Zanubrutinib Induction Followed by Delayed Fixed-Duration Combination With Sonrotoclax for CLL/SLL：Stop Trial 2.0

Lab values

• 1\. Previously received any systemic anti-tumor therapy for CLL/SLL. 2. Pathologically confirmed transformation to Richter's syndrome via biopsy. 3. Severe non-lymphoma-related hepatic or renal impairment defined as: ALT/AST \>3×ULN or TBIL \>2×ULN; creatinine clearance \<30 mL/min or serum creatinine \>2×ULN.
  • 4\. Significant pre-existing renal, neurological, psychiatric, pulmonary, endocrine, metabolic, immune, cardiovascular or hepatic disease judged by the investigator to compromise trial participation.
  • 5\. Other uncontrolled clinically significant medical conditions including but not limited to:
  • Uncontrolled systemic infection (viral, bacterial, fungal); positive hepatitis B surface antigen with HBV-DNA \>1000 IU/mL; positive anti-HCV antibody or detectable HCV-RNA; positive anti-HIV antibody.
  • Active uncontrolled autoimmune diseases other than autoimmune cytopenias. 6. Clinical signs of central nervous system (CNS) dysfunction or documented CNS infiltration by disease.
  • 7\. Received major surgery (excluding lymph node biopsy) within 14 days prior to enrollment or scheduled to undergo major surgery during trial treatment.
  • 8\. Inability to swallow capsules, malabsorption syndrome, or severe gastrointestinal disorders including prior gastrectomy, small bowel resection, symptomatic inflammatory bowel disease, ulcerative colitis, partial or complete intestinal obstruction.
  • 9\. Concurrent use of strong CYP3A inhibitors or inducers during study drug initiation and dose titration period.
  • 10\. Pregnant or breastfeeding females; females of childbearing potential without reliable contraceptive measures.
  • 11\. Clinically significant cardiovascular disease (NYHA cardiac functional class III/IV); history of myocardial infarction, malignant arrhythmia (including QTc ≥480 ms), inadequately controlled hypertension (systolic BP ≥150 mmHg, diastolic BP ≥100 mmHg) or unstable angina within 6 months before enrollment.
  • 12\. Coagulopathy-related exclusion: long-term treatment with multiple high-dose anticoagulants with no possibility of short-term discontinuation; persistent uncontrolled active bleeding; or prior life-threatening irreversible bleeding events.
  • 13\. History of severe hypersensitivity to any active ingredient or excipient of the investigational product.
  • 14\. Systemic disorders that may impair patient compliance with trial requirements.

• Aged ≥18 years, no restriction on gender.
• Newly diagnosed chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) consistent with the Chinese Guidelines for the Diagnosis and Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (2025 Edition).
• Meet at least one of the following indications for CLL treatment:
  • Evidence of progressive bone marrow failure manifested by progressive reduction in hemoglobin and/or platelet counts.
  • Massive splenomegaly (spleen palpable \>6 cm below the left costal margin) or symptomatic splenomegaly.
  • Bulky lymphadenopathy (maximum diameter \>10 cm) or symptomatic lymphadenopathy.
  • Progressive lymphocytosis: ≥50% increase in lymphocyte count within 2 months, or lymphocyte doubling time (LDT) \<6 months. LDT alone shall not serve as an indication for treatment if the baseline lymphocyte count is \<30×10⁹/L.
  • Symptomatic organ dysfunction caused by CLL/SLL (involving skin, kidney, lung, spine and other organs).
  • Autoimmune hemolytic anemia (AIHA) and/or immune thrombocytopenia (ITP) with inadequate response to corticosteroid therapy.
  • At least one of the following disease-related B symptoms:
  • Unintentional weight loss ≥10% within the preceding 6 months without identifiable cause; ② Severe fatigue (ECOG performance status ≥2, inability to perform routine daily activities);
  • ③ Unexplained fever \>38.0 °C lasting ≥2 weeks without confirmed infection;
  • ④ Unexplained night sweats persisting for more than 1 month without confirmed infection.
• ECOG performance status ≤2.
• Major organ function meets the following criteria within 7 days prior to treatment initiation:
  • ￮ Hematology: platelet count ≥30×10⁹/L;
  • ￮ Biochemistry: total bilirubin (TBIL) ≤1.5×upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN; creatinine clearance ≥30 mL/min;
  • ￮ Cardiac Doppler echocardiography: left ventricular ejection fraction (LVEF) ≥lower limit of normal (50%).
• Male and female participants agree to use effective contraception throughout the study period and for a minimum of 4 weeks after treatment completion.
• Estimated life expectancy ≥6 months.
• The patient voluntarily participates in the trial and signs the written informed consent form.