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

NCT05397184 | Unknown Phase 1 DMC

• 1 other identifier: 19IC17
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Relapsed/Refractory T-cell Acute Lymphoid Leukaemia

Outcome Measures

Primary Outcomes (1)

• 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.

  1 year

Secondary Outcomes (1)

• Number of patients achieving disease remission ahead of allo-SCT

  28 days

Study Arms (1)

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.

Biological: Cryopreserved BE CAR7 T cells (BE752TBCCLCAR7PBL)

Interventions

Cryopreserved BE CAR7 T cells (BE752TBCCLCAR7PBL) 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

Also known as: BECAR7

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

Eligibility Criteria

• Age: 6 Months - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may not qualify if:

• 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
• 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.
• 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

Sponsors & Collaborators

• Great Ormond Street Hospital for Children NHS Foundation Trust: lead
• UCL Great Ormond Street Institute of Child Health: collaborator
• Medical Research Council: collaborator

Study Sites (1)

Ilyas Ali

London, WC1N 1EH, United Kingdom

RECRUITING

MeSH Terms

Conditions

Recurrence

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Waseem Qasim, Professor

  Great Ormond Street Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Robert Chiesa, Dr

CONTACT

020 7405 9200; Robert.Chiesa@gosh.nhs.uk

Agnieszka B Kubat, MSc

CONTACT

07502269573; a.kubat@ucl.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Not applicable (Open Label)
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase 1, open label, non randomised

Study Record Dates

• First Submitted: May 13, 2022
• First Posted: May 31, 2022
• Study Start: April 19, 2022
• Primary Completion: April 1, 2024
• Study Completion: February 28, 2025
• Last Updated: July 5, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)