Follicular Lymphoma, Treatment Naive
Conditions
Keywords
Follicular lymphoma, fixed-duration, zanubrutinib, ZBG, Treatment Naive
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.
Interventions
DRUGzanubrutinib, 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.
Sponsors
The First Affiliated Hospital with Nanjing Medical University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 2-year PFS | 2 year | 2-year progression-free survival (PFS) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
China
Contacts
Primary ContactYi Xia
Backup ContactJianyong Li Li
Outcome results
None listed