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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат 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

Первичные конечные точки

• 2-year PFS [Срок оценки: 2 year]

Вторичные конечные точки (5)

• CR Rate [Срок оценки: At the end of Cycle 6 (each cycle is 28 days)]
• ORR [Срок оценки: At the end of Cycle 3 and 6 (each cycle is 28 days)]
• MRD [Срок оценки: At the end of Cycle 6 (each cycle is 28 days)]
• OS [Срок оценки: 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 [Срок оценки: 2 year]

Критерии участия

Критерии включения

• Voluntary participation with signed informed consent;
• Age ≥18 years and ≤75 years, regardless of gender;
• Life expectancy ≥3 months;
• 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;
• Histologically confirmed diagnosis of grade I, II, or IIIa follicular lymphoma (FL), treatment-naïve, stage III-IV disease, and meeting treatment criteria (GELF criteria);
• Measurable and/or evaluable lymphoma lesions;
• 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;
• 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;
• Creatinine clearance ≥30 mL/min (calculated by Cockcroft-Gault formula);
• Ability to comply with study visit schedules and other protocol requirements;
• 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.

Критерии исключения

• Grade IIIb FL or transformed FL;
• Received lymphoma-directed therapy within 2 weeks prior to enrollment;
• 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;
• Known active hepatitis C virus (HCV) infection; other acquired/congenital immunodeficiency disorders, including HIV infection;
• Central nervous system (CNS) involvement by lymphoma;
• 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;
• Hypersensitivity to any study drug;
• Pregnant or breastfeeding women;
• History of stroke or intracranial hemorrhage within 6 months before enrollment;
• Requiring anticoagulation with warfarin or equivalent vitamin K antagonists;
• Requiring chronic use of strong CYP3A inhibitors;
• Administration of live attenuated vaccines within 4 weeks before study entry.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Jiangsu Province Hospital — Нанкин

Публикации

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• Zinzani PL, Mayer J, Flowers CR, Bijou F, De Oliveira AC, Song Y, Zhang Q, Merli M, Bouabdallah K, Ganly P, Zhang H, Johnson R, Martin Garcia-Sancho A, Provencio Pulla M, Trneny M, Yuen S, Tilly H, Kingsley E, Tumyan G, Assouline SE, Auer R, Ivanova E, Kim P, Huang S, Delarue R, Trotman J. ROSEWOOD: A Phase II Randomized Study of Zanubrutinib Plus Obinutuzumab Versus Obinutuzumab Monotherapy in Pa PMID 37506346
• Zinzani PL, Munoz J, Trotman J. Current and future therapies for follicular lymphoma. Exp Hematol Oncol. 2024 Aug 22;13(1):87. doi: 10.1186/s40164-024-00551-1. PMID 39175100
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• Pott C, Jurinovic V, Trotman J, Kehden B, Unterhalt M, Herold M, Jagt RV, Janssens A, Kneba M, Mayer J, Young M, Schmidt C, Knapp A, Nielsen T, Brown H, Spielewoy N, Harbron C, Bottos A, Mundt K, Marcus R, Hiddemann W, Hoster E. Minimal Residual Disease Status Predicts Outcome in Patients With Previously Untreated Follicular Lymphoma: A Prospective Analysis of the Phase III GALLIUM Study. J Clin O PMID 38096461
• Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trneny M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the First-Line Treatment of Follicular Lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. doi: 10.1056/NEJMoa1614598. PMID 28976863
• Casulo C, Byrtek M, Dawson KL, Zhou X, Farber CM, Flowers CR, Hainsworth JD, Maurer MJ, Cerhan JR, Link BK, Zelenetz AD, Friedberg JW. Early Relapse of Follicular Lymphoma After Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Defines Patients at High Risk for Death: An Analysis From the National LymphoCare Study. J Clin Oncol. 2015 Aug 10;33(23):2516-22. doi: 10.1200/JCO. PMID 26124482

Идентификаторы

NCT: NCT07126678 · FL-ZBG-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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