Clinical trial NCT06045819: Relation Between Venetoclax Plasma Concentration and Remission in Adults with Acute Myeloid Leukemia (PREDICLAX)
Official title: Study of the Association Between Residual Venetoclax Plasma Concentration and Composite Complete Remission in Adults with Newly Diagnosed Acute Myeloid Leukemia Ineligible for Intensive Chemotherapy (PREDICLAX)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Adult Acute Myeloid Leukemia
Lead sponsor: University Hospital, Caen
Sponsor class: OTHER
First posted: 2023-09-21
Enrollment: 100
Sex: ALL
Minimum age (years): 60
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: adult patients with untreated AML and ineligible for standard cytarabine and anthracycline induction therapy

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Subject must have a confirmed diagnosis of previously untreated AML (ELN 2022 criteria) within 28 days of the onset of symptoms. Only previous cytoreductive treatments (e.g. hydroxyurea) are authorized.
2. Subject must be ineligible for standard cytarabine and anthracycline induction therapy according to the following criteria:

   * Subject aged ≥ 75 years.
   * OR subject aged between 60 and 74 with at least one of the following comorbidities:

     * ECOG performance status: of 2 or 3.
     * cardiac history: heart failure requiring treatment, left ventricular ejection fraction ≤ 50%, chronic stable angina.
     * carbon monoxide diffusion capacity ≤ 65% or forced expiratory volume in one second ≤ 65%.
     * creatinine clearance between 30 and 45 mL/min/m².
     * liver damage (not related to AML) with total bilirubin between 1.5 and 3 × upper normal limit.
     * any other comorbidity deemed by the physician to be incompatible with standard induction chemotherapy.
3. Patients are eligible for the recommended standard treatment, i.e. a combination of venetoclax and a hypomethylating agent.
4. Subjects must voluntarily sign and date an informed consent form authorized by the relevant authorities.
5. The participation of the subject in another interventional study not interfering with the pathophysiological, pharmacological and clinical rationale of this protocol is possible.

Exclusion Criteria:

1. blood leukocytes \>25 G/L.
2. Subject has already received anticancer treatment (drugs, surgery, radiotherapy) for AML, hematological malignancy or malignant cancer (within the last 2 years).
3. Subjects with AML with central nervous system involvement or promyelocytic type (AML-M3).
4. Subject to an uncontrolled intercurrent disease such as:

   * infection (viral, bacterial or fungal) requiring treatment;
   * symptomatic congestive heart failure;
   * unstable angina pectoris
   * cardiac arrhythmia
   * psychiatric illness or drug addiction that would limit compliance with study requirements (risk of treatment non-adherence or low venous capital).
5. Documented hypersensitivity to the drugs used to treat the subject.
6. Subject has been exposed to potent CYP450 inducers or inhibitors (including grapefruit, Seville oranges) within 7 days prior to treatment initiation.

Primary outcomes:
measure: Comparison of mean plasma residual concentration of venetoclax
timeFrame: 1 month
Secondary outcomes:
measure: Study relationship between mean plasma residual concentration of venetoclax and remission occurrence
timeFrame: 24 months
measure: Study performance of mean venetoclax Cres
timeFrame: 6 and 12 months
measure: Study survival
timeFrame: 24 months
measure: Study early deaths
timeFrame: 24 months
measure: Study the variability of plasma venetoclax and antifungal concentrations over time
timeFrame: 24 months
measure: Study the impact of parameters in uni- and multivariate analyses.
timeFrame: 24 months
measure: Study adverse events of interest
timeFrame: 24 months
Other outcomes:
measure: ancillary study 1: study a medical device (VAMS Mitra, Neoteryx) to collect blood capillary sample as an alternative to venous puncture
timeFrame: 24 months
measure: ancillary study 2: study exposure of plasma venetoclax over 24h
timeFrame: 24 months
Locations:
city: Caen
country: France
facility: CHU de Caen
Study officials:
affiliation: University Teaching Hospital of Caen
name: Pierre-Marie Morice, PharmD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Teaching Hospital of Caen
name: Sylvain Chantepie, MD
role: PRINCIPAL_INVESTIGATOR
References: