A Phase 3, Prospective, Randomized Multi-center Intervention Trial of Early Intensification in AML Patients Bearing FLT3 Mutations Based on Peripheral Blast Clearance: A MYNERVA-GIMEMA Study
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 172
- 试验地点
- 20
- 主要终点
- Event Free Survival
研究概览
简要总结
Prospective, multi-center, interventional, randomized, open clinical trial for the treatment of acute myeloid leukemia with FLT3 mutations customized upon the prognostic parameter PBC
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with de novo AML, untreated, newly diagnosed, according to WHO 2016 criteria
- •Presence of a mutation of FLT3 gene, either ITD and/or TKD
- •Adequate availability of diagnostic biologic material for full cytological, cytogenetic, genetic and immunophenotypic disease characterization according to ELN criteria.
- •Presence of morphologically identifiable blasts on peripheral blood at diagnosis
- •Presence of a Leukemia-associated aberrant immune-phenotype (LAIP) as assessed by MFC (multiparametric flow cytometry) at diagnosis
- •Age between 18 and 65 years, included
- •ECOG performance status 0-2 or disease-related reversible ECOG 3 score following adequate supportive care.
- •Signed written informed consent according to ICH/EU/GCP and national local laws
排除标准
- •Diagnosis of acute promyelocytic leukemia
- •Diagnosis of AML with t(8;21)(q22:q22)/RUNX1-RUNX1T1 and t(16;16)(p13:q22) or inversion of chromosome 16 (16)(p13q22)/CBFB-MYH11; in case of suspicion of CBF-related AML due to morphological and/or immunophenotypic features, specific FISH or molecular testing is strongly recommended in accordance with WHO criteria3,157
- •Patients with LVEF less than 45% (by echocardiogram or MUGA)
- •Pre-existing, uncontrolled pathology such as heart failure (congestive/ischaemic, acute myocardial infarction within the post 3 months, untreatable arrhythmias, NYHA classes III and IV), sever liver disease with total bilirubin ≥2,5 x ULN and/or ALT>3 ULN (unless attributable to AML), acute or chronic pancreatitis, kidney function impairment with serum creatinine ≥2,5 (unless attributable to AML) and severe neuropsychiatric disorder that impairs the patient's ability to understand and sign the informed consent or to cope with the intended treatment plan. For altered liver, pancreas and kidney function tests, eligibility criteria can be reassessed at 24-96 hours, following the institution of adequate supportive measures.
- •Uncontrolled bacterial or fungal infections
- •QTc >470 msec on screening ECG (Fridericia's formula)
- •A history of cancer that is not in remission phase following surgery and/or chemotherapy and/or radiotherapy with life expectancy < 1 year.
- •Pregnancy declared by the patient herself. A pregnancy test is performed at diagnosis and, if applicable, before allogeneic HSCT . Female and male patients who are fertile must agree to use an effective form of contraception with their sexual partners from enrollment through 4 months after the end of treatment.
研究组 & 干预措施
Standard clinical treatment
Patients will complete "3+7" + Midostaurin induction course.
干预措施: Midostaurin (Drug)
Standard clinical treatment
Patients will complete "3+7" + Midostaurin induction course.
干预措施: Cytarabine (Drug)
Standard clinical treatment
Patients will complete "3+7" + Midostaurin induction course.
干预措施: Daunorubicin (Drug)
Experimental treatment
The experimental arm will provide 2 main modifications compared to standard:
i) immediate switch to intensified induction with high-doses Cytarabine (on days 5, 6 and 7 of induction) ii) early allocation to high-risk disease category to be refined according to ELN stratification and post induction MRD status
干预措施: Daunorubicin (Drug)
Experimental treatment
The experimental arm will provide 2 main modifications compared to standard:
i) immediate switch to intensified induction with high-doses Cytarabine (on days 5, 6 and 7 of induction) ii) early allocation to high-risk disease category to be refined according to ELN stratification and post induction MRD status
干预措施: Midostaurin (Drug)
Experimental treatment
The experimental arm will provide 2 main modifications compared to standard:
i) immediate switch to intensified induction with high-doses Cytarabine (on days 5, 6 and 7 of induction) ii) early allocation to high-risk disease category to be refined according to ELN stratification and post induction MRD status
干预措施: Cytarabine HD (Drug)
结局指标
主要结局
Event Free Survival
时间窗: 2,5 years
Improvement of outcome measured as event-free survival (EFS) in patients with FLT3+ acute myeloid leukemia who are predicted to have low chemosensitivity, as defined upon the biomarker "peripheral blast clearance (PBC)", following the application of an early intensification of overall treatment, both in induction (high-doses delivery) and in consolidation (allocation to allogeneic transplant) phase, compared with standard regimens
次要结局
- DFS(2 years)
- Adverse events rate(2,5 years)
- Rate of death in aplasia(2 months)
- Neutrophil recovery(2 months)
- CR rate(6 months)
- OS(2 years)
- platelet recovery(2 months)
- CIR(2 years)
- MRD assessment(6 months)