Combination of Zanubrutinib, Rituximab and Venetoclax in Patients With Previously Untreated Follicular Lymphoma

• A diagnosis of follicular lymphoma (grades 1, 2, or 3a), untreated.
• Stage II, III, or IV disease.
• Able and willing to provide written informed consent and to comply with the study protocol.
• at least one measurable disease.

• Must be in need of therapy as evidenced by at least one of the following criteria:

  • Presence of at least one B symptom: Fever (> 38 Celsius [C]) not due to infectious etiology, or Night sweats, or Weight loss > 10% in the past 6 months;
  • Fatigue due to lymphoma;
  • Splenomegaly (> 13 cm);
  • Compression syndrome (ureteral, orbital, gastrointestinal);
  • Any of the following cytopenias, due to lymphoma: Hemoglobin ≤ 10 g/dL, or Platelets ≤ 100 x 10\^9/L, or Absolute neutrophil count (ANC) \< 1.5 x 10\^9/L;
  • Pleural or peritoneal effusion;
  • Lactate dehydrogenase (LDH) > upper limit of normal (ULN) or beta (B)2 microglobulin > ULN;
  • Other lymphoma-mediated symptoms as determined by the treating physician.
• ECOG ≤ 2
• ANC > 1.0 x 10\^9/L (for patients without bone marrow involvement by lymphoma)
• Platelet count > 50 x 10\^9/L (for patients without bone marrow involvement by lymphoma)
• Prothrombin time (PT)/international normal ratio (INR) \< 1.5 x (upper limit of normal) ULN and partial thromboplastin time (PTT) (activated partial thromboplastin time [aPTT]) \< 1.5 x ULN (unless abnormalities are unrelated to coagulopathy or bleeding disorder). When treated with warfarin or other vitamin K antagonists, then INR ≤ 3.0)
• Serum aspartate transaminase (AST) and alanine transaminase (ALT) \< 3 x ULN
• Creatinine clearance > 30 ml/min calculated by modified Cockcroft-Gault formula
• Bilirubin \< 1.5 x ULN unless bilirubin is due to Gilbert's syndrome, documented liver involvement with lymphoma, or of non-hepatic origin, in which case bilirubin should not exceed 3 g/dL
• Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [B-hCG]) pregnancy test at screening. Women who are pregnant or breastfeeding are ineligible for this study

Exclusion Criteria:

• Known active central nervous system lymphoma or leptomeningeal disease
• Follicular lymphoma with evidence of diffuse large B-cell transformation
• Grade 3b follicular lymphoma
• Any prior history of other malignancy besides follicular lymphoma
• History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
• Patients who have undergone major surgery within 14 days
• The researchers believe that it is not advisable for the participant to take part in this trial.