Relation Between Venetoclax Plasma Concentration and Remission in Adults with Acute Myeloid Leukemia (PREDICLAX)

NCT06045819 | Recruiting DMC FDA Drug

• 1 other identifier: 2023-A01909-36
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Adult Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• 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.

  1 month

Secondary Outcomes (7)

• Study relationship between mean plasma residual concentration of venetoclax and remission occurrence

  24 months

• Study performance of mean venetoclax Cres

  6 and 12 months

• Study survival

  24 months

• Study early deaths

  24 months

• Study the variability of plasma venetoclax and antifungal concentrations over time

  24 months

Other Outcomes (2)

• ancillary study 1: study a medical device (VAMS Mitra, Neoteryx) to collect blood capillary sample as an alternative to venous puncture

  24 months

• ancillary study 2: study exposure of plasma venetoclax over 24h

  24 months

Study Arms (2)

Patients with composite complete remission

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 without composite complete remission

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)

Interventions

Blood sampling for venetoclax drug dosage (venous puncture) BIOLOGICAL

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)

Patients with composite complete remission; Patients without composite complete remission

Eligibility Criteria

• Age: 60 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

adult patients with untreated AML and ineligible for standard cytarabine and anthracycline induction therapy

You may qualify if:

• 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.
• 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.
• Patients are eligible for the recommended standard treatment, i.e. a combination of venetoclax and a hypomethylating agent.
• Subjects must voluntarily sign and date an informed consent form authorized by the relevant authorities.
• The participation of the subject in another interventional study not interfering with the pathophysiological, pharmacological and clinical rationale of this protocol is possible.

You may not qualify if:

• blood leukocytes \>25 G/L.
• Subject has already received anticancer treatment (drugs, surgery, radiotherapy) for AML, hematological malignancy or malignant cancer (within the last 2 years).
• Subjects with AML with central nervous system involvement or promyelocytic type (AML-M3).
• 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).
• Documented hypersensitivity to the drugs used to treat the subject.
• Subject has been exposed to potent CYP450 inducers or inhibitors (including grapefruit, Seville oranges) within 7 days prior to treatment initiation.

Sponsors & Collaborators

• University Hospital, Caen: lead

Study Sites (1)

CHU de Caen

Caen, 14000, France

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

* plasma is obtained through venipuncture * capillary blood is obtained by pricking a finger

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Blood Specimen Collection; Technology

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Technology, Industry, and Agriculture

Study Officials

• Pierre-Marie Morice, PharmD, PhD

  University Teaching Hospital of Caen

  PRINCIPAL INVESTIGATOR

• Sylvain Chantepie, MD

  University Teaching Hospital of Caen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sylvain Chantepie, MD

CONTACT

+33231272107; chantepie-s@chu-caen.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2023
• First Posted: September 21, 2023
• Study Start: April 8, 2024
• Primary Completion: February 1, 2025
• Study Completion: January 1, 2026
• Last Updated: February 28, 2025

Record last verified: 2025-02

Locations

FR (1)