Fixed-Duration Zanubrutinib, Bendamustine, and Obinutuzumab (ZBG) in Treatment-Naïve Advanced Stage Follicular Lymphoma

Launched by THE FIRST AFFILIATED HOSPITAL WITH NANJING MEDICAL UNIVERSITY · Aug 15, 2025

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment approach for people who have advanced follicular lymphoma, a type of slow-growing blood cancer, and who have not yet received any treatment for it. The treatment combines three medicines—zanubrutinib (taken as pills), bendamustine, and obinutuzumab (both given through an IV)—over six cycles, each lasting about 28 days. After these six cycles, the treatment stops, and there is no ongoing maintenance therapy. The main goal is to see how well this fixed treatment schedule works to keep the cancer from getting worse over two years, along with how well patients respond to treatment and how safe the medicines are.

People who might be eligible for this study are adults between 18 and 75 years old with confirmed advanced-stage follicular lymphoma who have not had previous treatment. They need to be generally healthy enough to receive the treatment and able to follow the study schedule. Before joining, patients will have tests to make sure their organs are working well enough and that they don’t have any serious infections or other health problems that could make the treatment unsafe. Participants will receive the combination treatment over about six months and will have regular check-ups to monitor how they are doing. This study is currently recruiting, so if you or a loved one fits these criteria and is interested, you might want to talk to your doctor about the possibility of joining.

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Eligibility criteria

• Inclusion Criteria:
• • 1. Voluntary participation with signed informed consent;
• • 2. Age ≥18 years and ≤75 years, regardless of gender;
• • 3. Life expectancy ≥3 months;
• • 4. 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;
• • 5. Histologically confirmed diagnosis of grade I, II, or IIIa follicular lymphoma (FL), treatment-naïve, stage III-IV disease, and meeting treatment criteria (GELF criteria);
• • 6. Measurable and/or evaluable lymphoma lesions;
• • 7. 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;
• • 8. 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;
• • 9. Creatinine clearance ≥30 mL/min (calculated by Cockcroft-Gault formula);
• • 10. Ability to comply with study visit schedules and other protocol requirements;
• • 11. 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 Criteria:
• • 1. Grade IIIb FL or transformed FL;
• • 2. Received lymphoma-directed therapy within 2 weeks prior to enrollment;
• 3. 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;
• • 4. Known active hepatitis C virus (HCV) infection; other acquired/congenital immunodeficiency disorders, including HIV infection;
• • 5. Central nervous system (CNS) involvement by lymphoma;
• 6. 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;
• • 7. Hypersensitivity to any study drug;
• • 8. Pregnant or breastfeeding women;
• • 9. History of stroke or intracranial hemorrhage within 6 months before enrollment;
• • 10. Requiring anticoagulation with warfarin or equivalent vitamin K antagonists;
• • 11. Requiring chronic use of strong CYP3A inhibitors;
• • 12. Administration of live attenuated vaccines within 4 weeks before study entry.