Acute myeloid Leukemia acute leukemia
Conditions
Interventions
This is a non-interventional study. Participants will receive venetoclax, hypomethylating agents (azacitidine or decitabine), and posaconazole as part of standard clinical care, at the discretion of t
Sponsors
Radboud Universitair Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: In order to be eligible to participate in this study, a patient must meet all of the following criteria:Adult patients (=18 years of age) with a confirmed diagnosis of AML according to the ELN 2022 criteriaPatients who are planned to receive, venetoclax in combination with a HMA (azacitidine or decitabine) Patients must be expected, based on clinical course and treating physician judgment, to have at least one period with posaconazole and one period without posaconazole during the first cycle of venetoclax therapyPatients must be able to ingest oral medication reliably and must not have ongoing gastrointestinal conditions (e.g., persistent vomiting) that, in the opinion of the investigator, would significantly impair oral drug absorption at the time of pharmacokinetic sampling.Written informed consent must be obtained from the patient prior to the performance of any study-specific procedures.
Exclusion criteria
Exclusion criteria: A potential participant who meets any of the following criteria will be excluded from participation in this study:Active invasive fungal infection on cycle 1 day 1 for which treatment with an azole is indicatedConcomitant treatment with medicinal products known to be strong or moderate inhibitors or inducers of CYP3A4, P-gp or UGT1a4, other than posaconazole, during pharmacokinetic sampling periods. As assessed with the KNMP “G-standaard”. Other interacting drugs are allowed as long as they do not interfere with venetoclax pharmacokinetics.Severe hepatic impairment, defined as Child–Pugh class C or AST or ALT >5 × the upper limit of normal (ULN), unless clearly attributable to leukemia involvement. Severe renal impairment, defined as an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m², unless deemed clinically stable and acceptable by the investigator. Any condition that, in the opinion of the investigator, would compromise patient safety or interfere with the interpretation of pharmacokinetic or pharmacodynamic results.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Venetoclax plasma exposure, including area under the concentration–time curve (AUC) and trough concentration (Cmin), and the effect of concomitant posaconazole on these pharmacokinetic parameters. | — |
Secondary
| Measure | Time frame |
|---|---|
| The quantitative relationship between posaconazole exposure and venetoclax exposureModel-based predictions of venetoclax exposure under different posaconazole concentration rangesEstimated venetoclax use and associated medication costs with and without posaconazole-guided dose adjustments | — |
Countries
Netherlands
Contacts
Public ContactE Leegwater
Radboud Universitair Medisch Centrum
Outcome results
None listed