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)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Comparison of mean plasma residual concentration of venetoclax
研究概览
简要总结
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 60 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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.
排除标准
- •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.
研究组 & 干预措施
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)
干预措施: Blood sampling for venetoclax drug dosage (venous puncture) (Biological)
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)
干预措施: Blood sampling for venetoclax drug dosage (venous puncture) (Biological)
结局指标
主要结局
Comparison of mean plasma residual concentration of venetoclax
时间窗: 1 month
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.
次要结局
- Study relationship between mean plasma residual concentration of venetoclax and remission occurrence(24 months)
- Study adverse events of interest(24 months)
- Study performance of mean venetoclax Cres(6 and 12 months)
- Study the variability of plasma venetoclax and antifungal concentrations over time(24 months)
- Study the impact of parameters in uni- and multivariate analyses.(24 months)
- Study survival(24 months)
- Study early deaths(24 months)