Risk Adapted Treatment for Primary AML in Adults up to the Age of 60 Years.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 354
- 试验地点
- 19
- 主要终点
- Complete remission rate.
研究概览
简要总结
In a protocol of treatment of AML used in 1994 for adults with AML up to the age of 50 years, the Spanish CETLAM group showed a complete remission rate 75 % using the combination of daunorubicin (60 mg/m2, 3 days) plus conventional dose cytarabine (100mg/m2/day in continuous infusion during 7 days) and etoposide (100mg/m2 IV/day 3 days). If idarubicin (10 mg/m2, 3 days) was administered instead of daunorubicin, the complete remission (CR) rate in adults up to 60 years was 75%. To improve the proportion of CRs and to decrease relapse rate appearing in 50% of patients, the phase II AML-99 trial includes intermediate dose-cytarabine during induction and risk-adapted post remission treatment based on the improvement in prognostic characterization of AML and the implementation of novel transplantation techniques.
详细描述
Induction chemotherapy: idarubicin (12mg/m2/day intravenous), intermediate-dose cytarabine (500mg/m2/12h, intravenous) and etoposide (100mg/m2/day, intravenous) in 3+7+3 schedule. This induction therapy is repeated if complete remission (CR) is not achieved after the first course of treatment.
Consolidation therapy: mitoxantrone (12mg/m2/day, intravenous, days 4, 5 and 6) and intermediate-dose cytarabine (500mg/m2/12h from day 1 to 6).
Risk-stratification according to cytogenetics, courses to CR and availability of an HLA-identical sibling:
- Patients in the favorable cytogenetics group [t(8;21), inv(16) or t(16;16)] are treated with high-dose cytarabine (3g/m2/12h, intravenous, days 1, 3 and 5).
- Patients in intermediate cytogenetics group (normal karyotype and a single course to achieve the CR) receive an autologous peripheral blood stem cell (PBSC) transplant, regardless of having an HLA-identical sibling.
- The remaining patients are considered in the high-risk group and are treated with autologous or allogeneic PBSC transplantation depending on the availability of a sibling donor. In allotransplants, CD34+ cell selection of hematopoietic cells is performed.
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
- •Patients with newly diagnosed AML, classified by FAB criteria
- •Age not superior to 60 years
- •Verbal informed consent for the chemotherapy and written for the mobilization and stem cell transplantation
排除标准
- •Patients treated previously for its AML with other chemotherapy different from hydroxyurea
- •Acute promyelocytic leukemia (M3)
- •Chronic myeloid leukemia in blastic crisis
- •Leukemias appearing after other myeloproliferative processes
- •Leukemias surviving after myelodysplastic syndromes with more than 6 months of evolution
- •Presence of other neoplastic disease in activity
- •Secondary AML which had appeared after cured malignancies (for instance Hodgkin disease) and those who are still exposed to alkylant agents or radiation
- •Renal and hepatic abnormal function with creatinine values and/or bilirubin two times higher than the normal threshold, except when this alteration could be attributed to the leukemia
- •Patients with a fraction of ejection very low (inferior to 40%), symptomatic cardiac insufficiency or both
- •Patients with a grave concomitant neurological or psychiatric disease
- •Positivity of HIV (donor and/or receptor)
研究组 & 干预措施
Risk-adapted postremission treatment
Ara-C, autologous transplantation, Allogeneic HLA-identical sibling transplantation depending on risk factors (cytogenetics, courses to CR)and availability of an HLA-identical sibling, CD34+ selection.
干预措施: Autologous transplantation (Other)
Risk-adapted postremission treatment
Ara-C, autologous transplantation, Allogeneic HLA-identical sibling transplantation depending on risk factors (cytogenetics, courses to CR)and availability of an HLA-identical sibling, CD34+ selection.
干预措施: Ara-C (Drug)
Risk-adapted postremission treatment
Ara-C, autologous transplantation, Allogeneic HLA-identical sibling transplantation depending on risk factors (cytogenetics, courses to CR)and availability of an HLA-identical sibling, CD34+ selection.
干预措施: Allogeneic HLA-identical sibling transplantation (Other)
Risk-adapted postremission treatment
Ara-C, autologous transplantation, Allogeneic HLA-identical sibling transplantation depending on risk factors (cytogenetics, courses to CR)and availability of an HLA-identical sibling, CD34+ selection.
干预措施: CD34+ selection (Other)
结局指标
主要结局
Complete remission rate.
时间窗: 2 months.
Analyze the efficacy and toxicity of IDICE (idarubicin, intermediate doses of ara-C and etoposide) to achieve complete remission.
Disease free survival.
时间窗: 4 years.
Analyze the disease free survival (DFS)of patients in remission, with a therapeutic strategy adjusted to the prognostic factors.
次要结局
- Evaluations of minimal residual disease (MRD) by flow cytometry during and after treatment.(4 years.)
- Feasibility to mobilize and collect autologous PBSC after consolidation phase.(6 months.)
- Evaluations of the CD34+ cell selection procedure and allogeneic peripheral blood stem cell (PBSC)transplantation outcome.(4 years.)