Dataset Information

Food-effect study of nilotinib in chronic myeloid leukaemia (NiFo study): Enabling dose reduction and relief of treatment burden.

ABSTRACT:

Objectives

Taking advantage of its food-dependent bioavailability, the present study investigated the effect of a reduced dose taken with real-life meals on the pharmacokinetics (PK) of nilotinib in chronic myeloid leukaemia (CML) patients.

Methods

Nilotinib was taken fasted (300 mg BID, days 1-4) or with real-life meals (200 mg BID, days 5-11). Rich sampling (days 1, 3, 8, 11) allowed for non-compartmental PK analysis. Nilotinib exposure (AUC_0-12 h -C_min -C_max ) and its intra- and interpatient variability were compared between the two regimens. Adverse events were recorded by means of a patient diary and ECG monitoring.

Results

Fifteen patients aged 40-74 years participated. Nilotinib PK following 200 mg BID taken with a meal strongly resembled that of 300 mg BID taken fasted (C_min percentile (P)10-P90: 665-1404 ng/mL and 557-1743 ng/mL, respectively). Meals delayed nilotinib absorption. Intra- and interpatient variability were not increased by intake with meals. Nilotinib with food was well tolerated.

Conclusion

With support of therapeutic drug monitoring, the use of a reduced 200 mg nilotinib dose with real-life meals seems feasible and safe. Future (confirmatory) studies should further explore the usefulness of nilotinib dosing together with food, including the relationship with treatment efficacy as well as long-term effects on quality of life.

Clinical trial registration

NTR5000 (Netherlands Trial Register, www.trialregister.nl).

SUBMITTER: Boons CCLM

PROVIDER: S-EPMC7496780 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Publications

Food-effect study of nilotinib in chronic myeloid leukaemia (NiFo study): Enabling dose reduction and relief of treatment burden.

Boons Christel C L M CCLM den Hartog Yvonne M YM Janssen Jeroen J W M JJWM Zandvliet Anthe S AS Vos René M RM Swart Eleonora L EL Hendrikse N Harry NH Hugtenburg Jacqueline G JG

European journal of haematology 20200416 2

<h4>Objectives</h4>Taking advantage of its food-dependent bioavailability, the present study investigated the effect of a reduced dose taken with real-life meals on the pharmacokinetics (PK) of nilotinib in chronic myeloid leukaemia (CML) patients.<h4>Methods</h4>Nilotinib was taken fasted (300 mg BID, days 1-4) or with real-life meals (200 mg BID, days 5-11). Rich sampling (days 1, 3, 8, 11) allowed for non-compartmental PK analysis. Nilotinib exposure (AUC<sub>0-12 h</sub> -C<sub>min</sub> -C ...[more]

PMID: 32243653

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Project description:BackgroundDose reduction of tyrosine kinase inhibitors (TKI) in patients with chronic myeloid leukaemia (CML) with an optimal response to TKIs may support cost-effective medication use by maintaining therapeutic effectiveness while reducing adverse events and medication costs. As the choice for dose reduction depends on patients' individual needs and preferences, a patient-centred approach is warranted. Therefore, a study to evaluate the effectiveness of patient-guided dose reduction in patients with CML who are in a major or deep molecular response is designed.MethodsThis study is a prospective, multicentre, single-arm study. 147 patients with CML (aged ≥ 18 years) in chronic phase, who are treated with imatinib, bosutinib, dasatinib, nilotinib or ponatinib, and have reached at least major molecular response (defined as having BCR-ABL levels < 0.1% for an uninterrupted period of 6 months) are eligible. Patients will use an online patient decision aid and a shared decision making consultation will be held, after which patients who choose to will receive a personalised, lower TKI dose. Primary outcome is the proportion of patients with intervention failure at 12 months after dose reduction, defined as patients who have restarted their initial dose due to (expected) loss of major molecular response. For this, BCR-ABL1 levels will be analysed from blood samples drawn at baseline, 6 weeks after dose reduction and 3-monthly thereafter. Secondary outcomes include the proportion of patients with intervention failure at 6 and 18 months after dose reduction. Other outcomes include differences before and after dose reduction regarding the number and severity of patient-reported side effects; quality of life; beliefs about medicines; and medication adherence. Patients' level of decisional conflict and regret after choosing dose reduction will be assessed, as will the decisional process experienced by patients and healthcare providers.DiscussionOutcomes of this trial using a personalised approach will provide clinical and patient-reported data to guide future dose reduction of TKIs in CML. If the strategy appears to be effective, it may be implemented as another valid option to offer next to standard of care to prevent potential unnecessary exposure to higher TKI doses in this selected group of patients.Trial registrationEudraCT number 2021-006581-20.

Dataset Information

Food-effect study of nilotinib in chronic myeloid leukaemia (NiFo study): Enabling dose reduction and relief of treatment burden.

Objectives

Methods

Results

Conclusion

Clinical trial registration

Publications

Food-effect study of nilotinib in chronic myeloid leukaemia (NiFo study): Enabling dose reduction and relief of treatment burden.

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