An observational study in Adult Acute Myeloid Leukemia, sponsored by University Hospital, Caen. Recruiting at 1 site in France. Open to participants aged 60 Years to 90 Years. Per ClinicalTrials.gov, last updated 2025-02-28.
Sponsored by University Hospital, Caen · Observational
Background: In combination with hypomethylating drugs, venetoclax has recently changed the therapeutic management of patients with newly diagnosed acute myeloid leukemia (AML) for whom standard induction chemotherapy was not an option. Over and above the clinical benefits of this combination, the data show that more than half the patients did not show remission criteria, even after the first month's exposure to venetoclax.
Hypothesis: To compare the mean residual venetoclax plasma concentrations obtained in patients who went into complete composite remission versus those who did not go into remission at the end of the first cycle of venetoclax + azacitidine treatment.
Method: According to the French law, this is a multicenter, non-comparative, open-label, single-arm, interventional study with minimal risks and constraints. Selection, information and inclusion will concern adult patients (≥60 years) with a confirmed diagnosis of AML according to ELN 2022 guidelines. Included patients will be treated as standard care with a combination of venetoclax+azacitidine. This research protocol will not modify their usual care.
5,442 studies on the registry are indexed under Leukemia; 637 are open to participants now.
This study's planned enrollment of 100 is below the median of 120 across 744 observational studies indexed under Leukemia.
Browse Leukemia studies →University Hospital, Caen is the lead sponsor of 505 studies on the registry; 80 are open to participants now.
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adult patients with untreated AML and ineligible for standard cytarabine and anthracycline induction therapy
Subject must be ineligible for standard cytarabine and anthracycline induction therapy according to the following criteria:
OR subject aged between 60 and 74 with at least one of the following comorbidities:
Exclusion Criteria:
Subject to an uncontrolled intercurrent disease such as:
Patients in composite complete remission following the first cycle of venetoclax (400 mg/day, orally, after a ramp-up phase of the first 3 days) + azacytidine (75mg/m²,intravenous, at the start of each cycle from day 1 to day 7)
Biological: Blood sampling for venetoclax drug dosage (venous puncture)
Patients not in composite complete remission following the first cycle of venetoclax (400 mg/day, orally, after a ramp-up phase of the first 3 days) + azacytidine (75mg/m²,intravenous, at the start of each cycle from day 1 to day 7)
Biological: Blood sampling for venetoclax drug dosage (venous puncture)
8 blood samples for venetoclax and azole antifungal drugs identification and dosage will be taken by venous and capillary punctures throughout management of patients
Also known as: Biological: Capillary Blood sampling for venetoclax drug dosage with Volumetric Absorptive Microsampling (VAMS™) technology with Mitra® device (CE-IVD /IVDR), Biological: Blood sampling for azole antifungal drug dosage (venous puncture)
Comparison of mean plasma residual concentration of venetoclax
To compare the mean plasma residual concentration (ng/mL) of venetoclax (determined by LC-MS-MS) between patients who have entered composite complete remission (defined by the presence of remission criteria ≥ CRi, according to ELN 2022 guidelines) versus those who have not at the end of the first cycle of venetoclax+azacitidine treatment.
Time frame: 1 month
Study relationship between mean plasma residual concentration of venetoclax and remission occurrence
To estimate mean residual plasma concentrations (Cres, ng/mL) of venetoclax and azole antifungals during patients' usual care. Then study the relationship between mean venetoclax Cres and the achievement (or non-achievement) of remission over time (according to ELN 2022 guidelines) .
Time frame: 24 months
Study performance of mean venetoclax Cres
To evaluate the performance (ROC curve) of mean venetoclax Cres (ng/mL) as a predictive biomarker of event-free survival (EFS) at 6 and 12 months.
Time frame: 6 and 12 months
Study survival
To estimate event-free survival (EFS), relapse-free survival (RFS) and overall survival (OS).
Time frame: 24 months
Study early deaths
To estimate the proportion of early deaths at 30 and 60 days post-inclusion.
Time frame: 24 months
Study the variability of plasma venetoclax and antifungal concentrations over time
To estimate the inter-individual (IIV) and intra-individual (IOV) variability of plasma venetoclax and antifungal concentrations over time.
Time frame: 24 months
Study the impact of parameters in uni- and multivariate analyses.
To estimate the impact of the following parameters to the diagnosis of remission or Cres (venetoclax): * patient characteristics: age \[years\], BMI (\[kg/m²\], sex\[male vs female\], ECOG \[1,2 or 3\], comorbidities reported in inclusion criteria, number of cytopenia grade\>2, according to CTCAE v5, white blood cell count \[G/L\], creatininemia \[µmol/L\], cytoreduction (yes or not). * disease: AML classification (ELN 2022 guidelines), blast counts (G/L), cytogenetic status (fail, normal or not) and report, genetic status and report, abnormal rearrangement of genetic material and report. * and (co-)treatments of interest: fluconazole, isavuconazole, itraconazole, posaconazole, voriconazole, cannabidiol, ciclosporine, clarithromycine, diltiazem, ritonavir, verapamil,milk thistle, licorice; bosentan, carbamazépine, efavirenz, enzalutamide, felbamate, phénytoïne, phénobarbital, rifampicine, St. John's wort, grapefruit, bitter orange, star fruit).
Time frame: 24 months
Study adverse events of interest
To compare mean venetoclax Cres between patients who have experienced one or more of the 5 AEs of interest versus those who have not over time.
Time frame: 24 months
ancillary study 1: study a medical device (VAMS Mitra, Neoteryx) to collect blood capillary sample as an alternative to venous puncture
To compare venetoclax Cres (ng/mL) values obtained with the Mitra® (Neoteryx) medical device (CE) with those obtained after conventional venipuncture (ng/mL).
Time frame: 24 months
ancillary study 2: study exposure of plasma venetoclax over 24h
To compute the total integrated area under the plasma venetoclax concentration-time curve (AUC) over 24h in 30 patients cared in CHU of Caen only and to identify the best time of sampling. Pharmacokinetic sampling (day 2 or 3 of cycle 2): Cres (prédose, ng/mL) and post-dose: 2h, 4h, 6h, 8h, 12h, 18h, 24h.
Time frame: 24 months
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University Hospital, Caen