MRD-positive AML: a Prospective, Single-arm, Multicenter Platform Clinical Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 537
- 试验地点
- 2
- 主要终点
- relapse-free survival rate
研究概览
简要总结
This clinical trial is a platform-type clinical study intended to investigate the efficacy and safety of MRD-positive acute myeloid leukemia patients after comprehensive treatment, which includes but is not limited to the following drugs and protocols: Chemotherapy, small molecule targeted drugs, demethylation drugs, liposome drugs and the combination of these drugs to form a combination of treatment regimen, the specific treatment regimen will be updated according to the results of this trial and the latest research progress at home and abroad.
详细描述
Patients aged 14 years or older with diagnosed AML (non-M3) who have achieved complete remission in bone marrow morphology but are positive for minimal residual disease by flow cytometry or have the following genetic mutations that can be detected by PCR: NPM1 mutation, IDH1/2 mutation, DEK-NUP214 (DEK-CAN), RUNX1-RUNX1T1(AML 1-ETO), or CBFβ-MYH 11[4]. NGS can detect mutations such as FLT3.
For eligible patients, the treatment plan is selected by the doctor in charge according to the specific conditions of the patient. During the treatment, patients can have hematopoietic stem cell transplantation at any time.
This study compared relapse-free survival and overall survival of MRD-positive patients after effective and persistent MRD treatment, and based on the results, observed the efficacy and safety of different treatment regiments for MRD-positive AML patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 14 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •AML (non-M3) compliant with WHO (2016) standards;
- •In morphological complete remission.
- •Mrd-positive patients: including bone marrow flow cytometry, PCR quantification of NPM1 mutations, PCR quantification of fusion genes (RUNX 1-RUNX1T1, CBFB-MYH11 and DEK-NUP214), or NGS detection of FLT3 mutation positive.
- •Age over 14 years old, male or female. Informed consent must be signed prior to the commencement of all specific study procedures, and for those 14 years of age and older, informed consent must be signed by the patient or an immediate family member. Considering the patient's condition, if the patient's signature is not conducive to the treatment of the condition, the informed consent shall be signed by the legal guardian or the patient's immediate family.
排除标准
- •Patients who intend to undergo hematopoietic stem cell transplantation within 4 weeks
- •The diagnosis is APL
- •Those who were not considered suitable for inclusion by the researchers.
研究组 & 干预措施
With lDH1 gene mutation
Ivosidenib 500mg/d: d1-28 ；Azacitidine 75mg/m2/d: d1-7；Venetoclax 600mg/d: d1-14
干预措施: Azacitidine (Drug)
Daunorubicin/Mitoxantrone/Idarubicin+Cytarabine +Venetoclax
Cytarabine 100mg/m2/d, d1-5； Daunorubicin 45mg/m2/d，d1-2； or Idarubicin 10mg/ m2/d，d1-2； or Mitoxantrone 8mg/ m2/d d1-2; Venetoclax 400mg d1-7
干预措施: Idarubicin (Drug)
c-kit mutation
Avapritinib 200mg/ day, 28 days a course; Azacitidine 75mg/m2/d: d1-7
干预措施: Azacitidine (Drug)
Cytarabine+Homoharringtonine+Venetoclax
Cytarabine 100mg/ m2/d, d1-5; Homoharringtonine 2mg/ m2 d1-5; Venetoclax 400mg d1-7
干预措施: Homoharringtonine (Drug)
Daunorubicin/Mitoxantrone/Idarubicin+Cytarabine +Venetoclax
Cytarabine 100mg/m2/d, d1-5； Daunorubicin 45mg/m2/d，d1-2； or Idarubicin 10mg/ m2/d，d1-2； or Mitoxantrone 8mg/ m2/d d1-2; Venetoclax 400mg d1-7
干预措施: Venetoclax (Drug)
NPM1 mutation or IDH2 mutation
Azacitidine 75mg/m2/d: d1-7；Venetoclax400mg/d: d1-21 or Cytarabine 20mg/m2/d : d1-10；Venetoclax 600mg/d: d1-21
