Trial Details
Trial status:
Active (recruiting)
Recruitment start date:
10/11/2025
Funder:
Medical Research Council (MRC) & Great Ormond Street Hospital Children’s Charity (GOSHCC)
Sponsor:
UCL
Chief Investigator:
CI: Dr Paul Maciocia; Paediatric Clinical Lead: Dr Sara Ghorashian
Recruitment target:
12 Adults and 12 Paediatric (<18 years) participants
EudraCT number:
2022-003497-23
Contact details:
ctc.FRACTALL@ucl.ac.uk
Note: For enquiries only. DO NOT use for clinical referrals.
Lay summary:
FRACTALL
Fratricide-Resistant Autologous Chimeric Antigen Receptor T cells targeting CCR9 for the treatment of T cell Acute Lymphoblastic Leukaemia/ Lymphoma
Description
Design: Multi-centre, non-randomised, open-label Phase I clinical trial evaluating safety of novel autologous CARCCR9 T cells for patients with high-risk, relapsed/refractory (r/r) T-ALL/T-LBL. 
Treatment:
CARCCR9 T cells (a CAR-T cell therapy targeting the CCR9 receptor).

Leukapheresis: following registration, patients will undergo an unstimulated leukapheresis which will be sent to ‘Cell & Vector Innovation Centre’ (CVIC) at the Royal Free Hospital for manufacture of the autologous CAR T cells.

Lymphodepletion: prior to CAR T cell infusion, patients will receive cyclophosphamide 500 mg/m2 on Days -6 and -5 (2 doses) and fludarabine 30 mg/m2 on Days -6 to -3 (4 doses).

CAR T cell administration: a single infusion of CAR T cells will be administered intravenously on Day 0.

Key inclusion/exclusion criteria:
Key inclusion criteria:
1. Relapsed or refractory T-ALL/ T-LBL following at least:
         • Patients ≥18 years old: 1 standard prior line of combination cytotoxic therapy
         • Patients
2. CCR9-positive disease as assessed by flow cytometry. 
3. T-LBL patients only: Patients must have measurable disease which is CCR9-positive by standard flow cytometry tests (on tissue biopsy, blood, bone marrow, or malignant effusion). 
4. Agreement to have a pregnancy test, use adequate contraception (if applicable)
5. Written informed consent

Key exclusion criteria:
1. ECOG performance score > 2 (patients aged ≥10 years old) OR Lanksy score ≤50% (patients aged
2. Stem Cell Transplant patients only: active significant acute GvHD (overall Grade ≥ II, modified Glucksberg criteria) or moderate/severe chronic GvHD (NIH consensus criteria) requiring immunosuppressive therapy and/or systemic steroids
3. Active CNS involvement of disease
4. Pre-existing neurological disorders unrelated to the malignancy, including, but not limited to, epilepsy, dementia, Parkinson’s disease, cerebellar disease, severe brain injuries, dementia, uncontrolled mental illness, and psychosis.
5. Active hepatitis B, C or HIV infection
6. Oxygen saturation ≤ 90% on air
7. Bilirubin >3 x upper limit of normal
8. GFR
9. Cardiac dysfunction as defined by:
        • Patients ≥18 years old: 
            - cardiac dysrhythmias (excluding well-controlled atrial fibrillation or other supraventricular tachycardia) or
            - significant cardiac disease (any of the following within six months prior to screening: myocardial infarction, unstable angina, stroke, and coronary bypass surgery) or 
            - left ventricular ejection fraction
        • Patients
10. Active or significant gastrointestinal (GI) disorders (e.g. inflammatory bowel disease, recent bowel surgery).
11. Active autoimmune disease.
12. Receipt of any vaccination (including live attenuated vaccines) within 6 weeks prior to lymphodepletion.
13. Patients receiving corticosteroids at a supraphysiological dose that cannot be discontinued
14. Known allergy to albumin, DMSO, PBS/EDTA (or any component of the ATIMP)
15. Any contraindications to lymphodepletion or to the use of cyclophosphamide or fludarabine as per local SmPC
16. Women who are pregnant or breast feeding
17. Life expectancy
18. Fulminant or rapidly progressive disease
Duration of recruitment: 2 years
Aim
1. To determine the safety of CARCCR9 T cells 
2. To determine the feasibility of generating CARCCR9 T cells
3. To evaluate the potential efficacy of CARCCR9 T cells in patients with relapsed/refractory T-ALL/T-LBL
Trial protocols
Trial protocols must not be applied to patients treated outside trials. UCL CTC can only ensure that approved trial investigators are provided with amendments to protocols.
No protocols have been currently made available for download
Trial documents
No documents have been currently made available for download
Contact Us
Cancer Research UK & UCL Cancer Trials Centre
University College London
90 Tottenham Court Road
London
W1T 4TJ

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Email:
ctc.enquiries@ucl.ac.uk
Telephone:
+44 (0)20 7679 9898 (General CTC Enquiries)
University College London, Gower Street, London, WC1E 6BT +44 (0)20 7679 2000

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