Phase 3 Study to Assess Gemtuzumab, in Combination With Standard Chemotherapy, on MRD Levels, in Adult, 18-60 Years, With Previously Untreated de Novo Fav-interm Risk AML
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 414
- 试验地点
- 48
- 主要终点
- Activity of GO in combination with chemotherapy in terms of MRD negativity achievement
研究概览
简要总结
MRD driven study. Addition of gemtuzumab to conventional chemotherapy to reduce MRD of patients with favorable/intermediate-risk AML. Post-consolidation assessment of MRD.
详细描述
Setting up a multicenter, MRD (Minimal Residual Disease)-driven study that relies on addition of gemtuzumab ozogamicin to conventional chemotherapy to reduce the pre-transplant levels of MRD of patients with favorable/intermediate-risk (according to ELN 2017) AML. Post-consolidation assessment of MRD will be exploited to establish the final risk assignment and to verify whether the delivery of a post remission therapy intensity (AuSCT, Autologous Stem Cell Transplant, vs ASCT, Allogeneic Stem Cell Transplant) of which is MRD-driven will improve the outcome in terms of anti-leukemic efficacy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed written informed consent according to ICH/EU/GCP and national/local laws
- •Patients aged between 18 and 60 years
- •Patients previously untreated for their AML by other chemotherapeutic agents (except for no more than 7 days HU) or radiotherapy
- •Unequivocal diagnosis of de novo AML according to WHO diagnostic criteria (at least 20% blasts in the bone marrow), other than acute promyelocytic leukemia, documented by bone marrow aspiration (or biopsy in case of dry tap) (not supervening after other myeloproliferative disease or myelodysplastic syndromes of ≥ 6 months duration)
- •Patients with favorable-intermediate AML according to ELN 2017 (except for FLT3-ITD/TKD positive AML)
- •WHO performance status 0-3
- •Adequate renal (serum creatinine ≤ 2 x the institutional ULN) and liver (total serum bilirubin ≤ 2 x ULN; serum ALT and AST ≤ 2.5 x ULN) function, unless considered due to organ leukemic involvement
- •Left Ventricular Ejection Fraction (LVEF) ≥ 50%, as determined by echocardiogram
- •Absence of severe concomitant neurological or psychiatric diseases and congestive heart failure or active uncontrolled infection
- •Absence of any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and the follow-up schedule.
排除标准
- •Patients already treated for their AML by other chemotherapeutic agents (except for no more than 7 days HU) or radiotherapy
- •Acute promyelocytic leukemia
- •Blast crisis of chronic myeloid leukemia
- •FLT3-ITD/TKD positive AML
- •AML supervening after other myeloproliferative disease
- •AML supervening after antecedent myelodysplastic syndromes ≥ 6 months duration
- •Therapy-related AML
- •Other active or progressive malignant diseases.
- •Inadequate renal or liver function (metabolic abnormalities > 2-2.5 times the normal upper limit)
- •Severe heart failure requiring diuretics
- •Ejection fraction < 50%
- •Uncontrolled infections
- •Severe concomitant neurological or psychiatric diseases
- •Patients who are pregnant or adults of reproductive potential not employing an effective method of birth control. Women of childbearing potential must have a negative serum pregnancy test within 48 hours prior to administration of chemotherapy. Post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients must agree to employ an effective barrier method of birth control throughout the study and for at least 6 months following discontinuation of study drug.
研究组 & 干预措施
Experimental arm
Induction:
Gemtuzumab 3 mg/m2 day 1,4,7 Daunorubicin 60 mg/m2 day 1-3 Cytosine arabinoside 200 mg/m2 day 1-7
Consolidation:
Gemtuzumab 3 mg/m2 day 1 Daunorubicin 50 mg/m2 day 4-6 Cytosine arabinoside 500 mg/m2 twice a day, day 1-6
Allogeneic transplantation or Autologous transplantation according to MRD level
clinical observation
干预措施: Gemtuzumab Ozogamicin (Drug)
结局指标
主要结局
Activity of GO in combination with chemotherapy in terms of MRD negativity achievement
时间窗: 2 months
Percentage of MRD negativity after consolidation in patients treated in induction and consolidation with GO
次要结局
未报告次要终点