Fixed-duration zanubrutinib plus bendamustine and obinutuzumab for newly diagnosed advanced follicular lymphoma

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

This tests a six-cycle combination of zanubrutinib, bendamustine, and obinutuzumab for adults with newly diagnosed advanced-stage follicular lymphoma.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: The First Affiliated Hospital with Nanjing Medical University (other)
• Drugs / interventions: obinutuzumab, zanubrutinib
• Locations: 1 site (Nanjing, Jiangsu)
• Trial ID: NCT07126678 on ClinicalTrials.gov

What this trial studies

This single-arm interventional trial gives treatment-naïve adults with stage III–IV follicular lymphoma six 28-day cycles of zanubrutinib (160 mg orally twice daily), bendamustine (70 mg/m² IV on specified days), and obinutuzumab (1000 mg IV on a defined schedule). Treatment stops after six cycles with no maintenance therapy. The primary goal is two-year progression-free survival; secondary outcomes include complete response rate after six cycles, overall response rates after three and six cycles, MRD negativity, overall survival, and safety. The study is conducted at Jiangsu Province Hospital (Nanjing) under the lead of The First Affiliated Hospital with Nanjing Medical University.

Who should consider this trial

Good fit: Adults 18–75 years old with untreated, histologically confirmed grade I–IIIa follicular lymphoma at stage III–IV who meet GELF treatment criteria and have adequate organ function are ideal candidates.

Not a fit: Patients with prior systemic therapy for lymphoma, grade IIIb disease, major uncontrolled medical conditions, or inadequate blood, liver, or kidney function are unlikely to qualify or benefit from this regimen.

Why it matters

Potential benefit: If successful, this fixed-duration regimen could provide durable remissions without the need for ongoing maintenance therapy.

How similar studies have performed: BTK inhibitors combined with anti-CD20 antibodies have shown activity in B-cell lymphomas, but a fixed-duration frontline zanubrutinib plus bendamustine and obinutuzumab regimen is relatively novel and not yet proven in large randomized trials.

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.

Where this trial is running

Nanjing, Jiangsu

• Jiangsu Province Hospital — Nanjing, Jiangsu, China (RECRUITING)

Study contacts

• Study coordinator: Yi Xia

Conditions: Follicular Lymphoma, Treatment Naive, Follicular lymphoma, fixed-duration, zanubrutinib, ZBG