Fixed-Duration Zanubrutinib, Bendamustine, and Obinutuzumab (ZBG) in Treatment-Naïve Advanced Stage Follicular Lymphoma
Prospective Exploratory Study of Fixed-Duration Zanubrutinib, Bendamustine, and Obinutuzumab (ZBG) in Treatment-Naïve Advanced Stage Follicular Lymphoma
The First Affiliated Hospital with Nanjing Medical University
15 participants
Jul 15, 2025
INTERVENTIONAL
Conditions
Summary
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.
Eligibility
Inclusion Criteria11
- 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.
Exclusion Criteria25
- Grade IIIb FL or transformed FL;
- Received lymphoma-directed therapy within 2 weeks prior to enrollment;
- Any severe medical condition, including but not limited to:
- Poorly controlled hypertension (defined as failure to achieve control despite lifestyle modifications and treatment with at least 3 maximally tolerated antihypertensive drugs \[including diuretics\] for ≥4 weeks, or requiring ≥4 antihypertensive drugs for adequate control);
- Uncontrolled congestive heart failure (NYHA class 3 \[moderate\] or 4 \[severe\]) within 6 months prior to screening;
- Left ventricular ejection fraction (LVEF) \<50%;
- Symptomatic coronary artery disease (e.g., chest pain, palpitations, fatigue) or requiring medication;
- Severe bradycardia (heart rate \<40 bpm), hypotension, dizziness, or syncope; patients with arrhythmia history require cardiac evaluation;
- Active bacterial, viral, fungal, or other infections (except for nail fungal infections) or major infections within 2 weeks before the first dose of study drug;
- Moderate to severe liver disease (Child-Pugh B or C);
- Active bleeding within 2 months before screening or clinically significant bleeding tendency per investigator judgment;
- Pulmonary conditions impairing function (e.g., pulmonary fibrosis, drug-induced pneumonitis) deemed intolerable by the investigator;
- Any psychiatric or cognitive impairment that may compromise understanding of informed consent, protocol compliance, or study adherence;
- Known active hepatitis C virus (HCV) infection; other acquired/congenital immunodeficiency disorders, including HIV infection;
- Central nervous system (CNS) involvement by lymphoma;
- Diagnosis or treatment for malignancies other than lymphoma, except:
- Malignancies treated with curative intent and no evidence of disease for ≥5 years before enrollment;
- Adequately treated basal cell carcinoma (excluding melanoma) with no evidence of disease;
- Adequately treated cervical carcinoma in situ with no evidence of disease;
- Hypersensitivity to any study drug;
- Pregnant or breastfeeding women;
- History of stroke or intracranial hemorrhage within 6 months before enrollment;
- Requiring anticoagulation with warfarin or equivalent vitamin K antagonists;
- Requiring chronic use of strong CYP3A inhibitors;
- Administration of live attenuated vaccines within 4 weeks before study entry.
Interventions
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.
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT07126678