CAR T cells to fight T cell leukaemia
| ISRCTN | ISRCTN15323014 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN15323014 |
| EudraCT/CTIS number | 2021-004312-25 |
| IRAS number | 1004379 |
| ClinicalTrials.gov number | NCT05397184 |
| Secondary identifying numbers | 19IC17, IRAS 1004379 |
- Submission date
- 11/01/2022
- Registration date
- 06/04/2022
- Last edited
- 11/09/2024
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Plain English Summary
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 children aged 6 months up to 16 years 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 to 16 years 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 September 2024
Who is funding the study?
Medical Research Council (MRC) (UK)
Who is the main contact?
1. Prof. Waseem Qasim, Waseem.Qasim@gosh.nhs.uk
2. Agnieszka Kubat, Agnieszka.Kubat@gosh.nhs.uk
Plain English summary under review with external organization
Contact information
Principal Investigator
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
30 Guilford Street
London
WC1N 1EH
United Kingdom
| hannah.badham@gosh.nhs.uk |
Scientific
Clinical Project Manager
Infection, Immunity and Inflammation Research & Teaching Department
Molecular and Cellular Immunology Section
UCL Great Ormond Street Institute of Child Health
30 Guilford Street
London
WC1N 1EH
United Kingdom
| Phone | +44 (0)203 978 3770 |
|---|---|
| a.kubat@ucl.ac.uk |
Study information
| Study design | Single-arm non-randomized study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | Phase I study of base edited CAR7 T cells to treat T cell malignancies (TvT CAR7) |
| Study acronym | TvT CAR7 |
| Study hypothesis | The primary objective is to assess the safety of base edited (BE)-CAR7s in paediatric 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 |
| Condition | 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | BE-CAR7 |
| Primary outcome measure | The safety of BE-CAR7s in paediatric 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: 1. Clinical examination and vital signs 2. Standard blood parameters 3. Oxygen saturation and cardiac assessment 4. Cytokines 5. Infections National Cancer Institute Common Terminology Criteria for Adverse Event will be used to grade events. Specialized grading scales for cytokine release syndrome (CRS) and graft versus host disease (GVHD) will be applied. |
| Secondary outcome measures | 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. |
| Overall study start date | 04/01/2022 |
| Overall study end date | 31/05/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 6 Months |
| Upper age limit | 16 Years |
| Sex | Both |
| Target number of participants | 10 |
| Participant 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 |
| Participant 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 |
| Recruitment start date | 01/04/2022 |
| Recruitment end date | 31/05/2025 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
London
WC1N 3JH
United Kingdom
Sponsor information
Hospital/treatment centre
30 Guilford Street
London
WC1N 1EH
England
United Kingdom
| Phone | +44 (0)207 905 2863 |
|---|---|
| research.governance@gosh.nhs.uk | |
| Website | http://www.gosh.nhs.uk/ |
"ROR" |
https://ror.org/00zn2c847 |
Funders
Funder type
Research council
Government organisation / National government
- Alternative name(s)
- Medical Research Council (United Kingdom), UK Medical Research Council, MRC
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 30/09/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Published as a supplement to the results publication |
| Publication and dissemination plan | 1. Peer-reviewed scientific journals 2. Internal report 3. Conference presentation 4. Other publications 5. Protocol is not published yet. Protocol with redacted confidential information will be uploaded after study closeout. |
| 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? |
|---|---|---|---|---|---|
| Interim results article | 14/06/2023 | 15/06/2023 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
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.
