Follicular Lymphoma ( FL)Phase 2NCT06959732
Zanubrutinib Combined With G-CVP in Previously Untreated FL
A Phase 2 study testing zanubrutinib, obinutuzumab,combined with CVP in people with Follicular Lymphoma ( FL), run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Follicular Lymphoma ( FL)
- What is being tested?
- zanubrutinib, obinutuzumab,combined with CVP
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteChina
- Study dates
- 1 Jan 2025to 31 Dec 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Patients will be excluded if they meet any of the following criteria:
- Pregnant or breastfeeding women;
- 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);
- History of deep vein thrombosis (DVT) or pulmonary embolism (PE) within the past 12 months;
- 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);
- Long-term use of strong or moderate CYP3A inducers;
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- Known hypersensitivity to any component of the study drug;
- 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;
- Severe concurrent infections;
- Drug abuse, medical, psychological, or social conditions that may interfere with study participation or result evaluation;
- Investigator-deemed ineligibility for the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Cancer Hospital Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, 100021
Zhitao Ying, 008613811818096, yingzhitao001@163.com
About this study
Official title: Efficacy and Safety of Zanubrutinib Combined With G-CVP Regimen in Previously Untreated Follicular Lymphoma
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.
Read the 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)
- Being tested
- zanubrutinib, obinutuzumab,combined with CVP
- Keywords
- Follicular Lymphoma ( FL), Zanubrutinib, Obinutuzumab, CVP
- Medical subject headings
- Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
zanubrutinib, obinutuzumab,combined with CVPDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| ZG- CVP | Experimental | Zanubrutinib , obinutuzumab , cyclophosphamide , vincristine, and prednisone tablets 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 progressive disease (PD) were excluded from the group. MRD was detected after six cycles. If MRD was negative, routine maintenance therapy was performed . If MRD was positive, Zanubrutinib was added to the conventional maintenance therapy for 12 months. Receives: Drug: zanubrutinib, obinutuzumab,combined with CVP |
What is being measured
The primary outcome is the main question the study is designed to answer.
CRR
CRR (%) is defined as the number of patients achieving a complete response as a proportion of total patients evaluable for response.
Measured: From date of enrollment until the date of first documented CR assessed up to 2.5 years.
Secondary outcomes (3)
ORR
ORR (%) is defined as the number of patients achieving a complete response or partial response as a proportion of total patients evaluable for response.
Measured: From date of enrollment until the date of first documented response assessed up to 2.5 years.
PFS
PFS is defined as the time interval from the time of enrollment on this study to the date of PD or death, whichever came first.
Measured: From date of enrollment until the date of first documented progression assessed up to 5 years.
OS
OS is defined as the time interval from the time of enrollment in this study to the date of death from any cause. If the subject is alive or the vital status is unknown, OS will be censored at the date that the subject is last known to be alive, or their last contact date.
Measured: From date of enrollment until the date of first documented death assessed up to 5 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2025
- Study start1 Jan 2025
- Primary completion30 Jun 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Follicular Lymphoma ( FL)Studies of the same condition, open and under way.
- More trials run by Cancer Institute and Hospital, Chinese Academy of Medical SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhitao Ying, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06959732
- Sponsor's protocol ID
- 24/548-4828
- Status last verified
- May 2025
- First submitted
- 25 Apr 2025
- Last updated
- 7 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Zanubrutinib Combined With G-CVP Regimen in Previously Untreated Follicular Lymphoma
- ClinicalTrials.gov ID
- NCT06959732
- Acronym / sponsor ID
- 24/548-4828
- Conditions
- Follicular Lymphoma ( FL)
- Keywords
- Follicular Lymphoma ( FL), Zanubrutinib, Obinutuzumab, CVP
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Cancer Institute and Hospital, Chinese Academy of Medical SciencesUniversity, hospital or other
- Study start
- 1 Jan 2025 (actual)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 7 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ZG- CVP | Experimental | Drug: zanubrutinib, obinutuzumab,combined with CVPZanubrutinib , obinutuzumab , cyclophosphamide , vincristine, and prednisone tablets 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 progressive disease (PD) were excluded from the group. MRD was detected after six cycles. If MRD was negative, routine maintenance therapy was performed . If MRD was positive, Zanubrutinib was added to the conventional maintenance therapy for 12 months. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (11 listed)
- Pregnant or breastfeeding women;
- 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);
- History of deep vein thrombosis (DVT) or pulmonary embolism (PE) within the past 12 months;
- 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);
- Long-term use of strong or moderate CYP3A inducers;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| zanubrutinib, obinutuzumab,combined with CVPZanubrutinib (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. | Drug | ZG- CVP |
Primary outcome
CRR
Time frame: From date of enrollment until the date of first documented CR assessed up to 2.5 years.
CRR (%) is defined as the number of patients achieving a complete response as a proportion of total patients evaluable for response.
3 secondary outcomes
ORR
Time frame: From date of enrollment until the date of first documented response assessed up to 2.5 years.
PFS
Time frame: From date of enrollment until the date of first documented progression assessed up to 5 years.
OS
Time frame: From date of enrollment until the date of first documented death assessed up to 5 years.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing zanubrutinib, obinutuzumab,combined with CVP in people with Follicular Lymphoma ( FL), run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 7 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Zhitao Ying (008613811818096, yingzhitao001@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CRR (time frame: From date of enrollment until the date of first documented CR assessed up to 2.5 years.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2025.