Relapsed/Refractory T-cell Acute Lymphoid LeukaemiaPhase 1TvT CAR7NCT05397184
Base Edited CAR7 T Cells to Treat T Cell Malignancies (TvT CAR7)
A Phase 1 study testing Cryopreserved BE CAR7 T cells (BE752TBCCLCAR7PBL) in people with Relapsed/Refractory T-cell Acute Lymphoid Leukaemia, run by Great Ormond Street Hospital for Children NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 6 months to 16 years
- Conditions the study is for
- Relapsed/Refractory T-cell Acute Lymphoid Leukaemia
- What is being tested?
- Cryopreserved BE CAR7 T cells (BE752TBCCLCAR7PBL)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 19 Apr 2022to 28 Feb 2025
- 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 6 months to 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
None listed.
Who cannot join
- Patients/parents unwilling to undergo a follow-up for 15 years
- Foreseeable poor compliance to the study procedures
- Evidence of disease progression after cytoreduction
- Uncontrollable CNS leukaemia or neurological symptoms defined as CNS grade 3 (per National Comprehensive Cancer Network guidelines)
- Absence of suitable HLA matched or mismatched donor
- Weight <6 kg
Show all 14Show fewer
- Presence of donor-specific anti-HLA antibodies directed against BE-CAR7
- GvHD requiring systemic therapy
- Systemic steroid therapy prednisolone >0.5 mg/kg/day
- Known hypersensitivity to any of the test materials or related compounds
- 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.
- 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.
- Lactating female participants unwilling to stop breastfeeding
- Prior CAR therapy known to be associated with ≥Grade 3 cytokine release syndrome (CRS) or ≥Grade 3 drug-related CNS toxicity
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Ilyas Ali
London, WC1N 1EH
Ilyas Ali, MSc, +44 (0)207 905 2863, Ilyas.Ali@gosh.nhs.uk
Vanshree Patel, Dr, +44 (0)207 905 2863, Vanshree.Patel@gosh.nhs.uk
About this study
Official title: Phase 1 Study of Base Edited CAR7 T Cells to Treat T Cell Malignancies (TvT CAR7)
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 them 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.
Read the detailed description
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.
- Being tested
- Cryopreserved BE CAR7 T cells (BE752TBCCLCAR7PBL)
- Medical subject headings
- Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cryopreserved BE CAR7 T cells (BE752TBCCLCAR7PBL)Biological
Also called BECAR7
Single-dose intravenous infusion (weight-based dosing) of a banded dose of CAR7+ T cells/kg BECAR7 Total duration of treatment: 28 days Follow-up: 12 months
| Study group | Role | What they receive |
|---|---|---|
| Single-dose intravenous infusion of a banded dose of CAR7+ T cells/kg BECAR7 | Experimental | Single-dose intravenous infusion (weight-based dosing) of CAR7+ T cells/kg BECAR7 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. 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. Receives: Biological: Cryopreserved BE CAR7 T cells (BE752TBCCLCAR7PBL) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency and description of adverse events after BE-CAR7 infusion
Incidence of Grade 3-5 toxicities occurring from infusion up to one year follow-up.
Severe Adverse Reactions of special interest will be CRS, ICANS and GvHD. American Society of Bone Marrow Transplantation grading scales for CRS/ICANS and National Institute of Health criteria for GVHD will be applied. Commo Terminology Criteria nomenclature will be used to grade other adverse events.
Measured: 1 year
Secondary outcomes (1)
Number of patients achieving disease remission ahead of allo-SCT
Remission rate will be assessed by bone marrow and CNS evaluation after 28 days. 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.
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2022
- Study start19 Apr 2022
- Primary completion1 Apr 2024 (estimated)
- Study completion28 Feb 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed/Refractory T-cell Acute Lymphoid LeukaemiaStudies 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
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Phase 1, open label, non randomised
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Great Ormond Street Hospital for Children NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- UCL Great Ormond Street Institute of Child Health, Medical Research Council
- Responsible party
- Sponsor
- Investigators
- Waseem Qasim, Professor, Principal investigator, Great Ormond Street Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05397184
- Sponsor's protocol ID
- 19IC17
- Acronym
- TvT CAR7
- Status last verified
- Jun 2023
- First submitted
- 13 May 2022
- Last updated
- 5 Jul 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of Base Edited CAR7 T Cells to Treat T Cell Malignancies (TvT CAR7)
- ClinicalTrials.gov ID
- NCT05397184
- Acronym / sponsor ID
- TvT CAR7 / 19IC17
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Great Ormond Street Hospital for Children NHS Foundation TrustUniversity, hospital or other
- Collaborators
- UCL Great Ormond Street Institute of Child Health, Medical Research Council
- Study start
- 19 Apr 2022 (actual)
- Primary completion
- 1 Apr 2024 (estimated)
- Study completion
- 28 Feb 2025 (estimated)
- First posted
- 31 May 2022 (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.
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 them 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.
Detailed description
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.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Phase 1, open label, non randomised
| Arm | Type | Receives |
|---|---|---|
| Single-dose intravenous infusion of a banded dose of CAR7+ T cells/kg BECAR7 | Experimental | Biological: Cryopreserved BE CAR7 T cells (BE752TBCCLCAR7PBL)Single-dose intravenous infusion (weight-based dosing) of CAR7+ T cells/kg BECAR7 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. 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. |
Who may qualify
- Ages
- 6 months to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (0 listed)
Key exclusion criteria (14 listed)
- Patients/parents unwilling to undergo a follow-up for 15 years
- Foreseeable poor compliance to the study procedures
- Evidence of disease progression after cytoreduction
- Uncontrollable CNS leukaemia or neurological symptoms defined as CNS grade 3 (per National Comprehensive Cancer Network guidelines)
- Absence of suitable HLA matched or mismatched donor
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 |
|---|---|---|
| Cryopreserved BE CAR7 T cells (BE752TBCCLCAR7PBL)Also: BECAR7Single-dose intravenous infusion (weight-based dosing) of a banded dose of CAR7+ T cells/kg BECAR7 Total duration of treatment: 28 days Follow-up: 12 months | Biological | Single-dose intravenous infusion of a banded dose of CAR7+ T cells/kg BECAR7 |
Primary outcome
Frequency and description of adverse events after BE-CAR7 infusion
Time frame: 1 year
Incidence of Grade 3-5 toxicities occurring from infusion up to one year follow-up. Severe Adverse Reactions of special interest will be CRS, ICANS and GvHD. American Society of Bone Marrow Transplantation grading scales for CRS/ICANS and National Institute of Health criteria for GVHD will be applied. Commo Terminology Criteria nomenclature will be used to grade other adverse events.
1 secondary outcome
Number of patients achieving disease remission ahead of allo-SCT
Time frame: 28 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2023.
- Individual participant dataSharing planned: No
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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.
Waseem Qasim, Professor principal investigator
Great Ormond Street Hospital
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 Cryopreserved BE CAR7 T cells (BE752TBCCLCAR7PBL) in people with Relapsed/Refractory T-cell Acute Lymphoid Leukaemia, run by Great Ormond Street Hospital for Children NHS Foundation Trust 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 0 inclusion and 14 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: status not confirmed, as of the sponsor's last update on 5 Jul 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Robert Chiesa, Dr (020 7405 9200 ext. 8434, Robert.Chiesa@gosh.nhs.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency and description of adverse events after BE-CAR7 infusion (time frame: 1 year). 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 5 Jul 2023.