Acute Myeloid Leukemia
Conditions
Keywords
elderly, AML, venetoclax, allo-HSCT
Brief summary
Elderly patients with acute myeloid leukemia (AML) often face unfavorable prognostic factors such as multiple comorbidities, adverse cytogenetic profiles, and pre-existing hematological disorders. The long-term survival rate remains very low, with a 5-year survival rate of only 5% to 10%. The introduction of the BCL-2 inhibitor venetoclax (Ven) has improved the induction remission rates in elderly patients. However, the question of whether to use chemotherapy maintenance or proceed with allogeneic hematopoietic stem cell transplantation (allo-HSCT) for post-remission consolidation therapy remains unclear due to the lack of prospective controlled studies. Therefore, our center plans to conduct a prospective, open-label, two-arm, non-randomized, single-center study to further explore the optimal consolidation treatment strategy for elderly AML patients at intermediate and high risk following induction complete remission (CR).
Interventions
DRUGVenetoclax
The consolidation therapy involves a regimen of intermediate-dose cytarabine (Ara-C) combined with Ven, specifically Ara-C at 1.0 g/m²/day for 3 days (days 1-3) and Ven at 400 mg/day for 10 to 14 days (days 1-10 to 14), with each cycle lasting 4 to 6 weeks, for a total of 3 consolidation cycles. This is followed by maintenance therapy with azacitidine (AZA) at 50 mg/m²/day for 5 days (days 1-5), with each cycle lasting 4 weeks, for a total of 6 maintenance cycles.
The consolidation therapy involves allo-HSCT, with the choice of conditioning regimens typically using reduced-intensity conditioning such as the Fludarabine+Busulfan (FluBu) or Fludarabine+Melphalan (FluMel) regimens commonly used by centers, which can also include Ven. FluBu regimen: Flu 30 mg/m²/day from day -10 to day -5, Bu 3.2 mg/kg/day from day -6 to day -5 or day -7 to day -5, antithymocyte globulin (ATG) (e.g., rabbit ATG at a total dose of 6-7.5 mg/kg, administered from day -4 to day -1), and Ven from day -10 to day -4. FluMel regimen: Flu 30 mg/m²/day from day -10 to day -5, Mel 50-70 mg/m²/day from day -4 to day -3, ATG and Ven from day -10 to day -4. 12 weeks (±4 weeks) post-HSCT maintenance begins with AZA at 32 mg/m²/day for 5 days (days 1-5), with each lasting 6 weeks, for a total of 6 cycles. Donor lymphocyte infusion is allowed in cases of minimal residual disease (MRD) positivity.
Sponsors
He Huang
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosed with AML according to the 2022 WHO diagnostic criteria; * Age 60-75 years; * Intermediate to high-risk AML according to the ELN criteria, AML with myelodysplasia-related changes (AML-MRC) or therapy-related AML (t-AML), or core-binding factor AML (CBF-AML) with D816 KIT mutation; or newly diagnosed hypercellular leukemia (WBC ≥ 10×10\^9/L); * Achieved CR or CR with incomplete hematologic recovery (CRi) after one to two courses of induction chemotherapy; * Have a matched related, haploidentical, or mismatched unrelated hematopoietic stem cell donor; * Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2; Creatinine clearance ≥ 60 mL/min (calculated using the Cockcroft-Gault formula); * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3× the upper limit of normal (ULN), and total bilirubin ≤ 2× ULN; * Echocardiography (ECHO) showing left ventricular ejection fraction (LVEF) ≥ 50%; Expected survival \> 8 weeks; * Voluntarily signed the informed consent form and can understand and comply with the study's requirements.
Exclusion criteria
* Currently has clinically active cardiovascular disease, such as uncontrolled arrhythmias, uncontrolled hypertension, congestive heart failure, any class 3 or 4 heart disease according to the New York Heart Association (NYHA) functional classification, or a history of myocardial infarction within 3 months before screening; * Other severe diseases that may limit the patient's participation in this trial (e.g., severe infection, renal failure); * Known human immunodeficiency virus (HIV) infection or severe viral hepatitis not controlled by medication; * Pregnant or breastfeeding women; * Unable to understand, comply with the study protocol, or unable to sign the informed consent form.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relapse-free survival | Up to 2 years | Relapse-free survival (RFS) is measured from the date of achievement of first remission until the date of hematologic relapse or death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Non-Relapsed Mortality | Up to 2 years | Non-relapsed mortality (NRM) is measured from the date of achievement of first remission until the date of death from any cause other than relapse. |
| Overall Survival | Up to 2 years | OS is measured from the date of reaching CR1 to the date of death from any cause. |
| 2-years Relapse Rate | Up to 2 years | Relapse rate is defined as relapse probability at a given time point |
Other
| Measure | Time frame | Description |
|---|---|---|
| Minimal Residual Disease (MRD) Detected by Flow Cytometry | Up to 2 years | Research on MRD involves using flow cytometry to detect residual cancer cells, with statistical methods including Kaplan-Meier survival analysis, Fine-Gray analysis and Cox regression modeling to evaluate disease remission and predict relapse risk. |
| Number of Participants With Treatment-Related Adverse Events (AEs) as Assessed by CTCAE v5.0 | Up to 2 years | Research on AE uses descriptive statistics, Kaplan-Meier survival analysis, χ² or Fisher's exact tests to assess and compare AE incidence and survival outcomes. |
Countries
China
Contacts
Primary ContactYanmin Zhao, PhD
Outcome results
None listed