Base Edited CAR7 T Cells to Treat T Cell Malignancies (TvT CAR7)

NCT ID: NCT05397184

Last Updated: 2023-07-05

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-19
• Study Completion Date: 2025-02-28

Brief 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). 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.

Conditions

Relapsed/Refractory T-cell Acute Lymphoid Leukaemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Single-dose intravenous infusion of a banded dose of CAR7+ T cells/kg BECAR7

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.

Group Type: EXPERIMENTAL

Cryopreserved BE CAR7 T cells (BE752TBCCLCAR7PBL)

Intervention Type: BIOLOGICAL

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

Interventions

Cryopreserved BE CAR7 T cells (BE752TBCCLCAR7PBL)

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

Intervention Type: BIOLOGICAL

Other Intervention Names

BECAR7

Eligibility Criteria

Inclusion Criteria

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

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

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

UCL Great Ormond Street Institute of Child Health

OTHER

Sponsor Role: collaborator

Medical Research Council

OTHER_GOV

Sponsor Role: collaborator

Great Ormond Street Hospital for Children NHS Foundation Trust

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Waseem Qasim, Professor

Role: PRINCIPAL_INVESTIGATOR

Great Ormond Street Hospital

Locations

Ilyas Ali

London, , United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

Robert Chiesa, Dr

Role: CONTACT

Robert.Chiesa@gosh.nhs.uk

020 7405 9200 ext. 8434

Agnieszka B Kubat, MSc

Role: CONTACT

a.kubat@ucl.ac.uk

07502269573

Facility Contacts

Ilyas Ali, MSc

Role: primary

Ilyas.Ali@gosh.nhs.uk

+44 (0)207 905 2863

Vanshree Patel, Dr

Role: backup

Vanshree.Patel@gosh.nhs.uk

+44 (0)207 905 2863

Other Identifiers

19IC17

Identifier Type: -

Identifier Source: org_study_id