HAV Versus DAV/IAV Induction Regimen in Elderly Patients With Acute Myeloid Leukemia Suitable for Intensive Chemotherapy: a Multicenter, Randomized, Controlled Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- Event-free survival (EFS)
研究概览
简要总结
Acute myeloid leukemia (AML) is the most common leukemia in China, with a high incidence in elderly patients (≥60 years), who comprise over half of all cases (median age ~68 years). Elderly AML patients have a poor prognosis and carry multiple high-risk factors, with a 5-year overall survival (OS) of only 3-8%.
Before the era of novel targeted agents, the classic "3+7" regimen was the standard intensive chemotherapy for eligible elderly patients, yielding an induction complete remission (CR) rate of 40-60%. Long-term survival remained poor, as most elderly patients are not candidates for allogeneic hematopoietic stem cell transplantation.
Recent clinical studies have shown that combinations of novel targeted agents with hypomethylating agents improve outcomes in elderly or unfit patients. In a previously initiated multicenter, prospective, randomized controlled trial (NCT06066242), the investigators aimed to identify the optimal induction regimen for elderly fit patients with newly diagnosed AML. Preliminary data indicate that the DNR/IDA + Ara-C + venetoclax (DAV/IAV) regimen achieved a higher induction remission rate (77.3%) compared with DA/IA (3+7) or Ven + azacitidine (45-59%). However, this rate remains below that observed in younger adults (>85%), highlighting the need for further optimization.
详细描述
This study is a multicenter, prospective, randomized, and controlled clinical trial, which intends to enroll elderly patients diagnosed with AML in accordance with the WHO (2022) or ICC standards and are suitable for intensive chemotherapy. For patients meeting the inclusion and not meeting the exclusion criteria, they will be randomly grouped and respectively receive induction therapy with either DAV/IAV (2 + 5) or HAV regimens. Patients achieving CR/CRi/CRh after induction treatment will undergo consolidation with the intermediate-dose cytarabine regimen for two courses.After completing the induction and consolidation therapy, maintenance therapy with the VA regimen for six courses will be administered; subsequently, follow-up will be conducted. Patients in the high-risk group and those with non-negative MRD are recommended to undergo allogeneic hematopoietic stem cell transplantation.
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
- 60 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Conforming to the diagnostic criteria of AML or MDS/AML by WHO (2022) or ICC.
- •Age ≥ 60 years and ≤ 75 years, regardless of gender.
- •The performance status assessment of the Eastern Cooperative Oncology Group (ECOG-PS) is 0 -
- •Meeting the requirements of the following laboratory examination indicators (performed within 7 days before treatment):
- •1) Total bilirubin ≤ 1.5 times the upper limit of normal for the same age group; 2) AST and ALT ≤ 2.5 times the upper limit of normal for the same age group; 3) Serum creatinine < 2 times the upper limit of normal for the same age group; 4) Cardiac enzymes < 2 times the upper limit of normal for the same age group; 5) The cardiac ejection fraction determined by echocardiography (ECHO) > 50%. The informed consent form must be signed before the initiation of all specific research procedures. It should be signed by the patient himself/herself or an immediate family member. Considering the patient's condition, if the patient's signature is not conducive to the treatment of the disease, the informed consent form should be signed by the legal guardian or an immediate family member of the patient.
排除标准
- •Acute promyelocytic leukemia accompanied by the PML-RARA fusion gene
- •Acute myeloid leukemia accompanied by the RUNX1-RUNX1T1 or CBFB-MYH11 fusion gene
- •Acute myeloid leukemia accompanied by the BCR-ABL fusion gene
- •Retreated patients (referring to those who have previously undergone induction chemotherapy but can receive hydroxyurea for cytoreduction).
- •Patients concurrently suffering from malignant tumors in other organs (requiring treatment).
