Risk Adapted Treatment for Primary AML in Adults, Based on Genetics and Minimal Residual Disease (MRD) in Patients up to the Age of 70 Years.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 862
- 试验地点
- 21
- 主要终点
- Complete remission rate (CRR)
研究概览
简要总结
The AML-03 regimen investigates the addition of G-CSF priming to both induction and consolidation chemotherapies administrated in the previous AML-99 trial (NCT01716793) refines risk-stratification based on biological characterization also the AML-03 trial incorporates novel approaches for hematopoietic stem cell transplantation: such as Mylotarg™ "in vivo purging" in autografts, extends unrelated volunteers donors for allotransplants in high-risk patients, and introduces reduced intensity conditioning in patients with elder age (more than 50 years old).
The aims of these modifications are to analyse eficacy and toxicity of this induction and consolidation therapy and to analyse the disease free survival in patients who achieved complete response following a risk adjusted therapy.
详细描述
Induction chemotherapy: idarubicin (12mg/m2/day intravenous, days 1, 3 and 5), intermediate-dose cytarabine (500mg/m2/12h, intravenous, days 1, 3 and 5) and etoposide (100mg/m2/day, intravenous, from day 1 to 3) as in AML-99 trial (NCT01716793), with the addition of subcutaneous G-CSF from day 0 to the last day of chemotherapy. This induction therapy is repeated if complete remission (CR) is not achieved after the first course of treatment.
Consolidation therapy (as in AML-99 trial): mitoxantrone (12mg/m2/day, intravenous, days 4 to 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)] and Leukocyte index <20 at diagnosis (LI=white blood cell count (WBC) x (blasts in bone marrow/100) are treated with one course of high-dose cytarabine (3g/m2/12h, intravenous, days 1, 3 and 5), but in case of LI>20 at diagnosis the intention is to perform an autologous peripheral blood stem cell (PBSC) transplantation.
- Patients in intermediate risk group, with normal karyotype, a single course of induction chemotherapy to achieve the CR, the absence of adverse molecular features (FLT3-ITD or MLL-PTD) and low minimal residual disease levels after consolidation (MRD<0,1%) receive an autologous PBSC transplant, regardless of having an HLA-identical sibling.
- The remaining patients defined as high-risk patients are treated with an allogeneic stem cell transplantation. Depending on the age, if the patient has an HLA-identical sibling donor, up to age of 50 years old it is performed with conventional conditioning therapy and positive selection of CD34+, older patients receive a reduced intensity conditioning regimen.
- Very high risk patients without a sibling are allocated to unrelated donor (9-10/10). Patients with adverse cytogenetics and/or FLT3-ITD without an adequate donor received Mylotarg™ as "in vivo purging" followed by an autologous PBSC transplantation.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with newly diagnosed AML, classified using OMS criteria.
- •Patients with 70 years old or younger.
排除标准
- •Patients previously treated for the AML with chemotherapy different from hidroxiurea.
- •Acute promyelocytic leukemia with t(15;17).
- •Cronic mieloid leukemia in blastic crisis.
- •Leukemias that appear after other myeloproliferative processes.
- •Leukemias that survive after myelodysplasic syndromes of more than 6 months of evolution.
- •Presence of other neoplasic disease in activity.
- •Secondary AML which appears after cured malignant disease (for instance, Hodgking disease), and those who are still exposed to alkilant agents or radiation.
- •Abnormal renal and hepatic functions with creatinin and/or bilirrubine 2 times higher than the normal threshold, except when the alteration should be attributed to the leukemia.
- •Patient with an ejection fraction below 40%, symptomatic cardiac deficiency or both.
- •Patients with neurological or concomitant psychiatric disease.
- •Positivity by HIV.
研究组 & 干预措施
Risk-adapted postremission treatment.
Ara-C, G-CSF, Autologous peripheral blood stem cell transplantation, Allogeneic matched related or unrelated donor transplant, G-CSF Priming, CD34+ selection, Myeloablative or reduced intensity conditioning, Mylotarg purging before autologous PBSC transplantation.
干预措施: Ara-C (Drug)
Risk-adapted postremission treatment.
Ara-C, G-CSF, Autologous peripheral blood stem cell transplantation, Allogeneic matched related or unrelated donor transplant, G-CSF Priming, CD34+ selection, Myeloablative or reduced intensity conditioning, Mylotarg purging before autologous PBSC transplantation.
干预措施: Autologous peripheral blood stem cell transplantation. (Other)
Risk-adapted postremission treatment.
Ara-C, G-CSF, Autologous peripheral blood stem cell transplantation, Allogeneic matched related or unrelated donor transplant, G-CSF Priming, CD34+ selection, Myeloablative or reduced intensity conditioning, Mylotarg purging before autologous PBSC transplantation.
干预措施: Allogeneic matched related or unrelated donor transplant. (Other)
Risk-adapted postremission treatment.
Ara-C, G-CSF, Autologous peripheral blood stem cell transplantation, Allogeneic matched related or unrelated donor transplant, G-CSF Priming, CD34+ selection, Myeloablative or reduced intensity conditioning, Mylotarg purging before autologous PBSC transplantation.
干预措施: G-CSF (Drug)
Risk-adapted postremission treatment.
Ara-C, G-CSF, Autologous peripheral blood stem cell transplantation, Allogeneic matched related or unrelated donor transplant, G-CSF Priming, CD34+ selection, Myeloablative or reduced intensity conditioning, Mylotarg purging before autologous PBSC transplantation.
干预措施: CD34+ selection. (Other)
Risk-adapted postremission treatment.
Ara-C, G-CSF, Autologous peripheral blood stem cell transplantation, Allogeneic matched related or unrelated donor transplant, G-CSF Priming, CD34+ selection, Myeloablative or reduced intensity conditioning, Mylotarg purging before autologous PBSC transplantation.
干预措施: Mylotarg purging before autologous PBSC transplantation (Other)
结局指标
主要结局
Complete remission rate (CRR)
时间窗: 2 months.
Analyze the efficacy and toxicity of IDICE-G (idarubicin, intermediate doses of ara-C and etoposide) and G-CSF to achieve complete remission.
Disease free survival (DFS).
时间窗: 4 years.
Analyze the disease free suvival of patients in remission, with a therapeutic strategy adjusted to the prognostic factors. Mortality in remission after chemotherapy and/or peripheral blood stem cell tranplantation.
次要结局
- Toxicity in patients over 60 years old.(4 years.)
- Evaluation of minimal residual disease (MRD) by flow cytometry and/or molecular markers during and after treatment.(4 years.)
- Feasibility of post-remission treatment in patients with 60 or more years old.(4 years.)