Comparing the efficacy and safety of the ABC-14 regimen (Azacitidine, Venetoclax, and Chidamide) with traditional “3+7” intensive induction regimen or AB-14 regimen (Venetoclax Combined with Azacitidine) in newly diagnosed AML: Study protocol for a prospective, multicenter, randomized, open-label clinical trial

Abstract

Abstract Background Induction therapy is the first critical step in the overall treatment of Acute myeloid leukemia (AML). The “3+7” regimen remains the backbone treatment for newly diagnosed AML patients suitable for intense chemotherapy (IC) , but its efficacy, toxicity, high cost of treatment for complications and prolonged hospital stays still require improvement. The azacitidine plus venetoclax (AB) regimen has been recommended for elderly AML patients or those who are ineligible for IC treatment. However, the efficacy and safety of the AB regimen are still unsatisfactory in terms of early death and for certain leukemia subtypes, such as M5, leukemias with RUNX1, FLT3-ITD, TP53 mutations or higher MCL-1 expression. Chidamide, a novel oral histone deacetylase inhibitor, can overcome the upregulation of MCL-1 expression induced by venetoclax. It works synergistically with azacitidine and venetoclax to induce apoptosis in acute myeloid leukemia cells. Whether the Azacitidine, Venetoclax, and Chidamide (ABC) regimen can be comparable to the “3+7” or AB regimen in newly diagnosed AML induction therapy remains to be explored. Methods Based on their suitability for IC, patients with newly diagnosed AML will be stratified into unfit-AML and fit-AML. For unfit-AML arm, patients will be randomly assigned to receive either the ABC-14 or AB-14 regimen. For fit-AML arm, patients will be randomly assigned to receive either the ABC-14 or “3+7” regimen. The primary endpoint is composite complete response rate (CRc). Secondary endpoints include the measurable residual disease (MRD) negative rate, duration of remission (DoR), 1-year Relapsed-free survival (RFS) rate, 1-year overall survival (OS) rate. Exploratory endpoints include the genetic characteristics spectrum of the ABC-14 group, Length of hospital stay, Treatment costs, Blood product transfusion volume, Quality of life and apoptosis ratio.Discussion This study aims to demonstrate that ABC-14 regimen is comparable to “3+7” regimen in the induction therapy of newly diagnosed AML, while overcoming the limitations of drug resistance of AB regimen and reducing the toxicity of the traditional “3+7” regimen. To provide a alternative treatment for induction therapy of newly diagnosed AML indiscriminately.Trial registration ClinicalTrials.gov NCT06451861, Registered on 2024.06.11, https://clinicaltrials.gov/study/NCT06451861Keywords Acute myeloid leukemia, unfit-AML, fit-AML, induction therapy, Protocol