- •Active cardiac diseases, defined as one or more of the following:
- •1) Uncontrolled or symptomatic angina pectoris history; 2) Myocardial infarction less than 6 months from the time of enrollment in the study; 3) History of arrhythmias requiring drug treatment or with severe clinical symptoms; 4) Uncontrolled or symptomatic congestive heart failure (> NYHA Grade 2);
- •7. Severe infectious diseases (untreated tuberculosis, pulmonary aspergillosis).
- •8. Those considered ineligible for enrollment by the researcher.
研究组 & 干预措施
DAV/IAV
Induction therapy:
Ara-C 100mg/m2/d, d1-5 Daunorubicin 60mg/m2/d, d1-2 or Idarubicin 10mg/m2/d, d1-2 Venetoclax 100mg d3, 200mg d4,400mg d5-11 If the treatment achieves CR/CRi/CRh, proceed directly to consolidation therapy.
If the treatment does not achieve CR/CRi/CRh, enter the second induction phase with a different treatment regimen.
Second Induction Phase:
For patients with FLT3 or IDH1 mutations, targeted therapy can be chosen. If there is no FLT3 or IDH1 mutation or the patient is unwilling to use FLT3 or IDH1 inhibitors, switch to the HAV induction regimen.
Consolidation therapy:
- intermediate-dose Ara-C (ID-Ara-C): 2 cycles are used. Ara-C 1 g/m2/q12h on days 1, 3, and 5 (for patients aged 60-70 years) or Ara-C 500 mg/m2/q12h on days 1, 3, and 5 (for patients aged 70 years or older)
Maintenance therapy:
VA regimen: 6 courses Azacitidine 75 mg/m2/d on days 1-5, Venetoclax 400 mg on days 1-7.
干预措施: daunorubicin (Drug)
DAV/IAV
Induction therapy:
Ara-C 100mg/m2/d, d1-5 Daunorubicin 60mg/m2/d, d1-2 or Idarubicin 10mg/m2/d, d1-2 Venetoclax 100mg d3, 200mg d4,400mg d5-11 If the treatment achieves CR/CRi/CRh, proceed directly to consolidation therapy.
If the treatment does not achieve CR/CRi/CRh, enter the second induction phase with a different treatment regimen.
Second Induction Phase:
For patients with FLT3 or IDH1 mutations, targeted therapy can be chosen. If there is no FLT3 or IDH1 mutation or the patient is unwilling to use FLT3 or IDH1 inhibitors, switch to the HAV induction regimen.
Consolidation therapy:
- intermediate-dose Ara-C (ID-Ara-C): 2 cycles are used. Ara-C 1 g/m2/q12h on days 1, 3, and 5 (for patients aged 60-70 years) or Ara-C 500 mg/m2/q12h on days 1, 3, and 5 (for patients aged 70 years or older)
Maintenance therapy:
VA regimen: 6 courses Azacitidine 75 mg/m2/d on days 1-5, Venetoclax 400 mg on days 1-7.
干预措施: Venetoclax (Drug)
DAV/IAV
Induction therapy:
Ara-C 100mg/m2/d, d1-5 Daunorubicin 60mg/m2/d, d1-2 or Idarubicin 10mg/m2/d, d1-2 Venetoclax 100mg d3, 200mg d4,400mg d5-11 If the treatment achieves CR/CRi/CRh, proceed directly to consolidation therapy.
If the treatment does not achieve CR/CRi/CRh, enter the second induction phase with a different treatment regimen.
Second Induction Phase:
For patients with FLT3 or IDH1 mutations, targeted therapy can be chosen. If there is no FLT3 or IDH1 mutation or the patient is unwilling to use FLT3 or IDH1 inhibitors, switch to the HAV induction regimen.
Consolidation therapy:
- intermediate-dose Ara-C (ID-Ara-C): 2 cycles are used. Ara-C 1 g/m2/q12h on days 1, 3, and 5 (for patients aged 60-70 years) or Ara-C 500 mg/m2/q12h on days 1, 3, and 5 (for patients aged 70 years or older)
Maintenance therapy:
VA regimen: 6 courses Azacitidine 75 mg/m2/d on days 1-5, Venetoclax 400 mg on days 1-7.
