A PHASE III, MULTICENTRE, RANDOMIZED, OPEN LABEL CLINICAL TRIAL OF AZACYTIDINE (VIDAZA®) VERSUS FLUDARABINE AND CYTARABINE (FLUGA SCHEME) IN ELDERLY PATIENTS WITH NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 289
- 试验地点
- 1
- 主要终点
- Efficacy (overall survival (OS) attained without increasing the therapy-related toxicity or decreasing the patients QoL.
研究概览
简要总结
The hypothesis is that the replacement of the standard fludarabine and cytarabine based therapy by azacytidine could result in an improvement of RFS and OS rates in the experimental arm. To fulfill the medical needs in such frail and elderly population, improvements in terms of atileukemic efficacy in the azacytidine experimental arm should be attained without increasing the therapy-related toxicity or decreasing the patients QoL.
详细描述
This is a multicenter, randomized 1:1, open, and at national level, Phase III clinical trial.
This study will be conducted in 3 phases of different duration:
- Selection phase (up to 14 days from the signature of informed consent): informed consent and review of the inclusion and exclusion criteria performing the relevant assessments.
- Treatment Phase (from the start of treatment until the end of cycle 9): Induction phase (3 cycles) and consolidation phase (cycles 4-9). Study visits during treatment will be weekly during the induction phase (first 3 cycles) and every 2 weeks until the end of the consolidation phase.
- Follow-up phase: monthly monitoring will be performed on all patients until they have completed a minimum of 2 years from the start of treatment, whether or not they continue receiving azacitidine cycles or Mini-Fluga according to the protocol. Following these 24 months, follow-up will be carried out at least quarterly. Patients suffering disease progression or relapse of the disease, or being early withdrawn due to any of the reasons specified in the protocol will be followed-up for survival until the end of the study or until the death of all patients, whichever comes first.
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
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Having voluntarily given informed consent before performing any test that is not part of
- •routine care of patients.
- •Age greater than or equal to
- •Morphological diagnosis of non-promyelocytic AML according to the WHO criteria.
- •Newly diagnosed AML.
- •ECOG performance status <
- •Ability and willingness to comply with the schedule of study visits.
排除标准
- •Genetic diagnosis of acute promyelocytic leukemia.
- •Patients with AML secondary to myelodysplastic syndrome (MDS) or chronic myeloproloferative syndrome who have been previously treated with antileukemic agents
- •(hypomethylating or standard chemotherapy). Treatment with hydroxyurea prior to randomization is allowed.
- •Serum creatinine ≥ 250 mmol / l (≥ 2.5 mg/dL) (unless attributed to AML).
- •Bilirubin, alkaline phosphatase or ALT > 5 times the value of the upper limit of normal (unless attributed to AML) .
- •Presence of an active and/or non controlled pathology different to AML which is severe and life-threatening, that in the investigator's opinion, prevents the subject participation in the study.
- •Other active concomitant malignancy or whose remission is less than one year from the screening day (except carcinoma in situ).
- •Presence of any psychiatric illness or medical condition that, in the investigator's opinion, prevents the subject participation in the study.
- •Life expectancy less than X months.
- •Inability of the patient or his legal representative to understand and voluntarily sign the informed consent form.
研究组 & 干预措施
fludarabine cytarabine
Priming with daily administration of subcutaneous G-CSF (lenograstim or filgrastim 5 mcg /kg / day, days -1, 1 and 2) (not given if hyperleukocytosis> 25 x 109/l), followed by:
- Oral fludarabine (40 mg/m2/day, days 1 to 5) and subcutaneous cytarabine (75mg/m2/day, days 1 to 5) (FLUGA scheme) (fludarabine and cytarabine only days 1 to 4 if age ≥75 years), OR
- Fludarabine (25 mg/m2/day) and cytarabine (75 mg/m2/day infusion of 6 hours) on their intravenous formulations if the patient is hospitalized (patients with hyperleukocytosis or other unfavourable conditions).
Treatment cycles every 28 days
干预措施: Fludarabine (Drug)
fludarabine cytarabine
Priming with daily administration of subcutaneous G-CSF (lenograstim or filgrastim 5 mcg /kg / day, days -1, 1 and 2) (not given if hyperleukocytosis> 25 x 109/l), followed by:
- Oral fludarabine (40 mg/m2/day, days 1 to 5) and subcutaneous cytarabine (75mg/m2/day, days 1 to 5) (FLUGA scheme) (fludarabine and cytarabine only days 1 to 4 if age ≥75 years), OR
- Fludarabine (25 mg/m2/day) and cytarabine (75 mg/m2/day infusion of 6 hours) on their intravenous formulations if the patient is hospitalized (patients with hyperleukocytosis or other unfavourable conditions).
Treatment cycles every 28 days
干预措施: Cytarabine (Drug)
fludarabine cytarabine
Priming with daily administration of subcutaneous G-CSF (lenograstim or filgrastim 5 mcg /kg / day, days -1, 1 and 2) (not given if hyperleukocytosis> 25 x 109/l), followed by:
- Oral fludarabine (40 mg/m2/day, days 1 to 5) and subcutaneous cytarabine (75mg/m2/day, days 1 to 5) (FLUGA scheme) (fludarabine and cytarabine only days 1 to 4 if age ≥75 years), OR
- Fludarabine (25 mg/m2/day) and cytarabine (75 mg/m2/day infusion of 6 hours) on their intravenous formulations if the patient is hospitalized (patients with hyperleukocytosis or other unfavourable conditions).
Treatment cycles every 28 days
干预措施: Lenograstim (Drug)
fludarabine cytarabine
Priming with daily administration of subcutaneous G-CSF (lenograstim or filgrastim 5 mcg /kg / day, days -1, 1 and 2) (not given if hyperleukocytosis> 25 x 109/l), followed by:
- Oral fludarabine (40 mg/m2/day, days 1 to 5) and subcutaneous cytarabine (75mg/m2/day, days 1 to 5) (FLUGA scheme) (fludarabine and cytarabine only days 1 to 4 if age ≥75 years), OR
- Fludarabine (25 mg/m2/day) and cytarabine (75 mg/m2/day infusion of 6 hours) on their intravenous formulations if the patient is hospitalized (patients with hyperleukocytosis or other unfavourable conditions).
Treatment cycles every 28 days
干预措施: Filgastrim (Drug)
Azacitidine
Subcutaneous Azacitidine 75 mg/m2/day, days 1 to 7. Treatment cycles every 28 days.
干预措施: Azacitadine (Drug)
结局指标
主要结局
Efficacy (overall survival (OS) attained without increasing the therapy-related toxicity or decreasing the patients QoL.
时间窗: 4 years
To evaluate the overall survival (OS) in one year treatment with 2 first-line regimens in newly diagnosed elderly patients: 3 cycles of induction chemotherapy based on fludarabine and cytarabine (FLUGA scheme) followed by maintenance with reduced doses(Mini-FLUGA) (standard treatment arm) versus subcutaneous azacitidine cycles (experimental treatment arm).
次要结局
- Efficacy (Event free survival (EFS)(4 years)
- Efficacy (Duration of remission.)(4 years)
- Efficacy (Overall survival) Efficcacy(3 years)
- Safety (Compare hematologic and non-hematologic toxicity)(3 years)