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

August 15, 2025 updated by: The First Affiliated Hospital with Nanjing Medical University

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

15

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Jiangsu
      • Nanjing, Jiangsu, China, 210000
        • Recruiting
        • Jiangsu Province Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ZBG
Drug: zanubrutinib, bendamustine, and obinutuzumab

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
2-year PFS
Time Frame: 2 year
2-year progression-free survival (PFS)
2 year

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The First Affiliated Hospital with Nanjing Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 15, 2025

Primary Completion (Estimated)

July 15, 2028

Study Completion (Estimated)

December 30, 2028

Study Registration Dates

First Submitted

July 21, 2025

First Submitted That Met QC Criteria

August 15, 2025

First Posted (Actual)

August 17, 2025

Study Record Updates

Last Update Posted (Actual)

August 17, 2025

Last Update Submitted That Met QC Criteria

August 15, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FL-ZBG-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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