NCT06959732

Zanubrutinib Combined With G-CVP in Previously Untreated FL

Efficacy and Safety of Zanubrutinib Combined With G-CVP Regimen in Previously Untreated Follicular Lymphoma

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Follicular Lymphoma ( FL)

Interventions

Type	Name	Description
DRUG	zanubrutinib, obinutuzumab,combined with CVP	Zanubrutinib (160 mg, twice daily \[bid\]), obinutuzumab (1000 mg on cycle 1 \[C1\], days 1, 8, and 15; on cycle 2 - 6 \[C 2-6\], day 1), cyclophosphamide (750 mg/㎡ on day 1), vincristine (1.4 mg/㎡, maximum dose 2 mg on day 1), and prednisone tablets (40 mg/㎡ once daily \[qd\] orally on days 1-5) were used every 21 days as a treatment cycle. Six cycles of treatment were completed, and the efficacy was reviewed every two cycles. Patients with PD were excluded from the group. MRD was detected after six cycles. If MRD was negative, routine maintenance therapy was performed (obinutuzumab 1000 mg once every 8 weeks, a total of 12 times). If MRD was positive, Zanubrutinib (160 mg, continuous bid) was added to the conventional maintenance therapy for 12 months.

Timeline

• Start date: 2025-01-01
• Primary completion: 2027-06-30
• Completion: 2027-12-31
• First posted: 2025-05-07
• Last updated: 2025-05-07

Locations

1 site across 1 country: China