Multicenter, Platform-type Clinical Study of Refractory/Recurrent Acute Myeloid Leukemia
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 458
- 试验地点
- 1
- 主要终点
- Complex response (CRc) rate (including CR and CRi)
研究概览
简要总结
To study the optimal therapeutic strategies for salvage treatment of refractory/relapsed AML, and to clarify the effectiveness and safety of various salvage treatment options. A prospective, multicenter, platform-type study was conducted to explore the overall response rate, tolerability, and survival of patients with R/R AML with different treatment regimens.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1. Patients with acute myeloid leukemia (except for acute promyelocytic leukemia) diagnosed by bone marrow cell morphology, immunology and genetics above are classified according to the French-British-American Collaboration diagnostic criteria (FAB criteria) and the World Health Organization diagnostic criteria (WHO2016 criteria).
- •2. Meet criteria for refractory/recurrent AML (except APL). The recurrence was morphological recurrence, excluding molecular recurrence. Except for simple extramedullary leukemia.
- •3. Age and gender are not limited.
- •Informed consent must be signed before the start of the study procedure, and the informed consent must be signed by the patient himself or his immediate family if he is 18 years old and above; For young patients under the age of 18, the legal guardian shall sign the informed consent. 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
- •Concurrent malignant tumors of other organs (patients requiring treatment).
- •Participants considered unsuitable for inclusion by the researchers.
研究组 & 干预措施
Arm 5
A patient with R/R AML without IDH1 or FLT3 mutation who has not been exposed to Venetoclax in the last 3 months but who is judged by the investigators to be unfit based on physical fitness and comorbidivities is unfit to enter Arm5.
Arm5: (up to 4 cycles available)
VA :
Azacytidine 75mg/m2/d d1-7; Venetoclax 100mg d1, 200mg d2, 400mg d3-21 400mg d22-28 (if the proportion of bone marrow blasts on day 21 are greater than 5%)
干预措施: Azacitidine (Drug)
Arm 4
HAV :
Cytarabine 100mg/m2/d, d1-5; Homoharringtonine 2mg/m2 d1-5; Venetoclax 100mg d3, 200mg d4, 400mg d5-11
干预措施: Venetoclax (Drug)
Arm 2
FLT3/ITD or FLT3/TKD gene mutation (up to 2 cycles available)
GVA:
Gilteritinib 80mg, d1-28 Azacitidine 75mg/m2/d d1-7 Venetoclax 100mg d1, 200mg d2, 400mg d3-14, 400mg d14-28 (if the proportion of bone marrow blasts on day 14 are greater than 5%)
干预措施: Azacitidine (Drug)
Arm 3
For R/R AML patients without IDH1 or FLT3 mutations who have not been exposed to Venecra in the last 3 months, the investigators will determine whether they are fit patients based on physical status and comorbidivities, and if they are, they can be randomly assigned to Arm3 or Arm4 DAV/IAV/MAV Cytarabine 100mg/m2/d, d1-5 Daunorubicin 60mg/m2/d, d1-2, or Idarubicin 12mg/m2/d, d1-2, or mitoxantrone 8mg/m2/d d1-2 Venetoclax 100mg d3, 200mg d4, 400mg d5-11;
干预措施: Daunorubicin/ Idarubicin /Mitoxantrone (Drug)
Arm 6
Patients with R/R AML without IDH1 or FLT3 mutations who have been exposed to Vinecra within the last 3 months may be enrolled in the exploratory protocol group based on a comprehensive assessment of local drug availability and patient status:
Arm6:
The Investigator's choice (IC) option involves a range of drugs such as clatabine, PI3K inhibitors, histone deacetylase inhibitors, celinisol, and novel liposomes.
干预措施: PI3K inhibitors, histone deacetylase inhibitors, selinexor, novel liposomal drugs, and others (Drug)
Arm 7
DAV/IAV/MAV/HAV Regimen Cytarabine 100 mg/m²/day, days 1-5 Daunorubicin 60 mg/m²/day, days 1-2, or Idarubicin 12 mg/m²/day, days 1-2, or Mitoxantrone 8 mg/m²/day, days 1-2 / Homoharringtonine 2 mg/m²/day, days 1-5 Lisatoclax 200 mg on day 3, 400 mg on day 4, 600 mg on days 5-11
干预措施: Daunorubicin/ Idarubicin /Mitoxantrone (Drug)
Arm 7
DAV/IAV/MAV/HAV Regimen Cytarabine 100 mg/m²/day, days 1-5 Daunorubicin 60 mg/m²/day, days 1-2, or Idarubicin 12 mg/m²/day, days 1-2, or Mitoxantrone 8 mg/m²/day, days 1-2 / Homoharringtonine 2 mg/m²/day, days 1-5 Lisatoclax 200 mg on day 3, 400 mg on day 4, 600 mg on days 5-11
干预措施: Cytarabine (Drug)
Arm 8
Azacitidine 75 mg/m²/day, days 1-7 Lisatoclax 200 mg on day 1, 400 mg on day 2, 600 mg on days 3-21, and 600 mg on days 22-28 (if bone marrow blast percentage on day 21 is greater than 5%)
干预措施: Azacitidine (Drug)
