AML
Conditions
Keywords
Elderly Patients
Brief summary
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.
Interventions
DRUGdaunorubicin
Used in combination with cytarabine and venetoclax for induction therapy in DAV.
DRUGVenetoclax
Used in combination with cytarabine and daunorubicin for induction therapy in DAV.
DRUGcytarabine
Used in combination with venetoclax and daunorubicin for induction therapy in DAV or used by intermediate does for consolidation therapy.
DRUGazacitidine
Used in combination with venetoclax for maintenance therapy.
Used in combination with cytarabine and venetoclax for induction therapy in HAV.
DRUGIdarubicin
Used in combination with cytarabine and venetoclax for induction therapy in IAV.
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Conforming to the diagnostic criteria of AML or MDS/AML by WHO (2022) or ICC. 2. Age ≥ 60 years and ≤ 75 years, regardless of gender. 3. The performance status assessment of the Eastern Cooperative Oncology Group (ECOG-PS) is 0 - 2. 4. 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.
Exclusion criteria
1. Acute promyelocytic leukemia accompanied by the PML-RARA fusion gene 2. Acute myeloid leukemia accompanied by the RUNX1-RUNX1T1 or CBFB-MYH11 fusion gene 3. Acute myeloid leukemia accompanied by the BCR-ABL fusion gene 4. Retreated patients (referring to those who have previously undergone induction chemotherapy but can receive hydroxyurea for cytoreduction). 5. Patients concurrently suffering from malignant tumors in other organs (requiring treatment). 6. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-free survival (EFS) | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Proportion of patients with CR, CRh or CRi |
| Undectable Minimal residual disease (MRD) by flow cytometry compelete remission rates after induction | Up to approximately eight weeks afer induction therapy | Among those who have achieved CR/CRh/CRi after induction, proportion of patients who is undectable MRD by flow cytometry |
| 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 | Among those who have achieved CR/CRh/CRi in the whole treatment, proportion of patients who is undectable MRD by flow cytometry |
| Relapse-free Survival (RFS) | Up to approximately 1 years after the date of the last enrolled participants | It is defined as the time from the start of achieving remission to disease progression, death from any cause or the last follow-up. |
| 30-day postinduction mortality | Up to approximately 30 days | It is defined as death from any cause within 30 days after the start of induction. |
| 60-day postinduction mortality | Up to approximately 60 days | It is defined as death from any cause within 60 days after the start of induction. |
| overall survival | up to 1 years after the date of the last enrolled participants | The interval from the date of enrollment to the date of death or the date of last follow-up, whichever occurred first. |
Countries
China
Outcome results
None listed