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

NCT ID: NCT07003464

Last Updated: 2025-06-04

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-15
• Study Completion Date: 2028-06-01

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.

Conditions

Chronic Lymphocytic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ZGB arm

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.

Group Type: EXPERIMENTAL

Zanubrutinib

Intervention Type: DRUG

160 mg (2 tablets) BID. Each 4-week period constitutes one treatment cycle.

Obinutuzumab

Intervention Type: DRUG

1000 mg IV (Days 1, 8, 15 of Cycle 1; Day 1 thereafter).Each 4-week period constitutes one treatment cycle.

Bendamustine

Intervention Type: DRUG

70 mg/m² (Days 1-2 per cycle) for induction only (Cycles 1-4).Each 4-week period constitutes one treatment cycle.

Interventions

Zanubrutinib

160 mg (2 tablets) BID. Each 4-week period constitutes one treatment cycle.

Intervention Type: DRUG

Obinutuzumab

1000 mg IV (Days 1, 8, 15 of Cycle 1; Day 1 thereafter).Each 4-week period constitutes one treatment cycle.

Intervention Type: DRUG

Bendamustine

70 mg/m² (Days 1-2 per cycle) for induction only (Cycles 1-4).Each 4-week period constitutes one treatment cycle.

Intervention Type: DRUG

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Hospital of Jilin University

OTHER

Sponsor Role: lead

Responsible Party

Ou Bai, MD/PHD

Director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

The First Hospital of Jilin University

Changchun, Jilin, China

Countries

China

Central Contacts

Ou Bai, MD/PHD

Role: CONTACT

oubai16@163.com

13039046656

Facility Contacts

Ou Bai, MD/PHD

Role: primary

oubai16@163.com

13039046656

Other Identifiers

HEM-2024-ZGB-01

Identifier Type: -

Identifier Source: org_study_id