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Contact the study team using the details below to take part. If there are no contact details below please ask your doctor in the first instance.
Prof
WASEEM
QASIM
w.qasim@ucl.ac.uk
Kerry
Gilroy
kerry.gilroy@gosh.nhs.uk
Mrs
Agnieszka
Kubat
a.kubat@ucl.ac.uk
Batoul
Ahmed
batoul.ahmed@gosh.nhs.uk
Malignant neoplasms, stated or presumed to be primary, of lymphoid, haematopoietic and related tissue
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Novel strategies against T-ALL using chimeric antigen receptor (CAR) T cells are problematic because of issues such as fratricide of healthy T cells and the need to reconstitute protective T cell immunity. Suitable antigens for targeting T cell malignancies include CD3,TCRαβ,CD5 and CD7. The latter has recently exhibited promise in trials where T cells were disrupted for CD7 to allow expression of anti-CD7 CAR (CAR7). Strategies for disruption include protein based inhibition of CD7,and genomic disruption using CRISPR/Cas9.
We have developed a next generation base-editing approach which uses CRISPR guided cytidine deamination to create premature stop codons or splice site disruption through highly precise C>T base conversions. The technology has translated remarkably well to a GMP phase,and we are funded by Wellcome Trust (WT) to generate banks of ‘universal’ healthy donor T cells for Phase 1 trials in paediatric Acute Myeloid Leukaemia. Base-edited (BE) CAR T cells targeting either CD33,CD123 or CD7 are being generated,and the latter could have immediate impact against T-ALL. Our preclinical 'TvT' modelling has found BE-CAR7 cells are highly effective in vitro and in humanised models of T cell leukaemia. BE-CAR7 T cells express CAR7,but are devoid of CD7,endogenous TCRab (thus non-alloreactive) and CD52 (evade serotherapy). The application of base-editing rather than existing Cas9 which causes DNA breaks,has notable advantages in terms of eliminating translocations that otherwise arise during multiplexed genome editing.We propose an accelerated route to therapy for children with r/r T-ALL by drawing on BE-CAR7 cell banks with permission of WT. A TvT Phase 1 trial will aim to secure remission ahead of programmed allo-SCT and will generate important safety data. Children with r/r T-ALL will undergo lymphodepletion and receive a single dose of BE-CAR7 and if remission is secured within 28 days,will proceed to bone marrow transplantation and 12m follow-up.
Start dates may differ between countries and research sites. The research team are responsible for keeping the information up-to-date.
The recruitment start and end dates are as follows:
Interventional type: Gene Therapy;
You can take part if:
You may not be able to take part 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,see Appendix E). • Absence of suitable HLA matched or mismatched donor • Weight <6 kgs • Presence of donor-specific anti-HLA antibodies directed against BE-CAR7 • GvHD requiring systemic therapy • Systemic steroid therapy prednisolone >0.5mg/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 anti-fungal 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
Below are the locations for where you can take part in the trial. Please note that not all sites may be open.
Kerry
Gilroy
kerry.gilroy@gosh.nhs.uk
Mrs
Agnieszka
Kubat
a.kubat@ucl.ac.uk
Prof
WASEEM
QASIM
w.qasim@ucl.ac.uk
Batoul
Ahmed
batoul.ahmed@gosh.nhs.uk
The study is sponsored by GREAT ORMOND STREET HOSPITAL FOR CHILDREN NHS FOUNDATION TRUST and funded by Medical Research Council (MRC) .
Your feedback is important to us. It will help us improve the quality of the study information on this site. Please answer both questions.
Read full details
for Trial ID: CPMS 54419
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