Clinical trial NCT06959732: Zanubrutinib Combined With G-CVP in Previously Untreated FL
Official title: Efficacy and Safety of Zanubrutinib Combined With G-CVP Regimen in Previously Untreated Follicular Lymphoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Follicular Lymphoma ( FL)
Keywords: Follicular Lymphoma ( FL)
Zanubrutinib
Obinutuzumab
CVP
Lead sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Sponsor class: OTHER
First posted: 2025-05-07
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to learn the efficacy and safety of zanubrutinib in combination with G-CVP in previously untreated follicular lymphoma patients The main questions it aims to answer are: (1) Efficacy and safety of patients receiving zanubrutinib, obinutuzumab combined with cyclophosphamide, vincristine, and prednisone (CVP) regimen. (2) The difference in efficacy of patients with different minimal residual disease (MRD) status after treatment.

Participants will receive zanubrutinib combined with G-CVP, maintenance therapy will be determined by the MRD status after treatment.

Detailed description: Follicular lymphoma (FL), accounting for nearly 20% of non - Hodgkin lymphomas, is an indolent B - cell neoplasm originating from follicular center B cells. Over 90% of patients are at stage Ⅲ/Ⅳ at onset. For stage Ⅲ/Ⅳ patients requiring treatment, CD20 monoclonal antibody - chemotherapy combinations are the most commonly used treatment both domestically and internationally. Though FL has a high response rate to traditional immunochemotherapy, it remains incurable by such means. Also, cytotoxic therapy's side effects are a key concern. There's an urgent need in clinical practice to enhance therapeutic efficacy while reducing side effects.

Obinutuzumab, a type II anti - CD20 monoclonal antibody, stands out from type I by boosting antitumor activity through enhanced direct cytotoxicity (DCD) and antibody - dependent cellular cytotoxicity (ADCC), and cutting complement - dependent cytotoxicity (CDC) - related resistance. Studies comparing obinutuzumab - chemotherapy with rituximab - chemotherapy in untreated FL have confirmed that the former brings sustained progression - free survival (PFS) benefits. Compared to CHOP or bendamustine combinations, it has a lower incidence of grade 3 - 5 adverse events when used with CVP, showing better tolerability. Zanubrutinib, a novel, highly - selective small - molecule BTK inhibitor developed in China, offers superior efficacy and safety due to its high kinase selectivity. Its combination with obinutuzumab has achieved remarkable results in relapsed/refractory FL patients.

In this study, we will treat untreated FL patients with zanubrutinib, obinutuzumab, and CVP chemotherapy. We expect this multi - mechanism drug combination to improve efficacy. Also, by replacing CHOP's anthracycline component, the regimen may provide better safety, thus offering a more effective and safer individualized treatment for untreated FL patients.

Untreated FL patients in the study will receive zanubrutinib, obinutuzumab, and CVP chemotherapy. Then, based on their MRD status, they'll undergo maintenance with either obinutuzumab alone or the combination. The primary endpoint is the complete remission (CR) rate; secondary endpoints include overall response rate (ORR), PFS, overall survival (OS), and adverse event (AE) rates.

Eligibility criteria: Inclusion Criteria:

Patients must meet all of the following criteria to be eligible:

1. Histologically confirmed CD20-positive FL (grades 1, 2, or 3a), diagnosed according to the WHO 2022 criteria; 2, Clear indication for treatment: symptoms affecting normal work and life; end-organ dysfunction; cytopenia due to bone marrow involvement by lymphoma; bulky disease (per GELF criteria); persistent or rapidly progressive disease; 3. No prior systemic therapy for lymphoma; 4. Age 18-80 years; 5. Eastern cooperative oncology group (ECOG) performance status (PS) \< 2; 6. Expected survival \> 2 years; 7. At least one measurable lesion with a longest diameter ≥ 1.5 cm or extranodal lesion ≥ 1 cm; 8. Willingness to participate in the study and comply with treatment and follow-up.

Exclusion Criteria:

Patients will be excluded if they meet any of the following criteria:

1. Pregnant or breastfeeding women;
2. Abnormal liver or kidney function, defined as: serum direct/indirect bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), or serum creatinine \> 2 × upper limit of normal (ULN); creatinine clearance \< 60 mL/min (unless due to lymphoma involvement);
3. History of deep vein thrombosis (DVT) or pulmonary embolism (PE) within the past 12 months;
4. Absolute neutrophil count (ANC) \< 1.5 × 10⁹/L, platelets \< 75 × 10⁹/L, or hemoglobin \< 70 g/L (unless due to bone marrow involvement by lymphoma);
5. Long-term use of strong or moderate CYP3A inducers;
6. Known hypersensitivity to any component of the study drug;
7. Other active malignancies, except: cured non-melanoma skin cancer, cervical carcinoma in situ, localized prostate cancer, superficial bladder cancer, ductal carcinoma in situ, or other malignancies with disease-free survival \> 5 years;
8. Severe concurrent infections;
9. Drug abuse, medical, psychological, or social conditions that may interfere with study participation or result evaluation;
10. Investigator-deemed ineligibility for the study.

Primary outcomes:
measure: CRR
timeFrame: From date of enrollment until the date of first documented CR assessed up to 2.5 years.
Secondary outcomes:
measure: ORR
timeFrame: From date of enrollment until the date of first documented response assessed up to 2.5 years.
measure: PFS
timeFrame: From date of enrollment until the date of first documented progression assessed up to 5 years.
measure: OS
timeFrame: From date of enrollment until the date of first documented death assessed up to 5 years.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
Study officials:
References: