Acute Myeloid Leukemia (AML)
Conditions
Brief summary
This randomized, open label, multi arm phase II trial will evaluate the efficacy and safety of venetoclax based induction regimens of varying intensity (VA, VAM, or 2+5+V) versus standard 3+7 in fit patients aged ≥14 years with newly diagnosed AML. The trial is designed to select the optimal regimen as the experimental arm for a subsequent phase III randomized controlled trial. A total of 320 patients will be enrolled in this study，and segregated into four groups with 80 in each group. Patients who achieve CR/CRi/CRh after using different induction regimens will receive the same consolidation. Allogeneic hematopoietic stem cell transplantation is recommended for patients in the high-risk group or those with persist MRD positivity. After completion of the treatment phase, patients entered the follow-up period.
Interventions
DRUGDaunorubicin
daunorubicin: 60 mg/m2, administered by intravenous drip (ivgtt) on days 1-3,
DRUGCytarabine
Cytarabine: 100 mg/m2, administered by intravenous drip (ivgtt) on days 1-7,
Liposome Mitoxantrone: 24 mg/m², administered by intravenous drip (ivgtt) on day 1,
DRUGVenetoclax
Venetoclax: 100 mg on day 1, 200 mg on day 2, and 400 mg on days 3-14, administered orally (po),
DRUGAzacitidine
Azacitidine: 75 mg/m², administered subcutaneously (sc) on days 1-7,
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
14 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of AML per WHO (2022) or ICC criteria, and MDS/AML as defined by ICC (with bone marrow blast percentage of 10%-20%). * Age ≥14 years, male or female. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. * Judged by the investigator to be suitable for intensive induction chemotherapy and expected to tolerate the treatment intensity specified in the protocol. * Meet the following laboratory test requirements (assessed within 7 days prior to treatment): 1. Total bilirubin ≤1.5 × upper limit of normal (ULN) for the same age group; 2. AST and ALT ≤2.5 × ULN for the same age group; 3. Serum creatinine \<2 × ULN for the same age group; 4. Cardiac enzymes \<2 × ULN for the same age group; 5. Cardiac ejection fraction determined by echocardiography (ECHO) within the normal range. * Written informed consent must be signed before any study specific procedures are initiated, by the patient themselves or by their immediate family members. If, in consideration of the patient's medical condition, signing by the patient themselves would be detrimental to their treatment, the informed consent may be signed by the legally authorized representative or the patient's immediate family members.
Exclusion criteria
* Acute promyelocytic leukemia with PML-RARA fusion gene. * Acute myeloid leukemia with RUNX1-RUNX1T1 or CBFB-MYH11 fusion gene. * Acute myeloid leukemia with BCR-ABL fusion gene. * Presence of FLT3 mutation (these patients are recommended to be enrolled in clinical trials of FLT3 inhibitors). * Patients who have previously received induction chemotherapy (however, cytoreductive therapy such as hydroxyurea is permitted). * Concurrent malignancy of other organs that requires treatment. * Active cardiac disease, defined as one or more of the following: 1. History of uncontrolled or symptomatic angina pectoris; 2. Myocardial infarction within 6 months prior to study enrollment; 3. History of arrhythmia requiring medication or with clinically significant symptoms; 4. Uncontrolled or symptomatic congestive heart failure (\> NYHA class 2). * Serious infectious diseases (e.g., active tuberculosis, pulmonary aspergillosis). * Patients deemed unsuitable for enrollment by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-free survival (EFS) | up to 3 years | 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 |
|---|---|---|
| 30-day postinduction mortality | up to 30 days | It is defined as death from any cause within 30 days after the start of induction. |
| 60-day postinduction mortality | Up to 60 days | It is defined as death from any cause within 60 days after the start of induction. |
| Composite complete remission (CRc) rate | Up to eight weeks | Proportion of patients with complete remission (CR), complete remission with partial hematologic recovery (CRh) or complete remission with incomplete hematologic recovery (CRi). |
| Measurable Residual Disease (MRD) negative rate by flow cytometry | Up to eight weeks | Among those who have achieved CR/CRh/CRi after induction, proportion of patients who is MRD-negative by flow cytometry. |
| Measurable Residual Disease (MRD) negative rate by molecular testing | Up to approximately eight weeks | Among those who have achieved CR/CRh/CRi after induction, proportion of patients who is MRD-negative by molecular testing. |
| Relapse-free Survival (RFS) | Up to 3 years | It is defined as the time from the start of achieving remission to disease progression, death from any cause or the last follow-up. |
| Overall survival (OS) | Up to 3 years | It is defined as the time from the start of randomization to the death from any cause. |
| Cumulative incidence of relapse (CIR) | Up to 3 years | It is defined as the time from the start of achieving remission to hematologic relapse. |
| Incidence of treatment related adverse events | From day 1 of treatment to 28 days after the last dose | The safety of the drug was evaluated by NCI-CTC AE 5.0 standard which including hematologic and non-hematologic toxicity. |
Contacts
CONTACTHui Wei, MD
CONTACTMiao Yang, MD
Outcome results
None listed