Clinical trial NCT07003464: Phase II Trial of Zanubrutinib, Obinutuzumab, Bendamustine (ZGB) as First-Line Therapy for Chronic Lymphocytic Leukemia: A Single-Center Study
Official title: Efficacy and Safety of Zanubrutinib, Obinutuzumab, and Bendamustine (ZGB) Regimen for First-Line Treatment of Chronic Lymphocytic Leukemia: A Single-Arm, Prospective Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Chronic Lymphocytic Leukemia
Lead sponsor: The First Hospital of Jilin University
Sponsor class: OTHER
First posted: 2025-06-04
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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.
Primary purpose: TREATMENT

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.


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).

Primary outcomes:
measure: Undetectable Minimal Residual Disease (uMRD) Rate
timeFrame: Assessed at the end of Cycle 6 (each cycle = 28 days).
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Assessed every 2 cycles during treatment and confirmed at Cycle 6 (each cycle = 28 days)
measure: Complete Response Rate (CRR)
timeFrame: Assessed every 2 cycles during treatment and confirmed at Cycle 6 (each cycle = 28 days)
measure: Progression-Free Survival (PFS)
timeFrame: Evaluated every 3 months post-treatment for up to 3 years.
measure: Overall Survival (OS)
timeFrame: Follow-up until study completion (3 years).
measure: Incidence of Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From first dose to 30 days after last dose.
Other outcomes:
Locations:
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
Study officials:
References: