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

Jilin University

Status and phase: Begins enrollment this month; Phase 2

Conditions: Chronic Lymphocytic Leukemia

Treatments: Drug: Bendamustine; Drug: Zanubrutinib; Drug: Obinutuzumab

Study type: Interventional

Funder types: Other

Identifiers

NCT07003464

HEM-2024-ZGB-01

Details and patient eligibility

About

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.

Enrollment: 30 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Demographics: Age ≥18 years, regardless of gender.

2. Diagnosis: Confirmed diagnosis of untreated chronic lymphocytic leukemia (CLL) per iwCLL 2018 criteria.

3. 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).

4. 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).

5. Performance Status: ECOG performance status ≤2.

6. 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).

7. Consent: Signed informed consent.

Exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

ZGB arm

Experimental group

Description:

Single-arm, two-stage, MRD-adapted design to assess both safety and preliminary efficacy of the ZGB regimen. Structure: Sequential Two-Stage Intervention： Induction Phase (Cycles 1-4): All participants receive Zanubrutinib + Obinutuzumab + Bendamustine (ZGB). Consolidation Phase (Cycles 5-6): Only participants achieving peripheral blood uMRD (\<0.01% by flow cytometry) after Cycle 4 receive Zanubrutinib + Obinutuzumab (ZG); others discontinue treatment.

Treatment:

Drug: Obinutuzumab

Drug: Zanubrutinib

Drug: Bendamustine