干预措施: cytarabine (Drug)
DAV/IAV
Induction therapy:
Ara-C 100mg/m2/d, d1-5 Daunorubicin 60mg/m2/d, d1-2 or Idarubicin 10mg/m2/d, d1-2 Venetoclax 100mg d3, 200mg d4,400mg d5-11 If the treatment achieves CR/CRi/CRh, proceed directly to consolidation therapy.
If the treatment does not achieve CR/CRi/CRh, enter the second induction phase with a different treatment regimen.
Second Induction Phase:
For patients with FLT3 or IDH1 mutations, targeted therapy can be chosen. If there is no FLT3 or IDH1 mutation or the patient is unwilling to use FLT3 or IDH1 inhibitors, switch to the HAV induction regimen.
Consolidation therapy:
- intermediate-dose Ara-C (ID-Ara-C): 2 cycles are used. Ara-C 1 g/m2/q12h on days 1, 3, and 5 (for patients aged 60-70 years) or Ara-C 500 mg/m2/q12h on days 1, 3, and 5 (for patients aged 70 years or older)
Maintenance therapy:
VA regimen: 6 courses Azacitidine 75 mg/m2/d on days 1-5, Venetoclax 400 mg on days 1-7.
干预措施: azacitidine (Drug)
DAV/IAV
Induction therapy:
Ara-C 100mg/m2/d, d1-5 Daunorubicin 60mg/m2/d, d1-2 or Idarubicin 10mg/m2/d, d1-2 Venetoclax 100mg d3, 200mg d4,400mg d5-11 If the treatment achieves CR/CRi/CRh, proceed directly to consolidation therapy.
If the treatment does not achieve CR/CRi/CRh, enter the second induction phase with a different treatment regimen.
Second Induction Phase:
For patients with FLT3 or IDH1 mutations, targeted therapy can be chosen. If there is no FLT3 or IDH1 mutation or the patient is unwilling to use FLT3 or IDH1 inhibitors, switch to the HAV induction regimen.
Consolidation therapy:
- intermediate-dose Ara-C (ID-Ara-C): 2 cycles are used. Ara-C 1 g/m2/q12h on days 1, 3, and 5 (for patients aged 60-70 years) or Ara-C 500 mg/m2/q12h on days 1, 3, and 5 (for patients aged 70 years or older)
Maintenance therapy:
VA regimen: 6 courses Azacitidine 75 mg/m2/d on days 1-5, Venetoclax 400 mg on days 1-7.
干预措施: Idarubicin (Drug)
HAV
Induction Therapy:
Ara-C 100mg/m2/d, d1-5 HHT 2mg/m2/d, d1-5 Venetoclax 100mg d3, 200mg d4,400mg d5-11 If CR/CRi/CRh is achieved, proceed directly to consolidation therapy. If the treatment does not reach CR/CRi/CRh, enter the second induction phase with a different treatment regimen.
Second course:
For patients with FLT3 or IDH1 mutations, the corresponding targeted therapy can be selected, as before.
For patients without FLT3 or IDH1 mutations or those who do not want to use FLT3 or IDH1 inhibitors, the DAV/IAV induction regimen is changed.
If the treatment does not reach CR/CRi/CRh after two courses, the patient is discharged.
Consolidation therapy:
- intermediate-dose Ara-C (ID-Ara-C): 2 cycles are used. Ara-C 1 g/m2/q12h on days 1, 3, and 5 (for patients aged 60-70 years) or Ara-C 500 mg/m2/q12h on days 1, 3, and 5 (for patients aged 70 years or older)
Maintenance therapy:
VA : 6 courses
干预措施: Venetoclax (Drug)
HAV
Induction Therapy:
Ara-C 100mg/m2/d, d1-5 HHT 2mg/m2/d, d1-5 Venetoclax 100mg d3, 200mg d4,400mg d5-11 If CR/CRi/CRh is achieved, proceed directly to consolidation therapy. If the treatment does not reach CR/CRi/CRh, enter the second induction phase with a different treatment regimen.
