Effect of Priming With Granulocyte-Macrophage Colony-Stimulating Factor During Chemotherapy and Comparison of Timed Sequential Chemotherapy vs 4 Courses of High Dose Cytarabine as Consolidation in Younger Adults With Newly Diagnosed AML
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 473
- 主要终点
- Assessing the potential value of the daily administration of GM-CSF during induction chemotherapy and post-induction for analyzing and comparing the arms with and without GM-CSF: EFS, % of CR, duration of remission, OS and toxicity of each treatment.
研究概览
简要总结
The purpose of this study is:
- To compare priming with Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) during induction and consolidation courses versus no priming.
- To compare as consolidation timed sequential chemotherapy versus four courses of high dose cytarabine.
详细描述
Patients aged 15-50 are enrolled and randomly assigned to receive GM-CSF or no GM-CSF during all remission-induction and consolidation courses of chemotherapy. Induction chemotherapy consists of a timed-sequential chemotherapy including a first sequence of chemotherapy combining daunorubicin, 80 mg/m2 per day, administered IV as a short infusion over 3 days (days 1-3), and cytarabine, 500 mg/m2 per day IV as a continuous infusion over the same period. The second sequence, administered after 4-day free interval, consists of mitoxantrone, 12 mg/m2 per day, administered IV as a short infusion over 2 days (days 8 and 9), and cytarabine, 500 mg/m2/12h, administered as a 3-hour infusion for 3 days (days 8-10). Salvage therapy consists of cytarabine, 3 g/m2/12h on days 1,3,5,7, combined with amsacrine, 100mg/m2 per day on days 1 to 3. GM-CSF (Leucomax, recombinant human GM-CSF from Escherichia Coli, Schering Plough, Kenilworth,N.J., USA) is given at a dose of 5µg/kg per day, intravenously beginning at day 1 of each chemotherapy course and continuing until the last day of chemotherapy of each course.
Patients who achieve CR after induction chemotherapy or salvage therapy are randomly assigned to consolidation courses consisting of either a timed sequential chemotherapy similar to that of the ALFA-9000 trial (P2 arm) or the CALGB postremission chemotherapy (P1 arm), which includes 4 cycles of high-dose cytarabine, followed by 4 additional maintenance courses.
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
- 15 Years 至 50 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A morphologically proven diagnosis of AML according to the WHO classification
- •Serum creatinine < 2N; AST and ALT < 2.5N; total bilirubin < 2N (unless related to the underlying disease).
- •ECOG performance status 0 to
- •Women of child-bearing must use acceptable contraceptive methods, and must have a negative serum or urine pregnancy test within 2 weeks prior the beginning treatment on this trial.
- •Must be able and willing to give written informed consent
排除标准
- •Patients with M3-AML. Patient with AML following diagnosed myeloproliferation or patient with prior history of MDS known for more than 3 months. Patients with AML secondary to previous treatment with cytotoxic chemotherapy or radiotherapy (therapy-related AML).
- •Patient presenting any diagnosis of uncontrolled or metastatic tumor.
- •Patients with uncontrolled severe infection,
研究组 & 干预措施
EMA+GM-CSF
- Daunorubicine (CérubidineR) : 80 mg/m2/jour IV over 30 min from day 1 to day 3,
- AraC (AracytineR) : 500 mg/m2/jour IV from day 1 to day 3,
- Mitoxantrone (NovantroneR) : 12 mg/m2/jour IV over 30 min from day 8 to 9
- AraC (AracytineR) : 500 mg/m2/12h IV over 3 hours from day 8 to day10.
- GM-CSF (LeucomaxR): 5 µg/kg/jour IV over 6 hours from day 1 to day 10.
干预措施: GM-CSF (Drug)
EMA without GM-CSF
- Daunorubicine (CérubidineR) : 80 mg/m2/jour IV over 30 min from day 1 to day 3,
- AraC (AracytineR) : 500 mg/m2/jour IV from day 1 to day 3,
- Mitoxantrone (NovantroneR) : 12 mg/m2/jour IV over 30 min from day 8 to 9
- AraC (AracytineR) : 500 mg/m2/12h IV over 3 hours from day 8 to day10.
干预措施: GM-CSF (Drug)
HD AraC+ GM-CSF
- AraC (Aracytine) : 3 g/m2/12h IV (3 hours) on days 1, 3 , 5
- GM-CSF :5 µg/kg/d IV (6 hours) from day1 to day 5
干预措施: GM-CSF (Drug)
HD-AraC without GM-CSF
- AraC (Aracytine) : 3 g/m2/12h IV (3 hours) on days 1, 3 , 5
干预措施: GM-CSF (Drug)
结局指标
主要结局
Assessing the potential value of the daily administration of GM-CSF during induction chemotherapy and post-induction for analyzing and comparing the arms with and without GM-CSF: EFS, % of CR, duration of remission, OS and toxicity of each treatment.
时间窗: 72 months
次要结局
- Evaluate the effectiveness on DFS of a single course of consolidation using a very intensive sequential chemotherapy with mitoxantrone, AraC and etoposide feasible compared to 4 courses of high dose AraC followed of 4 courses of maintenance.(72 months)