Prospective Exploratory Study of Fixed-Duration Zanubrutinib, Bendamustine, and Obinutuzumab (ZBG) in Treatment-Naïve Advanced Stage Follicular Lymphoma
This study investigates a fixed-duration regimen of zanubrutinib, bendamustine, and obinutuzumab (ZBG) in the treatment of treatment-naïve patients with advanced-stage follicular lymphoma. Patients will receive combination therapy with zanubrutinib, bendamustine, and obinutuzumab over 6 cycles, with each cycle lasting 28 days. The specific dosing schedule is as follows: Bendamustine 70 mg/m²: administered intravenously on Days 2-3 of Cycle 1, and on Days 1-2 of Cycles 2-6. Obinutuzumab 1000 mg: administered intravenously on Days 1, 8, and 15 of Cycle 1, and on Day 1 of Cycles 2-6 (every 28-day cycle). Zanubrutinib 160 mg orally twice daily (bid), continuously throughout Cycles 1-6. Treatment is discontinued after 6 cycles, with no subsequent maintenance therapy. Primary endpoint is 2-year PFS. Secondary endpoints include: CR rate after 6 cycles, ORR after 3 and 6 cycles MRD-negative rate after 3 and 6 cycles, OS, safety and tolerability.
• Voluntary participation with signed informed consent;
• Age ≥18 years and ≤75 years, regardless of gender;
• Life expectancy ≥3 months;
• ECOG performance status 0-2; patients with ECOG 3 may be enrolled only if their decline in performance status is disease-related and the investigator judges they may benefit from treatment;
• Histologically confirmed diagnosis of grade I, II, or IIIa follicular lymphoma (FL), treatment-naïve, stage III-IV disease, and meeting treatment criteria (GELF criteria);
• Measurable and/or evaluable lymphoma lesions;
• Adequate bone marrow reserve: absolute neutrophil count (ANC) \>1.0×10⁹/L or platelets \>75×10⁹/L, unless cytopenia is deemed related to bone marrow infiltration by lymphoma and the investigator believes it may recover;
• Liver function: AST (SGOT), ALT (SGPT) ≤2.5×ULN (without liver involvement) or ≤5×ULN (with liver involvement); total bilirubin (TBIL) ≤ULN; serum creatinine (CRE) ≤1.5×ULN;
• Creatinine clearance ≥30 mL/min (calculated by Cockcroft-Gault formula);
⁃ Ability to comply with study visit schedules and other protocol requirements;
⁃ All patients of childbearing potential must agree to use effective contraception during the study and for 24 months after treatment cessation; women of childbearing potential must have a negative urine pregnancy test before treatment initiation.