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

Inclusion Criteria:

• 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 studyprotocol

• 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

• Night sweats

• 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

• Platelets ≤ 100 x 10^9/L

• 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

Exclusion Criteria:

• ECOG≤ 2

• Absolute neutrophil count (ANC) > 1.0 x 10^9/L

• Platelet count > 50 x 10^9/L

• Prothrombin time (PT)/international normal ratio (INR) < 1.5 x (upper limit ofnormal) ULN and partial thromboplastin time (PTT) (activated partial thromboplastintime [aPTT]) < 1.5 x ULN (unless abnormalities are unrelated to coagulopathy orbleeding disorder). When treated with warfarin or other vitamin K antagonists, thenINR ≤ 3.0)

• Serum aspartate transaminase (AST) and alanine transaminase (ALT) < 3 x upper limitof normal (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, documentedliver involvement with lymphoma, or of non-hepatic origin, in which case bilirubinshould not exceed 3 g/dL

• Women of childbearing potential must have a negative serum (beta-human chorionicgonadotropin [B-hCG]) pregnancy test at screening. Women who are pregnant orbreastfeeding 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 inthis trial.