2025-522979-29-00招募中3 期
A randomized phase III, global, multicentre, open label clinical trial comparing Venetoclax Azacitidine and Quizartinib vs Venetoclax and Azacitidine in newly diagnosed acute myeloid leukemia patient´s ineligible for standard induction chemotherapy.
Fundacion PETHEMA50 个研究点 分布在 1 个国家目标入组 350 人开始时间: 2025年12月4日最近更新:
适应症
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 350
- 试验地点
- 50
- 主要终点
- Overall survival (OS)
研究概览
简要总结
To compare the OS rate between the experimental arm with triple combination of venetoclax, azacitidine and quizartinib vs. standard therapy (venetoclax plus azacitidine)
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •The subject must have confirmation of AML by 2022 WHO criteria, previously untreated and be ineligible for treatment with a standard cytarabine and anthracycline based induction regimen due to age and/or comorbidities.
- •Patients must be considered ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to age or co-morbidities defined by the following criteria: - ≥ 75 years of age; - or ≥ 18 to 75 years of age with at least one of the following co-morbidities: • ECOG Performance Status of 2 or 3; • Cardiac history of cardiac heart failure (CHF) requiring treatment or left ventricular ejection fraction (LVEF) >45% and ≤ 55% or chronic stable angina. • DLCO ≤ 65% or FEV1 ≤ 65% and/or significant history of chronic pulmonary obstructive; • Creatinine clearance ≥ 30 mL/min to < 50 ml/min (see Appendix 7); • Moderate hepatic impairment with total bilirubin, SGPT or SGOT > 1.5 to ≤ 3.0 × ULN; • Non active/controlled prior neoplastic disease; • Any other patient´s comorbidity or disease condition that the physician judges to be incompatible with intensive chemotherapy must be reviewed and approved by the Clinical Trial Coordinator before study enrollment (e.g, prior neoplastic disease, high-risk cytogenetics). All patients aged less than 60 years old must be reviewed and approved by Clinical Trial Coordinator before study enrollment.
- •ECOG performance status ≤2 for patients >75 years, ≤3 for patients ≥ 60 to 75 years of age.
- •Male subjects who are sexually active, must agree, from Study Day 1 through at least 120 days after the last dose of study drug, to practice the protocol specified contraception (see Section 7.9).
- •Female subjects must be either postmenopausal for at least 1 year before screening OR permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy) or Women of Childbearing Potential (WOCBP) must agree to practice 1 highly effective method and 1 additional effective (barrier) method of contraception, at the same time, from the time of signing the informed consent through 7 months after the last dose of study drug (female and male condoms should not be used together), or Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception). Female subjects of childbearing potential must have negative results for pregnancy test performed and must not be lactating and breastfeeding.
- •Subject must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study specific procedures, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
排除标准
- •Age <18 years old at screening.
- •Contraindications for Azacitidine, Quizartinib or Venetoclax (such as history of hypersensitivity to any excipients in Azacitidine, Quizartinib, or Venetoclax).
- •Known central nervous system (CNS) active leukemia, including cerebrospinal fluid positive for AML blasts.
- •Prior treatment with any investigational drug or device within 14 days prior to Randomization (within 2 weeks for investigational or approved immunotherapy) or currently participating in other investigational interventional procedures.
- •Known uncontrolled or significant cardiovascular disease, including any of the following: a) Bradycardia of less than 50 beats per minute, unless the subject has a pacemaker; b) QTcF interval >450 msec in males, >470 in female patients; c) Diagnosis of or suspicion of long QT syndrome (including family history of long QT syndrome); d) Systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg; e) History of clinically relevant ventricular arrhythmias (eg, ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes); f) History of second (Mobitz II) or third degree heart block (subjects with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker); g) History of uncontrolled angina pectoris or myocardial infarction within 6 months prior to Screening; h) History of New York Heart Association Class 3 or 4 heart failure; i) Known history of LVEF ≤45%; j) Complete left bundle branch block; k) Severe aortic stenosis
- •Prior therapy for AML (except hydroxiurea, or maximum 1 gram/sqm per 2 days of cytarabine allowed to control hyperleukocytosis during the screening period).
- •Subject must not have consumed grapefruit, grapefruit products, Seville oranges (including marmalade-containing Seville oranges), or star fruit within 3 days before anticipated first dose of Venetoclax and must consent not to consume through the last dose of Venetoclax.
- •Active acute or chronic systemic fungal, bacterial, or viral infection not well controlled by antifungal, antibacterial or antiviral therapy at physician discretion.
- •Known active clinically relevant liver disease (eg, active hepatitis B, or active hepatitis C)
- •Known history of human immunodeficiency virus (HIV).
- •Uncorrected Grade 3 or 4 hypokalemia, hypomagnesemia or hypocalcemia (Subjects with Grade 1 or 2 electrolyte abnormalities can be enrolled while electrolytes are being corrected).
- •Subject has received prior treatment with hypomethylating agent, FLT3 or BCL2 inhibitors.
- •Uncontrolled hypothyroidism.
- •Confirmed diagnosis of prior myelodysplastic syndrome (MDS) or a myeloproliferative neoplasm (MPN) or MDS/MPNs including CMML, aCML, JMML and others. This exclusion criterion will not be applicable to patients with with FLT3 (allelic ratio >0.03) or NPM1 mutations (as per technical sensitivity threshold of local and/or central laboratory), who can be enrolled.
- •Genetic diagnosis of acute promyelocytic leukemia.
- •Treated (excluding surgery or hormone-therapy) for another malignancy within 6 months before randomization or previously diagnosed with another malignancy and have any evidence of disease which may compromise the administration of investigational treatment schedule.
- •Presence of any severe psychiatric disease or physical condition that, according to the physician´s criteria, contraindicates the inclusion of the patient into the clinical trial.
- •Serum creatinine ≥ 2.5 mg/dL or creatinine clearance < 30 mL/min (unless it is attributable to AML activity).
- •Bilirubin >1.5 times, SGPT or SGOT > 3 times the upper normal limit (unless it is attributable to AML activity).
- •WBC >25 x 109/L before randomization.
结局指标
主要结局
Overall survival (OS)
Overall survival (OS)
次要结局
- Event-free survival (EFS)
- Composite CR (CCR) (best response obtained on study)
- Early mortality (first 30 and 60 days)
- CR, CRh, and CRi with negative measurable residual disease (MRD) by NGS
- CR, CRh, CRi and CCR at 1, 4 and 9 cycles of treatment
- Time to CR, CRh, CRi, CCRCR, CRi, MLFS, PR, PD
- Relapse-free survival (RFS)
- Cumulative incidence of relapse (CIR)
- Duration of response (DoR)
- Quality of life measurements (from the EuroQoL Group EQ-5D-5L and the EORTC QLQ-C30 instruments)
- Medical resources during treatement phase
- Rates of RBC and platelet transfusion independence, duration of RBC transfusion independence and platelet transfusion independence and platelet and RBC transfusion independence
- Minimal residual disease (MRD) by NGS
- Separate analyses in secondary AML, CBF, FLT3-ITD, FLT3 other, NPM1, P53, IDH1/IDH2, and subsets
研究者
Alfonso Santiago
Scientific
Fundacion PETHEMA
研究点 (50)
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