Relapsed or refractory T-cell malignancies (T-ALL or T-LBL) Cancer
Conditions
Interventions
Both cohorts (adult (=18 years old) and paediatric:
1. Leukapheresis: following registration, patients will undergo an unstimulated leukapheresis which will be used for the manufacture of the CARCCR9
Sponsors
University College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Relapsed or refractory T-ALL/T-LBL following at least: 1.1. Patients =18 years old: one standard prior line of combination cytotoxic therapy 1.2. Patients <18 years old: two standard prior lines of combination cytotoxic therapy 2. All disease types: 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
Exclusion criteria
Exclusion criteria: 1. ECOG performance score >2 (patients aged =10 years old) OR Lanksy score =50% (patients aged 3 x upper limit of normal 7. GFR <30 ml/min 8. Cardiac dysfunction as defined by: 8.1. Patients =18 years old: cardiac dysrhythmias (excluding well-controlled atrial fibrillation or other supraventricular tachycardia) or significant cardiac disease and left ventricular ejection fraction <40% 8.2. Patients <18 years old: Left ventricle shortening fraction <28% on echocardiogram 9. Patients receiving corticosteroids at a supraphysiological dose that cannot be discontinued 10. Known allergy to albumin, DMSO, PBS/EDTA (or any component of the ATIMP) 11. Any contraindications to lymphodepletion or to the use of cyclophosphamide or fludarabine as per local SmPC 12. Women who are pregnant or breastfeeding 13. Life expectancy <3 months 14. Fulminant or rapidly progressive disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Feasibility of generation of CARCCR9 T cells as evaluated by the number of therapeutic products generated. 2. Toxicity following CARCCR9 T cell administration as evaluated by the incidence of grade 3-5 toxicity causally related to the ATIMP occurring within 28 days of CAR T cell infusion. | — |
Secondary
| Measure | Time frame |
|---|---|
| Measured up to 2 years (unless noted otherwise): 1. Proportion of responders and depth of response over 12 months post-ATIMP infusion 2. Persistence and frequency of circulating CARCCR9 T cells in peripheral blood as assessed by flow cytometry and qPCR 3. Time to Disease Progression 4. Event-free survival at 1 and 2 years after immunotherapy with CARCCR9 T cells 5. Overall survival at 1 and 2 years after immunotherapy with CARCCR9 T cells 6. Quality of life of participants post CARCCR9 T cells assessed by the EORTC QLQ-C30 questionnaire Exploratory endpoints - measured up to 2 years (unless noted otherwise): 1. Expansion and persistence of CARCCR9 T cells in bone marrow (BM) +/- cerebrospinal fluid (CSF), as assessed by immunophenotyping and qPCR 2. Cytokine response analysis up to day 28 post CARCCR9 T cells infusion 3. Analysis of peripheral blood T and NK cell number and function in patients up to 2 years post CARCCR9 T cells infusion | — |
Countries
United Kingdom
Contacts
Public ContactFRACTALL Trial Manager
Outcome results
None listed