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

Not Applicable

Recruiting

• Conditions: Follicular Lymphoma; Treatment Naive
• Interventions: Drug: zanubrutinib, bendamustine, and obinutuzumab

• Registration Number: NCT07126678
• Lead Sponsor: The First Affiliated Hospital with Nanjing Medical University

Brief 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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-07
• Study Start: 2025-07-15
• Study First Submitted: 2025-07-21
• Study First Submitted QC: 2025-08-15
• Last Update Submitted: 2025-08-15
• Study First Posted: 2025-08-17
• Last Update Posted: 2025-08-17
• Primary Completion: 2028-07-15
• Study Completion: 2028-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 15

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ZBG	zanubrutinib, bendamustine, and obinutuzumab	-

Primary Outcome Measures

Name	Time	Method
2-year PFS	2 year	2-year progression-free survival (PFS)

Secondary Outcome Measures

Name	Time	Method
CR Rate	At the end of Cycle 6 (each cycle is 28 days)	complete remission rate
ORR	At the end of Cycle 3 and 6 (each cycle is 28 days)	objective remission rate
MRD	At the end of Cycle 6 (each cycle is 28 days)	minimal residue rate
OS	From date of randomization until the date of death from any cause, assessed up to 100 months	Overall survival
Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE	2 year	* Adverse events and serious adverse events; * Treatment-related adverse events leading to dose adjustments, dose interruptions, delays, and/or study drug discontinuation

Trial Locations

Locations (1)

Jiangsu Province Hospital; 🇨🇳 Nanjing, Jiangsu, China