Venetoclax plus azacitidine versus standard intensive chemotherapy for patients with newly diagnosed acute myeloid leukemia (AML) and NPM1 mutations eligible for intensive treatment (VINCENT)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 146
- 试验地点
- 25
- 主要终点
- Modified Event-free survival (mEFS)
研究概览
简要总结
To compare efficacy of azacitidine plus venetoclax with standard intensive therapy
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Signed informed consent
- •Newly diagnosed CD33-positive AML with NPM1 mutation according to WHO criteria
- •Age 18-70 years
- •Fit for intensive chemotherapy, defined by:
- •Adequate hepatic function: ALAT/ASAT/Bilirubin ≤ 2.5 x ULN unless considered due to leukemic organ involvement (Note: Subjects with Gilbert's Syndrome may have a bilirubin > 2.5 × ULN per discussion between the investigator and Coordinating investigator.)
- •Adequate renal function assessed by serum creatinine ≤ 1.5x ULN OR creatinine clearance (by Cockcroft Gault formula) ≥ 50 mL/min
- •WBC < 25 x 109/L (<25,000/µL) (Note: Prior hydroxyurea is permitted to meet this criterion.)
- •Ability to understand and the willingness to sign a written informed consent.
- •Male subjects must agree to refrain from unprotected sex and sperm donation from time point of signing the informed consent until 7 months after the last dose of study drug.
- •Women of childbearing potential must have a negative serum pregnancy test performed within 72 hours before first dose of study drug.
排除标准
- •Activating FLT3 mutation
- •Known positivity for human immunodeficiency virus (HIV), and history of active or chronic infectious hepatitis unless serology demonstrates clearance of infection (i.e. PCR undetectable viral load for hepatitis).
- •Inability to swallow oral medications
- •Any malabsorption condition
- •Cardiovascular disability status of New York Heart Association (NYHA) Class ≥ 2, unstable coronary artery disease (MI more than 6 months prior to study entry is permitted); serious cardiac ventricular arrhythmias requiring anti-arrhythmic therapy (Note: Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or anginal pain).
- •Relapsed or refractory AML
- •AML after antecedent myelodysplasia (MDS) with prior cytotoxic treatment
- •Prior history of malignancy, other than MDS, unless the subject has been free of the disease for equal to or greater than 1 year prior to start of study treatment (exceptions are basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or of the breast, incidental histologic finding of prostate cancer (T1a or T1b using the tumor, node, metastasis clinical staging system))
- •Previous treatment with HMA or venetoclax
- •Previous treatment for AML except hydroxyurea
- •Cumulative previous exposure to anthracyclines of > 200 mg/m2 doxorubicin equivalents
- •CNS involvement or extramedullary disease only
- •Known hypersensitivity to excipients of the preparation or any agent given in association with this study including venetoclax, azacitidine, cytarabine, daunorubicin, gemtuzumab-ozogamicin, or mitoxantrone
结局指标
主要结局
Modified Event-free survival (mEFS)
Modified Event-free survival (mEFS)
Event is defined as: 1. Failure to achieve a CR/CRi/CRh after maximum of two induction cycles in the control arm (SOC) or three induction cycles in the investigational arm (VEN+AZA), i.e. primary induction failure
Event is defined as: 1. Failure to achieve a CR/CRi/CRh after maximum of two induction cycles in the control arm (SOC) or three induction cycles in the investigational arm (VEN+AZA), i.e. primary induction failure
Event is defined as: 2. Hematologic relapse after previous CR/CRi/CRh
Event is defined as: 2. Hematologic relapse after previous CR/CRi/CRh
Event is defined as: 3. Molecular failure, defined as either: 3.1 Molecular progression, defined as confirmed ≥ 1 log10 increase of NPM1 MRD level in any two samples in a patient without prior MRD negativity or 3.2 Molecular relapse after previous MRD negativity, defined as confirmed ≥ 1 log10 between two consecutive positive samples in a patient who was previously tested as MRD negative
Event is defined as: 3. Molecular failure, defined as either: 3.1 Molecular progression, defined as confirmed ≥ 1 log10 increase of NPM1 MRD level in any two samples in a patient without prior MRD negativity or 3.2 Molecular relapse after previous MRD negativity, defined as confirmed ≥ 1 log10 between two consecutive positive samples in a patient who was previously tested as MRD negative
Event is defined as: 4. Death
Event is defined as: 4. Death
次要结局
- Cumulative occurrence of grade 3 and 4 adverse events (tolerability)
- Rate of morphologic CR and CR/CRi/CRh with MRD negativity
- MRD as detected by MFC and MRD kinetics in NPM1 real-time PCR
- Rate of molecular response and molecular persistence
- Relapse-free survival and overall survival
- Early mortality (14 d, 30 d, 60 d from start of induction)
- Change in Health-related quality of life (QoL)
- Cumulative health-care resource use at 12 and 24 months
研究者
Prof. Dr. med. Christoph Röllig
Scientific
Technische Universitaet Dresden