Zanubrutinib Plus GCVP (Obinutuzumab, Cyclophosphamide, Vindesine, Prednisolone) in Previously Untreated Follicular Lymphoma

NCT06918015 | Not Yet Recruiting Phase 2

• 1 other identifier: ZGCVP
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

Previously untreated patients with follicular lymphoma are treated with the ZGCVP regimen (zanubrutinib, obinutuzumab, cyclophosphamide, vindesine, prednisolone) for 6 cycles.

Conditions

BTK Inhibitors; Follicular Lymphoma; Immunochemotherapy

Keywords

BTK inhibitors; follicular lymphoma; immunochemotherapy; first-line therapy

Outcome Measures

Primary Outcomes (1)

• CRR

  Complete response rate

  21days after the end of treatment

Secondary Outcomes (5)

• ORR

  21days after the end of treatment

• DOR

  the time from the date of initial assessment as complete response (CR) or partial response (PR) until the date of disease progression or death from any cause, whichever occurs first, assessed up to 24 months

• PFS

  the time from the date of initial treatment until the date of disease progression or death from any cause, whichever occurs first, assessed up to 24 months

• OS

  the time from the date of initial treatment until the date of death from any cause, assessed up to 24 months

• Disease Transformation Rate

  From the first day of treatment until histological confirmation of transformation, death, or end of study follow-up, whichever occurs first, assessed up to 24 months

Other Outcomes (1)

• AE and SAE

  from the first day of treatment until 30 days after the last treatment

Study Arms (1)

zanubrutinib, obinutuzumab, cyclophosphamide, vindesine, prednisolone

EXPERIMENTAL

Patients receive the ZGCVP regimen (zanubrutinib, obinutuzumab, cyclophosphamide, vindesine, prednisolone) for 6 cycles at the following dose: 1. Zanubrutinib: 160mg orally twice daily; 2. Obinutuzumab: 1000mg intravenously on days 1, 8, and 15 of cycle 1 and on day 1 of subsequent 5 cycles; 3. Cyclophosphamide: 750m/m2 intravenously on days 1 of every cycle; 4. Vindesine: 3 mg/m2 (maximum dose 4 mg) intravenously on days 1 of every cycle; 5. Prednisolone: 30mg orally three times daily on day 1-5 of every cycle.

Drug: ZGCVP

Interventions

ZGCVP DRUG

Patients receive the ZGCVP regimen (zanubrutinib, obinutuzumab, cyclophosphamide, vindesine, prednisolone) for 6 cycles at the following dose: 1. Zanubrutinib: 160mg orally twice daily; 2. Obinutuzumab: 1000mg intravenously on days 1, 8, and 15 of cycle 1 and on day 1 of subsequent 5 cycles; 3. Cyclophosphamide: 750m/m2 intravenously on days 1 of every cycle; 4. Vindesine: 3 mg/m2 (maximum dose 4 mg) intravenously on days 1 of every cycle; 5. Prednisolone: 30mg orally three times daily on day 1-5 of every cycle. Patients achieving CR at stage II underwent observation directly; those at stage III/IV receive obinutuzumab maintenance every 8 weeks for 2 years (1000mg intravenously) until disease progression or withdrawal. Patients with disease progression during treatment switch to second-line therapy.

Also known as: ZGCOP

zanubrutinib, obinutuzumab, cyclophosphamide, vindesine, prednisolone

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participate in the clinical study voluntarily, fully understand and be informed of the study, sign the informed consent in person, willing to follow and be able to complete all test procedures.
• years old (inclusive), all genders.
• Histopathologically confirmed grade 1-3a follicular lymphoma (FL) at stage III/IV or extensive stage II disease not suitable for radiotherapy, with at least one evaluable lesion (short axis ≥ 1.5 cm), meeting treatment indications according to GELF criteria or having a strong treatment desire.
• No prior anti-tumor therapy, such as chemotherapy, radiotherapy, immunotherapy or biotherapy (tumor vaccine, cytokine, or growth factor controlling cancer).
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-3.
• Adequate bone marrow and organ function, no serious hematopoietic dysfunction, abnormal heart, lung, liver, kidney function and immune deficiency.
• Blood routine: White blood cell count ≥ 3.0×109/L, Absolute neutrophil count ≥ 1.5×109/L (use of granulocyte colony stimulating factor is permitted), Hemoglobin ≥ 9.0 g/dL (pre-transfusion or use of recombinant human erythropoietin is permitted), Platelet count ≥ 75×109/L (transfusion is permitted to reach this level). If peripheral blood abnormalities are due to lymphoma infiltration of the bone marrow or spleen, enrollment may be considered at the investigator's discretion.
• Echocardiogram: Left ventricular ejection fraction (LVEF) ≥ 50%.
• Liver function: serum bilirubin ≤ 2.5 times the upper limit of normal value, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times the upper limit of normal value (AST is allowed if liver is involved, ALT ≤ 5 times the upper limit of normal value).
• Renal function: creatinine clearance ≥ 60 mL/min (estimated according to the Cockcroft-Gault formula).
• Coagulation function: INR ≤ 1.5 times the upper limit of normal value; PT and APTT ≤ 1.5 times the upper limit of normal value.
• Life Expectancy of at least 6 months.
• Men and women of childbearing potential must use contraception during the study and for at least 90 days after the last dose of study medication.

You may not qualify if:

• Central nervous system involvement secondary to lymphoma.
• Known severe allergic reactions to humanized or murine monoclonal antibodies, or known contraindications to any drug in the regimen.
• History of Human Immunodeficiency Virus (HIV) infection and/or other acquired Immunodeficiency syndrome. During screening period, patients with hepatitis B virus (HBV) surface antigen or hepatitis C virus (HCV) antibody positive must further test HBV DNA (no more than 2000 iu/ml) and HCV RNA (not exceed the method detection limit). Those ruling out active HBV or HCV infection are permitted to participate in the study. Carriers of the HBV, those with stable HBV after treatment or cured of HCV are also allowed to be enrolled.
• Any active infections, including but not limited to bacterial, fungal or viral infections, that require systemic anti-infective treatment within 14 days prior to initiation treatment.
• Major surgery was performed within 28 days prior to initiation treatment.
• Combined with severe or uncontrolled disease, including but not limited to congestive heart failure, uncontrolled hypertension, unstable angina, active peptic ulcer, severe hemorrhagic diseases (such as hemophilia, von willebrand disease) or spontaneous bleeding.
• History of stroke or intracranial hemorrhage within 6 months prior to initiation treatment.
• Continuous treatment with strong and moderate CYP3A inhibitors or CYP3A inducers is required.
• History of severe neurological or psychiatric disorders, including but not limited to dementia or epilepsy.
• Conditions related to drug abuse or medical, psychological and social issues that may interfere with study participation or outcome evaluation.
• Investigator Discretion: Any patient deemed unsuitable for enrollment by the investigator.
• Patients deemed unsuitable for the study by investigators.

Sponsors & Collaborators

• Zhejiang Cancer Hospital: lead

Study Sites (1)

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310058, China

Location

MeSH Terms

Conditions

Lymphoma, Follicular

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Haiyan Yang, MD

  Zhejiang Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Haiyan Yang, MD

CONTACT

86-0571-88122192; yanghy@zjcc.org.cn

Haifeng Yu, MD

CONTACT

86-0571-88122192; yuhaifeng5533@dingtalk.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: March 20, 2025
• First Posted: April 9, 2025
• Study Start: May 1, 2025
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2030
• Last Updated: April 15, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)