Fludarabine Therapeutic Drug Monitoring in B-Cell ALL patients undergoing CAR-T-cell therapy
Research type
Research Study
Full title
Implementation of real-time fludarabine therapeutic drug monitoring analysis in the United Kingdom for relapsed/refractory B-cell acute lymphoblastic leukaemia patients undergoing chimeric antigen receptor (CAR) T-cell therapy
IRAS ID
1012095
Contact name
Shelby Barnett
Contact email
Sponsor organisation
Newcastle Upon Tyne Hospitals NHS Foundation Trust
ISRCTN Number
ISRCTN10473740
Research summary
Acute lymphoblastic leukaemia (ALL) is a type of blood cancer that primarily affects about 400 young people a year in the UK. For around 90% of these the outlook is positive, but 15-20% of these patients may experience a relapse. Relapsed ALL patients are challenging to treat, and each relapse typically leads to poorer outcomes.
One promising treatment for these difficult cases is CAR T-cell therapy. This therapy involves modifying the patient’s own immune cells (T-cells) in a lab so they can better target and fight the cancer. Before administering CAR T-cell therapy, it is necessary to deplete the patient’s normal T-cells. This is done by giving them chemotherapy drugs called fludarabine and cyclophosphamide in the week leading up to the therapy.
Recent research indicates that administering an optimal level of fludarabine can reduce the chance of relapse within a year after CAR T-cell therapy to less than 30%. In contrast, if fludarabine levels are too low, the likelihood of relapse jumps to at least double and in one study up to 100%. Unfortunately, around 40% of patients receiving CAR T-cell therapy have insufficient fludarabine levels.
To address this, we aim to personalise the dosing of fludarabine for CAR T-cell therapy patients in real time, ensuring they receive the optimal levels needed for effective treatment. We aim to recruit 50 patients (<25 years old) over three years from seven Children and Young Peoples CAR T hospitals in the UK. Blood samples taken on the first day will be sent to the Newcastle Cancer Centre Pharmacology Group (NCCPG) to measure fludarabine levels, allowing us to adjust doses for the following days to achieve optimal levels.
This research aims to enhance treatment outcomes by personalising fludarabine dosing and may help the NHS by reducing treatment failures, thus saving money and resources. This research is funded by The Little Princess Trust.REC name
North West - Liverpool Central Research Ethics Committee
REC reference
25/NW/0306
Date of REC Opinion
27 Oct 2025
REC opinion
Further Information Favourable Opinion