Risk-stratified treatment of sonrotoclax with chemotherapy in newly diagnosed acute myeloid leukemia: a study protocol
Creators: name: Zhang, Yunxiang
name: Wu, Min
name: Jin, Zhen
name: Yang, Li
name: Huang, Xufei
name: Li, Weiming
name: Zhu, Hongming
name: Wang, Wenfang
name: Chen, Qiusheng
name: Liu, Ligen
name: Chen, Zhichao
name: Wang, Shaoyuan
name: Li, Junmin
Publisher: name: Taylor & Francis
Year: 2025
Subjects: subject: Pharmacology
subject: Biotechnology
subject: Environmental Sciences not elsewhere classified
subject: Information Systems not elsewhere classified
subject: Cancer
subject: Hematology
subject: Infectious Diseases
subject: FOS: Health sciences

description: Acute myeloid leukemia (AML) treatment relied on anthracyclines and cytarabine based intensive chemotherapy. However, clinical outcomes are unsatisfied for patients with intermediate/adverse cytogenetics based on European Leukemia Net (ELN) risk stratification 2022 (ELN 2022), and relapses also remain common even in patients with favorable-risk cytogenetics with measurable residual disease (MRD). There is an urgent unmet need for optimizing intensive chemotherapy regimens with novel agents, to enhance the MRD-negative rate, achieve durable remission, and improve the prognosis of AML. Preliminary results showed that adding a B-cell lymphoma-2 (BCL-2) inhibitor to intensive chemotherapy could improve treatment efficacy. Sonrotoclax is a potent, selective, next-generation BCL-2 inhibitor that effectively inhibits both the wide-type BCL-2 and several BCL-2 mutants. We hypothesize that the addition of sonrotoclax to intensive chemotherapy may enhance the treatment efficacy for AML without untoward toxicity. Here, we describe the rationale and design of a single-arm, multicenter, phase 2 study evaluating the efficacy and safety of sonrotoclax combined with chemotherapy as an induction therapy in newly diagnosed patients with AML who are fit for intensive chemotherapy, followed by stratified subsequent consolidation and maintenance treatment based on patients’ ELN2022 at diagnosis and MRD results after induction. <b>Clinical Trail Registration</b>: NCT06497062 This study protocol evaluates the efficacy and safety of sonrotoclax combined with chemotherapy as a first-line treatment for newly diagnosed patients with acute myeloid leukemia (AML), who are fit for intensive chemotherapy. Following this first treatment phase, patients will receive different subsequent treatment based on their European Leukemia Net 2022 risk at the diagnosis of AML. The study aims at achieving a permanent disappearance of leukemia and preventing it from occurring again. The primary goal of this study is to define the proportion of patients who remain event-free at 2 years from the start of treatment, including treatment failure, disease recurrence, or death from any cause. Secondary goal includes measuring how many patients achieve complete response (have no signs of disease after treatment) and how many have no detectable remaining leukemic cells (very low or undetectable level of blast). Additionally, the study will also track how long patients remain disease-free, overall survival after two years, and the number of deaths within 30 and 60 days of treatment. Safety and potential side effects will also be closely monitored.