Arm 1
With IDH1 gene mutation(up to 2 cycles available):IVA :
Ivosidenib 500mg d1-28 Azacitidine 75mg/m2/d d1-7 Venetoclax100mg d1, 200mg d2, 400mg d3, 800mg d4-14, d14-28(If the proportion of bone marrow blasts on day 14 is greater than 5% )
干预措施: Venetoclax (Drug)
Arm 4
HAV :
Cytarabine 100mg/m2/d, d1-5; Homoharringtonine 2mg/m2 d1-5; Venetoclax 100mg d3, 200mg d4, 400mg d5-11
干预措施: Cytarabine (Drug)
Arm 3
For R/R AML patients without IDH1 or FLT3 mutations who have not been exposed to Venecra in the last 3 months, the investigators will determine whether they are fit patients based on physical status and comorbidivities, and if they are, they can be randomly assigned to Arm3 or Arm4 DAV/IAV/MAV Cytarabine 100mg/m2/d, d1-5 Daunorubicin 60mg/m2/d, d1-2, or Idarubicin 12mg/m2/d, d1-2, or mitoxantrone 8mg/m2/d d1-2 Venetoclax 100mg d3, 200mg d4, 400mg d5-11;
干预措施: Cytarabine (Drug)
Arm 4
HAV :
Cytarabine 100mg/m2/d, d1-5; Homoharringtonine 2mg/m2 d1-5; Venetoclax 100mg d3, 200mg d4, 400mg d5-11
干预措施: Homoharringtonine (Drug)
Arm 2
FLT3/ITD or FLT3/TKD gene mutation (up to 2 cycles available)
GVA:
Gilteritinib 80mg, d1-28 Azacitidine 75mg/m2/d d1-7 Venetoclax 100mg d1, 200mg d2, 400mg d3-14, 400mg d14-28 (if the proportion of bone marrow blasts on day 14 are greater than 5%)
干预措施: Venetoclax (Drug)
Arm 1
With IDH1 gene mutation(up to 2 cycles available):IVA :
Ivosidenib 500mg d1-28 Azacitidine 75mg/m2/d d1-7 Venetoclax100mg d1, 200mg d2, 400mg d3, 800mg d4-14, d14-28(If the proportion of bone marrow blasts on day 14 is greater than 5% )
干预措施: Ivosidenib (Drug)
Arm 2
FLT3/ITD or FLT3/TKD gene mutation (up to 2 cycles available)
GVA:
Gilteritinib 80mg, d1-28 Azacitidine 75mg/m2/d d1-7 Venetoclax 100mg d1, 200mg d2, 400mg d3-14, 400mg d14-28 (if the proportion of bone marrow blasts on day 14 are greater than 5%)
干预措施: Gilteritinib (Drug)
Arm 1
With IDH1 gene mutation(up to 2 cycles available):IVA :
Ivosidenib 500mg d1-28 Azacitidine 75mg/m2/d d1-7 Venetoclax100mg d1, 200mg d2, 400mg d3, 800mg d4-14, d14-28(If the proportion of bone marrow blasts on day 14 is greater than 5% )
干预措施: Azacitidine (Drug)
Arm 5
A patient with R/R AML without IDH1 or FLT3 mutation who has not been exposed to Venetoclax in the last 3 months but who is judged by the investigators to be unfit based on physical fitness and comorbidivities is unfit to enter Arm5.
Arm5: (up to 4 cycles available)
VA :
Azacytidine 75mg/m2/d d1-7; Venetoclax 100mg d1, 200mg d2, 400mg d3-21 400mg d22-28 (if the proportion of bone marrow blasts on day 21 are greater than 5%)
干预措施: Venetoclax (Drug)
Arm 3
For R/R AML patients without IDH1 or FLT3 mutations who have not been exposed to Venecra in the last 3 months, the investigators will determine whether they are fit patients based on physical status and comorbidivities, and if they are, they can be randomly assigned to Arm3 or Arm4 DAV/IAV/MAV Cytarabine 100mg/m2/d, d1-5 Daunorubicin 60mg/m2/d, d1-2, or Idarubicin 12mg/m2/d, d1-2, or mitoxantrone 8mg/m2/d d1-2 Venetoclax 100mg d3, 200mg d4, 400mg d5-11;
干预措施: Venetoclax (Drug)
Arm 7
DAV/IAV/MAV/HAV Regimen Cytarabine 100 mg/m²/day, days 1-5 Daunorubicin 60 mg/m²/day, days 1-2, or Idarubicin 12 mg/m²/day, days 1-2, or Mitoxantrone 8 mg/m²/day, days 1-2 / Homoharringtonine 2 mg/m²/day, days 1-5 Lisatoclax 200 mg on day 3, 400 mg on day 4, 600 mg on days 5-11
干预措施: Homoharringtonine (Drug)
Arm 7
DAV/IAV/MAV/HAV Regimen Cytarabine 100 mg/m²/day, days 1-5 Daunorubicin 60 mg/m²/day, days 1-2, or Idarubicin 12 mg/m²/day, days 1-2, or Mitoxantrone 8 mg/m²/day, days 1-2 / Homoharringtonine 2 mg/m²/day, days 1-5 Lisatoclax 200 mg on day 3, 400 mg on day 4, 600 mg on days 5-11
干预措施: Lisaftoclax (Drug)
Arm 8
Azacitidine 75 mg/m²/day, days 1-7 Lisatoclax 200 mg on day 1, 400 mg on day 2, 600 mg on days 3-21, and 600 mg on days 22-28 (if bone marrow blast percentage on day 21 is greater than 5%)
干预措施: Lisaftoclax (Drug)
结局指标
主要结局
Complex response (CRc) rate (including CR and CRi)
时间窗: up to 4 years
Proportion of patients with combined responses (complete and partial responses)
次要结局
- mortality associated with salvage treatment (30 days, 60 days)(Treatment within 30 days and 60 days)
- Overall survival(the whole period of the trial, up to 730 days)
- Event-free survival(the whole period of the trial, up to 730 days)
- Relapse-free survival(the whole period of the trial, up to 730 days.)
- MRD-negative complete response rate(the whole period of the trial, up to 730 days)