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

NCT07003464 | Not Yet Recruiting Phase 2

• 1 other identifier: HEM-2024-ZGB-01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Undetectable Minimal Residual Disease (uMRD) Rate

  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.

  Assessed at the end of Cycle 6 (each cycle = 28 days).

Secondary Outcomes (5)

• Overall Response Rate (ORR)

  Assessed every 2 cycles during treatment and confirmed at Cycle 6 (each cycle = 28 days)

• Complete Response Rate (CRR)

  Assessed every 2 cycles during treatment and confirmed at Cycle 6 (each cycle = 28 days)

• Progression-Free Survival (PFS)

  Evaluated every 3 months post-treatment for up to 3 years.

• Overall Survival (OS)

  Follow-up until study completion (3 years).

• Incidence of Treatment-Emergent Adverse Events (TEAEs)

  From first dose to 30 days after last dose.

Study Arms (1)

ZGB arm

EXPERIMENTAL

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.

Drug: Zanubrutinib; Drug: Obinutuzumab; Drug: Bendamustine

Interventions

Zanubrutinib DRUG

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

ZGB arm

Obinutuzumab DRUG

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

ZGB arm

Bendamustine DRUG

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

ZGB arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• The First Hospital of Jilin University: lead

Study Sites (1)

The First Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

zanubrutinib; obinutuzumab; Bendamustine Hydrochloride

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Ou Bai, MD/PHD

CONTACT

13039046656; oubai16@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Model Details: This trial follows a 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.

Study Record Dates

• First Submitted: May 26, 2025
• First Posted: June 4, 2025
• Study Start: June 15, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: June 4, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)