干预措施: Cytarabine (Drug)
N-RAS and NF1 mutations
Azacitidine 75 mg/m² on days 1-7 Tunlametinib 12 mg twice daily, 28-day cycle
干预措施: Azacitidine (Drug)
NPM1 mutation or IDH2 mutation
Azacitidine 75mg/m2/d: d1-7；Venetoclax400mg/d: d1-21 or Cytarabine 20mg/m2/d : d1-10；Venetoclax 600mg/d: d1-21
干预措施: Azacitidine (Drug)
Cytarabine+Homoharringtonine+Venetoclax
Cytarabine 100mg/ m2/d, d1-5; Homoharringtonine 2mg/ m2 d1-5; Venetoclax 400mg d1-7
干预措施: Venetoclax (Drug)
Daunorubicin/Mitoxantrone/Idarubicin+Cytarabine +Venetoclax
Cytarabine 100mg/m2/d, d1-5； Daunorubicin 45mg/m2/d，d1-2； or Idarubicin 10mg/ m2/d，d1-2； or Mitoxantrone 8mg/ m2/d d1-2; Venetoclax 400mg d1-7
干预措施: Daunorubicin (Drug)
With lDH1 gene mutation
Ivosidenib 500mg/d: d1-28 ；Azacitidine 75mg/m2/d: d1-7；Venetoclax 600mg/d: d1-14
干预措施: Ivosidenib (Drug)
N-RAS and NF1 mutations
Azacitidine 75 mg/m² on days 1-7 Tunlametinib 12 mg twice daily, 28-day cycle
干预措施: Trametinib (Drug)
c-kit mutation
Avapritinib 200mg/ day, 28 days a course; Azacitidine 75mg/m2/d: d1-7
干预措施: Avapritinib (Drug)
FLT3 gene mutation
Gilteritinilb 120mg/d: d1-28； Venetocax 400mg/d: d1-7；Azacitidine 75mg/m2/d : d1-7
干预措施: Azacitidine (Drug)
With lDH1 gene mutation
Ivosidenib 500mg/d: d1-28 ；Azacitidine 75mg/m2/d: d1-7；Venetoclax 600mg/d: d1-14
干预措施: Venetoclax (Drug)
Venetoclax+Azacitidine/Venetoclax+Cytarabine
Azacitidine75 mg/m2 day1-7；Venetoclax 400mg day1-21 or，Cytarabine 20mg/m2 /day，day1-10； Venetoclax 600mg day1-21
干预措施: Venetoclax (Drug)
Cytarabine+Homoharringtonine+Venetoclax
Cytarabine 100mg/ m2/d, d1-5; Homoharringtonine 2mg/ m2 d1-5; Venetoclax 400mg d1-7
干预措施: Cytarabine (Drug)
NPM1 mutation or IDH2 mutation
Azacitidine 75mg/m2/d: d1-7；Venetoclax400mg/d: d1-21 or Cytarabine 20mg/m2/d : d1-10；Venetoclax 600mg/d: d1-21
干预措施: Venetoclax (Drug)
JAK2 or CSF3R T618I mutation
Azacitidine 75 mg/m² on days 1-7 Ruxolitinib 20 mg twice daily, 28-day cycle
干预措施: Azacitidine (Drug)
JAK2 or CSF3R T618I mutation
Azacitidine 75 mg/m² on days 1-7 Ruxolitinib 20 mg twice daily, 28-day cycle
干预措施: Ruxolitinib (Drug)
Daunorubicin/Mitoxantrone/Idarubicin+Cytarabine +Venetoclax
Cytarabine 100mg/m2/d, d1-5； Daunorubicin 45mg/m2/d，d1-2； or Idarubicin 10mg/ m2/d，d1-2； or Mitoxantrone 8mg/ m2/d d1-2; Venetoclax 400mg d1-7
干预措施: Cytarabine (Drug)
Venetoclax+Azacitidine/Venetoclax+Cytarabine
Azacitidine75 mg/m2 day1-7；Venetoclax 400mg day1-21 or，Cytarabine 20mg/m2 /day，day1-10； Venetoclax 600mg day1-21
干预措施: Azacitidine (Drug)
Daunorubicin/Mitoxantrone/Idarubicin+Cytarabine +Venetoclax
Cytarabine 100mg/m2/d, d1-5； Daunorubicin 45mg/m2/d，d1-2； or Idarubicin 10mg/ m2/d，d1-2； or Mitoxantrone 8mg/ m2/d d1-2; Venetoclax 400mg d1-7
干预措施: Mitoxantrone (Drug)
FLT3 gene mutation
Gilteritinilb 120mg/d: d1-28； Venetocax 400mg/d: d1-7；Azacitidine 75mg/m2/d : d1-7
干预措施: Gilteritinib (Drug)
FLT3 gene mutation
Gilteritinilb 120mg/d: d1-28； Venetocax 400mg/d: d1-7；Azacitidine 75mg/m2/d : d1-7
干预措施: Venetoclax (Drug)
Venetoclax+Azacitidine/Venetoclax+Cytarabine
Azacitidine75 mg/m2 day1-7；Venetoclax 400mg day1-21 or，Cytarabine 20mg/m2 /day，day1-10； Venetoclax 600mg day1-21
干预措施: Cytarabine (Drug)
结局指标
主要结局
relapse-free survival rate
时间窗: up to 6 months
次要结局
- Measurable Residual Disease(up to 6 months)
- The incidence of adverse events such as serious infections during treatment(up to 2 years)
- Proportion of MRD turning negative(up to 6 months)
- Overall survival(OS ) rate(From the time the patients participated in the clinical trial until the patient died)
- Adverse Events (AEs)(up to 2 years)
- Cumulative relapse rate(From the time the patients participated in the clinical trial until the patient relapsed)