Phase II Trial of Zanubrutinib, Obinutuzumab, Bendamustine (ZGB) as First-Line Therapy for Chronic Lymphocytic Leukemia: A Single-Center Study

Официальное название

Efficacy and Safety of Zanubrutinib, Obinutuzumab, and Bendamustine (ZGB) Regimen for First-Line Treatment of Chronic Lymphocytic Leukemia: A Single-Arm, Prospective Study

Обзор

This is a single arm, open label, national multicenter clinical study included patients with chronic lymphocytic leukemia (CLL). The treatment combines three medications: Zanubrutinib , Obinutuzumab and Bendamustine . Together, these drugs aim to achieve deep remission (no detectable cancer cells) and allow a shorter treatment duration compared to lifelong therapies.

Вмешательства

• Препарат Zanubrutinib
  160 mg (2 tablets) BID. Each 4-week period constitutes one treatment cycle.
• Препарат Obinutuzumab
  1000 mg IV (Days 1, 8, 15 of Cycle 1; Day 1 thereafter).Each 4-week period constitutes one treatment cycle.
• Препарат Bendamustine
  70 mg/m² (Days 1-2 per cycle) for induction only (Cycles 1-4).Each 4-week period constitutes one treatment cycle.

Первичные конечные точки

• Undetectable Minimal Residual Disease (uMRD) Rate [Срок оценки: Assessed at the end of Cycle 6 (each cycle = 28 days).]

Вторичные конечные точки (5)

• Overall Response Rate (ORR) [Срок оценки: Assessed every 2 cycles during treatment and confirmed at Cycle 6 (each cycle = 28 days)]
• Complete Response Rate (CRR) [Срок оценки: Assessed every 2 cycles during treatment and confirmed at Cycle 6 (each cycle = 28 days)]
• Progression-Free Survival (PFS) [Срок оценки: Evaluated every 3 months post-treatment for up to 3 years.]
• Overall Survival (OS) [Срок оценки: Follow-up until study completion (3 years).]
• Incidence of Treatment-Emergent Adverse Events (TEAEs) [Срок оценки: From first dose to 30 days after last dose.]

Критерии участия

Критерии включения

• Demographics: Age ≥18 years, regardless of gender.
• Diagnosis: Confirmed diagnosis of untreated chronic lymphocytic leukemia (CLL) per iwCLL 2018 criteria.
• Treatment Naivety:

• No prior systemic therapy for CLL, including:
• CHOP/COP-based chemotherapy.
• Regimens containing fludarabine or bendamustine.
• Anti-CD20 monoclonal antibodies (e.g., rituximab) or BTK inhibitors (e.g., ibrutinib).
• Chlorambucil or cyclophosphamide (>3 weeks of use).
• Interferon therapy (>6 months of use).
• Treatment Indications:

• Must meet ≥1 of the following (iwCLL 2018 criteria):
• Hemoglobin <100 g/L (non-hemolytic).
• Platelets <100×10⁹/L with progressive decline.
• Lymphadenopathy (longest diameter >10 cm) or massive splenomegaly (>6 cm below costal margin).
• Constitutional symptoms: unexplained fever (>38°C ×2 weeks), night sweats, or >10% weight loss in 6 months.
• Rapid disease progression (lymphocyte doubling time <6 months, 50% lymph node growth in 2 months, or rapid cytopenia).
• Performance Status: ECOG performance status ≤2.
• Organ Function (within 7 days before enrollment):

Hematologic:

• ANC ≥1.0×10⁹/L (without growth factor support).
• Platelets ≥50×10⁹/L (without transfusion).
• Hepatic: AST/ALT ≤2.5×ULN; total bilirubin ≤1.5×ULN.
• Renal: Estimated CrCl ≥30 mL/min (Cockcroft-Gault formula).
• Consent: Signed informed consent.

Критерии исключения

• Malignancy: History of active malignancy (excluding CLL) within the past year, including CNS lymphoma.
• Disease Transformation: Richter transformation or prolymphocytic leukemia (PLL).
• Autoimmune Cytopenias: Active autoimmune hemolysis or thrombocytopenia requiring corticosteroids.
• Organ Dysfunction: ALT/AST >3×ULN; total bilirubin >2×ULN; creatinine >1.5×ULN.
• Comorbidities: Uncontrolled diabetes, cardiac/pulmonary disease, or conditions deemed by investigators to affect study safety.
• Infections: Active systemic infection requiring IV antibiotics.
• Bleeding Risks: History of life-threatening hemorrhage or need for high-dose anticoagulation.
• Recent Surgery: Major surgery within 30 days.
• Reproductive Status: Pregnancy, lactation, or unwillingness to use contraception.
• Drug Tolerance: Hypersensitivity to any study drug components.
• Viral Infections: Active HBV (HBsAg+ or HBV-DNA+) or HCV.
• Other: Investigator-determined ineligibility (e.g., poor compliance, psychiatric disorders).

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

• The First Hospital of Jilin University — Changchun

Идентификаторы

NCT: NCT07003464 · HEM-2024-ZGB-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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