treatment: 28 days Follow-up: 12 months Patients will undergo careful screening to confirm that this treatment is adequate for them. Chemotherapy will be given prior to BE CAR-7 infusion to improve the ability of T-cells to establish and grow. Patients will then receive a single infusion of the BE CAR-7 cells and will be closely monitored in hospital via blood and bone marrow tests for safety and to check the levels of BE CAR-7 and leukaemia cells. Patients are expected to be in hospital for 4-6 weeks for the BE CAR-7 therapy and the transplant will be scheduled 2-4 weeks after the end of BE CAR7 if leukaemia cells are no longer detectable. Patients will be monitored on the study for 1 year every month for the first 3 months and then every 6 months and then long term in routine clinics. |
| Intervention type | Biological/Vaccine |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | BE-CAR7 |
| Primary outcome measure(s) |
The safety of BE-CAR7s in patients experiencing relapsed/refractory CD7+ T-ALL; measured at baseline, lymphodepletion, day 0, day 28, and additional points for 12 months post bone marrow transplant (BMT) using: |
| Key secondary outcome measure(s) |
Disease remission ahead of allo-SCT measured by bone marrow examination at day 28 for disease levels by flow and/or molecular MRD. Disease remission is defined as morphological complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) with MRD <10e-3 by flow and/or PCR. |
| Completion date | 31/05/2028 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 6 Months |
| Upper age limit | 100 Years |
| Sex | All |
| Target sample size at registration | 10 |
| Total final enrolment | 11 |
| Key inclusion criteria | Current inclusion criteria as of 23/05/2025: Demographic characteristics: 1. Male or female patients 2. Aged 6 months and above Medical and therapeutic criteria: 1. Relapsed/refractory T cell malignancy ahead of planned allogeneic haematopoietic stem cell transplantation (allo-SCT). Morphologically confirmed with leukemic blasts in the bone marrow (>5%) or a quantifiable MRD load (by multiparameter flow cytometry and/or quantitative polymerase chain reaction) 2. CD7+ (>99%) leukaemia-associated immunophenotype (LAIP) 3. Eligible and fit for allogeneic hematopoietic stem cells transplantation with suitable donor available 4. Estimated life expectancy ≥12 weeks 5. Lansky (age <16 years at the time of assent/consent) or Karnofsky (age ≥16 years at the time of assent/consent) performance status ≥70; Eastern Cooperative Oncology Group ECOG performance status <2 Previous inclusion criteria: Demographic characteristics: 1. Male or female patients 2. Age ranging between 6 months and <16 years Medical and therapeutic criteria: 1. Relapsed/refractory T cell malignancy ahead of planned allogeneic haematopoietic stem cell transplantation (allo-SCT). Morphologically confirmed with leukemic blasts in the bone marrow (>5%) or a quantifiable MRD load (by multiparameter flow cytometry and/or quantitative polymerase chain reaction) 2. CD7+ (>99%) leukaemia-associated immunophenotype (LAIP) 3. Eligible and fit for allogeneic hematopoietic stem cells transplantation with suitable donor available 4. Estimated life expectancy ≥12 weeks 5. Lansky (age <16 years at the time of assent/consent) or Karnofsky (age ≥16 years at the time of assent/consent) performance status ≥70; Eastern Cooperative Oncology Group ECOG performance status <2 |
| Key exclusion criteria | 1. Patients/parents unwilling to undergo a follow-up for 15 years 2. Foreseeable poor compliance to the study procedures 3. Evidence of disease progression after cytoreduction 4. Uncontrollable CNS leukaemia or neurological symptoms defined as CNS grade 3 (per National Comprehensive Cancer Network guidelines) 5. Absence of suitable HLA matched or mismatched donor 6. Weight <6 kg 7. Presence of donor-specific anti-HLA antibodies directed against BE-CAR7 8. GvHD requiring systemic therapy 9. Systemic steroid therapy prednisolone >0.5 mg/kg/day 10. Known hypersensitivity to any of the test materials or related compounds 11. Active bacterial, fungal or viral infection not controlled by standard of care anti-microbial or anti-viral treatment. Uncontrolled bacteraemia/ fungaemia is defined as the ongoing detection of bacteria/fungus on blood cultures despite antibiotic or antifungal therapy. Uncontrolled viraemia is defined as rising viral loads on two consecutive occasions despite antiviral therapy. 12. Risk of pregnancy or non-compliance with contraception (if applicable). Girls of childbearing potential must have been tested negative in a pregnancy test within 14 days prior to inclusion. 13. Lactating female participants unwilling to stop breastfeeding 14. Prior CAR therapy known to be associated with ≥Grade 3 cytokine release syndrome (CRS) or ≥Grade 3 drug-related CNS toxicity |
| Date of first enrolment | 01/04/2022 |
| Date of final enrolment | 31/05/2027 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centres
London
WC1N 3JH
England
London
SE5 9RS
England
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Published as a supplement to the results publication |
| IPD sharing plan | The datasets generated and/or analysed during the current study will be published as a supplement to the results publication. The trial will comply with the Data Protection Act. If the patient, parents/guardians consent, anonymised data may be used for research and development including under commercial agreements reached by the hospital. The people who analyse the information will not be able to identify the subject and will not be able to find out the name, NHS number or contact details. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 08/12/2025 | 30/12/2025 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Interim results article | 14/06/2023 | 15/06/2023 | Yes | No |
Editorial Notes
09/01/2026: The public and scientific contacts were updated.
30/12/2025: Publication reference and total final enrolment added.
28/05/2025: The recruitment end date was changed from 31/05/2025 to 31/05/2027.
23/05/2025: The following changes were made to the study record:
1. The inclusion criteria were updated.
2. The overall study end date was changed from 31/05/2026 to 31/05/2028.
3. The intention to publish date was changed from 30/09/2025 to 30/09/2029.
4. King's College Hospital was added to the study participating centre.
11/09/2024: The following changes have been made:
1. The recruitment end date was changed from 30/09/2024 to 31/05/2025.
2. A study contact was updated.
17/04/2024: The recruitment end date was changed from 01/04/2024 to 30/09/2024.
16/04/2024: The following changes were made to the trial record:
1. The overall end date was changed from 30/09/2024 to 31/05/2026.
2. The ethics approval was added.
3. The clincaltrials.gov number was added.
15/06/2023: Publication reference added.
06/04/2022: ISRCTN received notification of combined HRA/MHRA approval for this trial on 05/04/2022.
11/01/2022: Trial's existence confirmed by the HRA.
