Goldilocks - determining if personalised drug monitoring of fludarabine in children and young adults with acute lymphoblastic leukaemia who are undergoing CAR-T therapy is feasible and can improve outcome whilst minimising toxicity

Plain English summary of protocol

Background and study aims
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.

Who can participate?
Patients less than 25 years old receiving fludarabine and cyclophosphamide as lymphodepletion before CD19 CAR T-cell therapy

What does the study involve?
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.

What are the possible benefits and risks of participating?
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. The benefit of this study for the individual suffering from life-threatening r/r B-ALL is the potential for a cure by optimizing CAR T outcomes. The median overall survival has been reported as 7.5 months in paediatric patients with r/r ALL. In addition, affected patients often report poor general and mental health and functional impairment. Children and young people with B-ALL experience a range of debilitating symptoms including fatigue feeling weak or breathless, bony pain, fevers, easy bruising/bleeding, headaches and visual loss. It also significantly affects the ability of both the patient and their caregivers to do daily tasks and maintain employment or education. While tisagenlecleucel has changed the treatment landscape for r/r B ALL, the outcome of patients with treatment failure is dismal. Real-time monitoring has the potential to reduce treatment failure associated with fludarabine underexposure (< 14mg/L.h) and toxicities associated with overexposure. Patients treated at centres within the UK will obtain an immediate benefit from this study.
Additional blood sampling is unlikely to cause inconvenience to the participant as they will have a central line and already be an inpatient in the hospital due to undergoing the lymphodepletion prior to their CAR-T treatment. Samples for fludarabine monitoring will be taken at the same time as clinical samples where possible.
Discussion of the trial with the participants and their families may cause distress at what is already a very difficult time for them. It is felt that this would be minimal as the potential benefits of the trial far outweigh the risks.
There is also a risk of breach of confidentiality. For the trial patient personal data is pseudo anonymised with the patients date of birth the only information recorded on patient registration forms. Following registration, patients are allocated a unique study number (study ID number), a copy of which will be sent to the relevant site for their records. All further communication regarding the patient, and clinical information collected on the patient will use the study ID number only. Data will be retained at the Newcastle Cancer Centre Pharmacology Group (NCCPG) and will be subject to the Data Protection Act 2018.

Where is the study run from?
Newcastle upon Tyne Hospitals NHS Foundation Trust (UK)

When is the study starting and how long is it expected to run for?
September 2025 to September 2028

Who is funding the study?
The Little Princess Trust (UK)

Who is the main contact?
1. Dr Shelby Barnett, shelby.barnett@nhs.net
2. Dr Geoff Shenton, geoff.shenton1@nhs.net

Plain English summary under review with external organisation

Contact information

Study information

Eligibility

Locations

Countries of recruitment

• England
• United Kingdom

Study participating centres

Sponsor information

Newcastle upon Tyne Hospitals NHS Foundation Trust
Hospital/treatment centre

Newcastle Joint Research Office
Level 1. Regent Point
Regent Farm Road
Gosforth
Newcastle upon Tyne
NE3 3HD
England
United Kingdom

Phone	+44 (0)191 28 26774
Email	laura.loraine@nhs.net
Website	http://www.newcastle-hospitals.org.uk/
"ROR"	https://ror.org/05p40t847

Funders

Funder type

Charity

Results and Publications

Editorial Notes

22/09/2025: Study's existence confirmed by the HRA.