A Prospective Study of MRD-Guided, Time-Limited Therapy With Zanubrutinib Plus Sonrotoclax in Treatment-Naïve, High-Risk Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) Patients
This study is a prospective, multicenter, open-label, single-arm phase II clinical trial evaluating the efficacy and safety of an MRD-guided, time-limited therapy with zanubrutinib combined with sonrotoclax in previously untreated high-risk CLL/SLL patients.
• Patients must meet all of the following inclusion criteria to be enrolled in this study:
‣ Age between 18 and 75 years, inclusive. Diagnosis of CLL/SLL according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria.
‣ Meeting iwCLL 2018 treatment indications and carrying at least one high-risk factor, including CLL-IPI high-risk/very high-risk, del(11q), del(17p)/TP53 mutation, unmutated IGHV, or complex karyotype.
‣ Measurable disease: presence of measurable lymphadenopathy by computed tomography (CT) scan.
‣ ECOG performance status of 0 to 2.
‣ Adequate major organ function meeting the following criteria:
⁃ Hematologic function: without transfusion or hematopoietic growth factor support for at least 7 days prior to enrollment (at least 14 days for pegylated G-CSF such as pegfilgrastim), and meeting the following criteria: absolute neutrophil count (ANC) \> 0.75 × 10⁹/L, platelet count (PLT) \> 30 × 10⁹/L, hemoglobin (Hb) \> 80 g/L.
⁃ Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 3.0 × upper limit of normal (ULN).
⁃ Creatinine clearance (CrCl) ≥ 60 mL/min (estimated by Cockcroft-Gault formula).
⁃ Total bilirubin (TBIL) ≤ 1.5 × ULN (unless due to Gilbert's syndrome or other non-hepatic causes).
⁃ Coagulation function: prothrombin time (PT)/international normalized ratio (INR) \< 1.5 × ULN, activated partial thromboplastin time (APTT) \< 1.5 × ULN (exceptions may be considered on a case-by-case basis if clearly unrelated to coagulopathy or bleeding disorders).
‣ Life expectancy ≥ 6 months. Female subjects of non-childbearing potential (e.g., postmenopausal for ≥ 1 year with amenorrhea, history of hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) are eligible. Female subjects of childbearing potential must have a negative serum pregnancy test at enrollment.
‣ Able to understand and voluntarily sign a written informed consent form.