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

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

Status

Active, not recruiting

Phases

Phase 4

Study type

Interventional

Source

ISRCTN

Registry ID

ISRCTN10473740

Enrollment

Registered

2025-10-30

Start date

2026-02-01

Completion date

Unknown

Last updated

2026-01-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Acute lymphoblastic leukaemia Cancer

Interventions

A single-arm trial including real-time therapeutic drug monitoring of fludarabine to ensure all patients achieve a target cumulative exposure of 16-20mg/L.h during the lymphodepletion regimen. Observa

Eligibility

Sex/Gender

All

Age

28 Days to 25 Years

Inclusion criteria

Inclusion criteria: 1. Age >28 days and <25 years old 2. Receiving fludarabine (30 mg/m2/day for 4 days) & cyclophosphamide (500 mg/m2/day for 2 days) as lymphodepletion prior to CD19 CAR T-cell therapy* 3. Capacity for the patient or the patient’s guardian/ legal representative to provide written informed consent *This indicates the standard lymphodepletion regimen, dose modifications from this standard regimen for renal impairment and young age do not impact the eligibility for inclusion

Exclusion criteria

Exclusion criteria: 1. Contraindications which would prevent fludarabine or cyclophosphamide being used as lymphodepletion agents 2. Pregnancy or breastfeeding in patients 3. Inclusion in other interventional CAR T trials

Design outcomes

Primary

Measure	Time frame
Feasibility of implementation is measured by the proportion of enrolled patients in whom real-time PK-guided fludarabine monitoring and dose adjustments have been successfully implemented at the close of the study	—

Secondary

Measure	Time frame
Secondary and exploratory: Benefit of implementation is measured by assessing the impact of fludarabine and cyclophosphamide exposure on patient outcomes compared to a historical cohort with no dose intervention at 1 year following CAR T cell infusion: 1. Overall survival (OS) 2. Event-free survival (EFS) 3. Leukaemia-free survival (LFS) (*Stringent EFS) 4. Cumulative incidence of relapse 5. Cumulative incidence of loss of B cell aplasia 6. Cumulative incidence of cytokine relapse syndrome (CRS) 7. Cumulative incidence of grade 3-4 immune effector cell-associated neurotoxicity syndrome (ICANS) 8. The associated haematological toxicity Mechanistic: The impact of fludarabine exposure and cytokine profile at 0, +7 and +14 days will be measured by patient outcomes (as above) at 1 year following CAR T cell infusion	—

Measure

Time frame

Secondary and exploratory: Benefit of implementation is measured by assessing the impact of fludarabine and cyclophosphamide exposure on patient outcomes compared to a historical cohort with no dose intervention at 1 year following CAR T cell infusion: 1. Overall survival (OS) 2. Event-free survival (EFS) 3. Leukaemia-free survival (LFS) (*Stringent EFS) 4. Cumulative incidence of relapse 5. Cumulative incidence of loss of B cell aplasia 6. Cumulative incidence of cytokine relapse syndrome (CRS) 7. Cumulative incidence of grade 3-4 immune effector cell-associated neurotoxicity syndrome (ICANS) 8. The associated haematological toxicity Mechanistic: The impact of fludarabine exposure and cytokine profile at 0, +7 and +14 days will be measured by patient outcomes (as above) at 1 year following CAR T cell infusion

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Countries

England, United Kingdom

Outcome results

None listed

Source: ISRCTN (via WHO ICTRP) · Data processed: Feb 4, 2026