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

Phase 2

Not yet recruiting

• Conditions: Chronic Lymphocytic Leukemia
• Interventions: Drug: Zanubrutinib; Drug: Obinutuzumab; Drug: Bendamustine

• Registration Number: NCT07003464
• Lead Sponsor: The First Hospital of Jilin University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-03
• Study First Submitted: 2025-05-26
• Study First Submitted QC: 2025-06-03
• Last Update Submitted: 2025-06-03
• Study First Posted: 2025-06-04
• Last Update Posted: 2025-06-04
• Study Start: 2025-06-15
• Primary Completion: 2027-06-01
• Study Completion: 2028-06-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 30

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ZGB arm	Zanubrutinib	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.
ZGB arm	Obinutuzumab	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.
ZGB arm	Bendamustine	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.

Primary Outcome Measures

Name	Time	Method
Undetectable Minimal Residual Disease (uMRD) Rate	Assessed at the end of Cycle 6 (each cycle = 28 days).	Proportion of participants achieving uMRD (defined as \<1 CLL cell per 10,000 leukocytes \[\<0.01%\] via 8-color flow cytometry) in peripheral blood after 6 cycles of therapy.

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR)	Assessed every 2 cycles during treatment and confirmed at Cycle 6 (each cycle = 28 days)	Proportion of participants achieving complete response (CR), partial response (PR), or partial response with lymphocytosis (PR-L) per iwCLL 2018 criteria.
Complete Response Rate (CRR)	Assessed every 2 cycles during treatment and confirmed at Cycle 6 (each cycle = 28 days)	Proportion of participants achieving CR (normalization of blood counts, lymph nodes/spleen size, and bone marrow with \<30% lymphocytes).
Progression-Free Survival (PFS)	Evaluated every 3 months post-treatment for up to 3 years.	Time from enrollment to disease progression (per iwCLL 2018) or death from any cause.
Overall Survival (OS)	Follow-up until study completion (3 years).	Time from enrollment to death from any cause.
Incidence of Treatment-Emergent Adverse Events (TEAEs)	From first dose to 30 days after last dose.	Frequency and severity of adverse events graded per NCI CTCAE v5.0.

Trial Locations

Locations (1)

The First Hospital of Jilin University; 🇨🇳 Changchun, Jilin, China