Validation Study of a New Cytokine-based Dynamic Stratification Based on FLt3 Ligand Plasma Concentration Kinetic Profile and IL-6 Concentration During Induction of Acute Myeloid Leukemia
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 201
- 试验地点
- 25
- 主要终点
- Confirm that the combination of the kinetic profile of FLT3L plasma levels and the IL-6 plasma level at day22 during induction in AML patients is predictive of overall survival.
研究概览
简要总结
The investigators have recently demonstrated the strong impact in terms of survivals of Fms-like tyrosine kinase 3 ligand (FL) levels evaluated during intensive induction in acute myeloid leukemia (AML) patients. Indeed, three FL kinetic profiles were delineated: i) sustained increase of FL concentrations between day (D) 1 and D22 (FLI group, n=26, good-risk), ii) increase from D1 to D15, then decrease at D22 (FLD group, n=22, intermediate-risk) and iii) stagnation of low levels (<1000 pg/mL, FLL group, n=14, high-risk). However, with longer follow-up, the investigators have observed that FLI and FLD shared similar outcomes while FLL sub-group kept a very bad prognostic.
Because serum samples from this previous study (called the FLAM/FLAL study) had been frozen-stored, the investigators were able to conduct an ancillary study assessing the potential impact of the kinetics of 6 other cytokines: TNFalpha, stem-cell factor, IL-1beta, IL-6, IL-10 and granulocyte-monocyte colony-stimulating factor (GM-CSF).. Only Il-6 level at D22 (< or >15.5 pg/mL) was associated with outcome allowing to distinguish between higher and lower survivals within the combined FLI/FLD sub-group.
A new prognostic risk-stratification can thus be proposed as follows: FLI/FLD with IL-6 <15.5 pg/mL (favorable), FLI/FLD with IL-6 >15.5 pg/mL (intermediate) and FLL (high-risk).
The aim of this new FLAMVAL study is to validate prospectively in a larger and independent cohort this prognostic risk-stratification i.e. that kinetic profile of FLT3L plasma level from D1 to D22 and Il6 plasma level at day 22 during induction of AML patients are predictive of overall and disease free survivals.
For that purpose, 201 newly diagnosed AML patients treated intensively in the 25 centres of the French Innovative Leukemia Organisation (FILO) will be included in the FLAMVAL study.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >= 18 years old
- •Confirmed diagnosis of AML according to World Health Organization (WHO) 2016 classification (Arber et al., 2016)
- •Non previously treated AML (first-line therapy)
- •Patients eligible to standard 3+7 induction chemotherapy with a minimum of 3 days of daunorubicin at 45mg/m2/day or a minimum of 5 days of idarubicin at 8mg/m2/day and a minimum of 7 days of cytarabin at 100mg/m2/day
- •Patients receiving any "third drug" combined to the "3+7" scheme, i.e. lomustine, corticotherapy, elthrombopag, gemtuzumab-ozogamycin, any FLT3 inhibitors… are eligible
- •Patients receiving CPX-351 (Vyxeos ®) are eligible
- •Patients requiring leukapheresis are eligible
- •Signed informed consent
排除标准
- •Patients diagnosed with Acute Promyelocytic Leukemia (AML-3)
- •Adults under guardianship, subjects under protection.
结局指标
主要结局
Confirm that the combination of the kinetic profile of FLT3L plasma levels and the IL-6 plasma level at day22 during induction in AML patients is predictive of overall survival.
时间窗: 2 years
time from day 1 of induction to the date of death or of last follow-up
次要结局
- Study Immune reconstitution during induction(2 years)
- Confirm that the new FL/IL6 risk-model predicts leukemia free survival in first-line AML patients.(2 years)
- Study the impact of the new FL/IL6 risk-model in FLT3 ITD or TKD patients receiving or not FLT3 inhibitors(2 years)
- Compare the prognostic impact of the new FL/IL6 risk-model with the impact of other parameters known to predict outcome in AML(2 years)