Safety and Efficacy of Zanubrutinib in Combination With Rituximab and Venetoclax in Previously Untreated Follicular Lymphoma: An Open Label, Phase 2 Study
This is a single center, open label, single arm phase II clinical trial. The objective of this study is to assess the feasibility and efficacy of zanubrutinib combined with venetoclax and Rituximab in patients with previously untreated follicular lymphoma (FL) .
• 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