HAV Versus DAV/IAV Induction Regimen in Elderly Patients With Acute Myeloid Leukemia Suitable for Intensive Chemotherapy: a Multicenter, Randomized, Controlled Clinical Trial
Acute myeloid leukemia (AML) represents the most prevalent leukemia type in China. Elderly patients (≥60 years old) have a high incidence rate, accounting for over half of all AML patients, with a median age of onset approximately 68 years. Elderly AML patients have a poor prognosis and are often accompanied with multiple high-risk factors.The 5-year overall survival (OS) is only 3-8%. Before the advent of new targeted drugs, for elderly patients with newly diagnosed AML who were suitable for intensive chemotherapy, the most commonly used chemotherapy regimen remained the classic 3 + 7 regimen. However, the complete remission (CR) rate after induction was approximately 40-60%. The majority of elderly patients were not eligible for allogeneic hematopoietic stem cell transplantation, resulting in a relatively poor long-term survival for elderly AML patients . With the emergence of new targeted drugs, clinical studies both domestically and internationally have demonstrated that the combination of various targeted drugs and demethylating agents has achieved favorable efficacy in elderly/unsuitable for intensive chemotherapy patients with newly diagnosed AML, prolonging their survival. Previously, we initiated a multicenter, prospective, randomized controlled clinical study (registration number: NCT06066242). The aim was to explore the optimal induction regimen for elderly fit patients with newly diagnosed AML. Preliminary data revealed that the regimen of daunorubicin (DNR) or idarubicin (IDA) combined with cytarabine (Ara - C, DA/IA) + venetoclax (Ven, DAV/IAV) had a higher induction remission rate (77.3% )than the DA/IA 3 + 7 and Ven + azacitidine (AZA) regimens (45% - 59%). However, compared to the induction remission rate of young adult patients with newly diagnosed AML (\> 85%), further improvement is still required. Previous research data show that HHT enhances the inhibitory effect of Ara-c on DNA synthesis in tumor cells by influencing cell cycle regulation. The combination of HHT and Ven can jointly affect the apoptotic pathway and enhance cell apoptosis. Therefore, this study intends to establish a prospective, randomized controlled clinical trial to compare the induction remission rates of the HHT + Ara-c + Ven (HAV) regimen with the DAV/IAV regimen, which,based on previous data, had the highest induction remission rate .
• 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 - 2.
• 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.