Examining the link between venetoclax levels and remission in adults with acute myeloid leukemia

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)

This study is trying to see if the amount of venetoclax in the blood can help predict whether older adults with acute myeloid leukemia will go into remission after treatment.

Quick facts

• Study type: Observational
• Enrollment: 100 (estimated)
• Ages: 60 Years to 90 Years
• Sex: All
• Sponsor: University Hospital, Caen (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Caen)
• Trial ID: NCT06045819 on ClinicalTrials.gov

What this trial studies

This observational study investigates the relationship between venetoclax plasma concentrations and remission outcomes in adults with acute myeloid leukemia (AML) who are ineligible for standard chemotherapy. It aims to compare the mean residual venetoclax levels in patients who achieve complete remission versus those who do not after the first cycle of treatment with venetoclax and azacitidine. The study will involve blood sampling for drug dosage and will include adult patients aged 60 and older with a confirmed diagnosis of AML. The study is conducted in compliance with French law and is designed to have minimal risks for participants.

Who should consider this trial

Good fit: Ideal candidates are adults aged 60 years and older with a confirmed diagnosis of previously untreated acute myeloid leukemia who are ineligible for standard chemotherapy.

Not a fit: Patients who are younger than 60 or those who are eligible for standard induction chemotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could help identify optimal venetoclax dosing to improve remission rates in patients with acute myeloid leukemia.

How similar studies have performed: While this study explores a specific aspect of venetoclax treatment, similar studies have shown promising results in understanding drug concentrations and treatment outcomes in AML.

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.

Where this trial is running

Caen

• CHU de Caen — Caen, France (Recruiting)

Study contacts

• Principal investigator: Pierre-Marie Morice, PharmD, PhD — University Teaching Hospital of Caen
• Study coordinator: Sylvain Chantepie, MD

Conditions Adult Acute Myeloid Leukemia