Chronic Lymphocytic Leukemia
Conditions
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.
Interventions
DRUGZanubrutinib
160 mg (2 tablets) BID. Each 4-week period constitutes one treatment cycle.
DRUGObinutuzumab
1000 mg IV (Days 1, 8, 15 of Cycle 1; Day 1 thereafter).Each 4-week period constitutes one treatment cycle.
DRUGBendamustine
70 mg/m² (Days 1-2 per cycle) for induction only (Cycles 1-4).Each 4-week period constitutes one treatment cycle.
Sponsors
The First Hospital of Jilin University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
China
Contacts
Primary ContactOu Bai, MD/PHD
Outcome results
None listed