NCT07499349 Establishment of a Phamacokinetik Model for Erwinase Pharmacokinetiks: The Aim of This Sub Study is to Optimize Target Trough Attainment While Minimizing High Exposures That Impose Increased Risk of Side Effects Such as Hyperammonemia
| NCT ID | NCT07499349 |
| Status | Recruiting |
| Phase | — |
| Sponsor | Aarhus University Hospital |
| Condition | Acute Lymphoblastic Leukemia |
| Study Type | OBSERVATIONAL |
| Enrollment | 475 participants |
| Start Date | 2008-07-01 |
| Primary Completion | 2026-06-30 |
Eligibility & Interventions
Eligibility Fast-Check
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What to Expect as a Participant
This is an observational study. You will not receive an experimental treatment; researchers will collect data based on your existing condition or standard treatment.
This trial targets 475 participants in total. It began in 2008-07-01 with a primary completion date of 2026-06-30.
⚠ This information is for research awareness only. Always consult your physician before joining any clinical trial. Participation is voluntary and you may withdraw at any time.
Brief Summary
The aim of this study is to optimize target trough attainment while minimizing high exposures that impose increased risk of side effects such as hyperammonemia. Clinical pharmacology is based on the principle that plasma drug concentrations are linked to therapeutic effects. Therefore, understanding plasma drug concentrations is critical to balancing efficacy and toxicity in oncology treatment, as shown with Erwinase where elevated activity increases the risk of hyperammonemia. TDM can guide dose adjustments to reduce PK variability and improve outcomes. However, harnessing all information from TDM data can be challenging due to sparse and uneven sampling, and multiple sources of PK variability. Advanced analytical tools, such as pharmacometrics and population PK modelling, can address these complexities by quantifying exposure variability in patients and linking it to dosage, patient characteristics, and biomarkers. Methods: This is a NOPHO study. Within the NOPHO, Erwinase was administered intramuscularly (IM) at a dose of 20,000 IU/m² on a Mon-Wed-Fri schedule for two weeks. All non-high-risk (non-HR) patients received the same dose. HR-patients received additional Erwinase, with three doses at 2-day intervals in each treatment block. Activity levels are available from \~150 patients; among these, 20 patients received more than six doses (range: 7-42). In the A2G-1, Erwinase was administered intravenously (IV) at 20,000 IU/m², substituting one PEG-asparaginase dose with seven Erwinase doses every other day. The number of doses received varied depending on the timing of hypersensitivity reactions. Activity levels are already available from \>90 patients. Measurement of Erwinase enzyme activity levels is performed at the Asparaginase Lab in Aarhus. All samples have been analysed. The data will undergo further cleaning, validation, followed by integration with patient characteristics in a population PK model. Data Management and Security in Uppsala: All PK data will be pseudo-anonymized before being securely transferred to Uppsala University through the Allvis data portal. Data handling and formatting will be scripted in R to ensure transparency and reproducibility. Modelling will be performed on the UPPMAX computing cluster via the Swedish National Academic Infrastructure for Supercomputing. Workflow, statistics and perspectives: The modelling workflow will be performed as follows: 1. A PK model for Erwinase will be established based on asparaginase enzyme activity TDM data obtained from Nordic/Baltic ALL patients treated under the NOPHO and A2G-1. Drug clearance, volume of distribution, absorption, and bioavailability will be derived to describe the PK of both routes of Erwinase administration (IV vs IM). Nonlinear mixed-effects modelling will be applied to obtain both typical population PK parameters as well as patient variability parameters. Potential changes in parameters within patients over time will also be explored. Model development and evaluation will be conducted using NONMEM17. Model selection will be based on statistical fit and biological plausibility. Goodness of fit plots and visual predictive checks will ensure the PK model adequately describes the observed data. 2. The Erwinase PK model will be applied to explore alternative dosing strategies, as simultaneously achieving aimed target attainment (≥100 IU/L).
Eligibility Criteria
Inclusion Criteria: * ALL treated with Erwinase Exclusion Criteria: * not treated with Erwinase
Contact & Investigator
Shiva Leisner, MD
PRINCIPAL INVESTIGATOR
Aarhus University Hospital
Frequently Asked Questions
Who can join the NCT07499349 clinical trial?
This trial is open to participants of all sexes, aged 1 Month or older, up to 45 Years, studying Acute Lymphoblastic Leukemia. Full inclusion and exclusion criteria are listed in the Eligibility Criteria section. Always confirm your eligibility with the research team before applying.
Is NCT07499349 currently recruiting?
Yes, NCT07499349 is actively recruiting participants. Contact the research team at shiva.leisner@clin.au.dk for enrollment information.
Where is the NCT07499349 trial being conducted?
This trial is being conducted at Aarhus, Denmark.
Who is sponsoring the NCT07499349 clinical trial?
NCT07499349 is sponsored by Aarhus University Hospital. The principal investigator is Shiva Leisner, MD at Aarhus University Hospital. The trial plans to enroll 475 participants.
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