Zanubrutinib Combined With G-CVP in Previously Untreated FL

Last updated: May 4, 2025
Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Overall Status: Active - Recruiting

Phase

2

Condition

Lymphoma

Follicular Lymphoma

Treatment

zanubrutinib, obinutuzumab,combined with CVP

Clinical Study ID

NCT06959732
24/548-4828
  • Ages 18-80
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

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 accordingto the WHO 2022 criteria; 2, Clear indication for treatment: symptoms affectingnormal work and life; end-organ dysfunction; cytopenia due to bone marrowinvolvement by lymphoma; bulky disease (per GELF criteria); persistent or rapidlyprogressive disease; 3. No prior systemic therapy for lymphoma; 4. Age 18-80 years;
  2. Eastern cooperative oncology group (ECOG) performance status (PS) < 2; 6.Expected survival > 2 years; 7. At least one measurable lesion with a longestdiameter ≥ 1.5 cm or extranodal lesion ≥ 1 cm; 8. Willingness to participate in thestudy and comply with treatment and follow-up.

Exclusion

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 serumcreatinine > 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 12months;

  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, cervicalcarcinoma in situ, localized prostate cancer, superficial bladder cancer, ductalcarcinoma 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 withstudy participation or result evaluation;

  10. Investigator-deemed ineligibility for the study.

Study Design

Total Participants: 40
Treatment Group(s): 1
Primary Treatment: zanubrutinib, obinutuzumab,combined with CVP
Phase: 2
Study Start date:
January 01, 2025
Estimated Completion Date:
December 31, 2027

Study 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.

Connect with a study center

  • Cancer Hospital Chinese Academy of Medical Sciences

    Beijing, Beijing 100021
    China

    Active - Recruiting

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