Second course:
For patients with FLT3 or IDH1 mutations, the corresponding targeted therapy can be selected, as before.
For patients without FLT3 or IDH1 mutations or those who do not want to use FLT3 or IDH1 inhibitors, the DAV/IAV induction regimen is changed.
If the treatment does not reach CR/CRi/CRh after two courses, the patient is discharged.
Consolidation therapy:
- intermediate-dose Ara-C (ID-Ara-C): 2 cycles are used. Ara-C 1 g/m2/q12h on days 1, 3, and 5 (for patients aged 60-70 years) or Ara-C 500 mg/m2/q12h on days 1, 3, and 5 (for patients aged 70 years or older)
Maintenance therapy:
VA : 6 courses
干预措施: cytarabine (Drug)
HAV
Induction Therapy:
Ara-C 100mg/m2/d, d1-5 HHT 2mg/m2/d, d1-5 Venetoclax 100mg d3, 200mg d4,400mg d5-11 If CR/CRi/CRh is achieved, proceed directly to consolidation therapy. If the treatment does not reach CR/CRi/CRh, enter the second induction phase with a different treatment regimen.
Second course:
For patients with FLT3 or IDH1 mutations, the corresponding targeted therapy can be selected, as before.
For patients without FLT3 or IDH1 mutations or those who do not want to use FLT3 or IDH1 inhibitors, the DAV/IAV induction regimen is changed.
If the treatment does not reach CR/CRi/CRh after two courses, the patient is discharged.
Consolidation therapy:
- intermediate-dose Ara-C (ID-Ara-C): 2 cycles are used. Ara-C 1 g/m2/q12h on days 1, 3, and 5 (for patients aged 60-70 years) or Ara-C 500 mg/m2/q12h on days 1, 3, and 5 (for patients aged 70 years or older)
Maintenance therapy:
VA : 6 courses
干预措施: azacitidine (Drug)
HAV
Induction Therapy:
Ara-C 100mg/m2/d, d1-5 HHT 2mg/m2/d, d1-5 Venetoclax 100mg d3, 200mg d4,400mg d5-11 If CR/CRi/CRh is achieved, proceed directly to consolidation therapy. If the treatment does not reach CR/CRi/CRh, enter the second induction phase with a different treatment regimen.
Second course:
For patients with FLT3 or IDH1 mutations, the corresponding targeted therapy can be selected, as before.
For patients without FLT3 or IDH1 mutations or those who do not want to use FLT3 or IDH1 inhibitors, the DAV/IAV induction regimen is changed.
If the treatment does not reach CR/CRi/CRh after two courses, the patient is discharged.
Consolidation therapy:
- intermediate-dose Ara-C (ID-Ara-C): 2 cycles are used. Ara-C 1 g/m2/q12h on days 1, 3, and 5 (for patients aged 60-70 years) or Ara-C 500 mg/m2/q12h on days 1, 3, and 5 (for patients aged 70 years or older)
Maintenance therapy:
VA : 6 courses
干预措施: Homoharringtonine (Drug)
结局指标
主要结局
Event-free survival (EFS)
时间窗: Up to approximately 1 years after the date of the last enrolled participants
It is defined as the time from the start of randomization to the occurrence of induction failure or disease progression or death from any cause (whichever occurs first)
次要结局
- Complete remission (CR) rate or complete remission with partial hematologic recovery (CRh) rate or complete remission with incomplete hematologic recovery (CRi) rate(Up to approximately eight weeks afer induction therapy)
- Undectable Minimal residual disease (MRD) by flow cytometry compelete remission rates after induction(Up to approximately eight weeks afer induction therapy)
- Undectable Minimal residual disease (MRD) by flow cytometry complete remission rates in the whole treatment(up to 1 years after the date of the last enrolled participants)
- Relapse-free Survival (RFS)(Up to approximately 1 years after the date of the last enrolled participants)
- 30-day postinduction mortality(Up to approximately 30 days)
- 60-day postinduction mortality(Up to approximately 60 days)
- overall survival(up to 1 years after the date of the last enrolled participants)