Follicular LymphomaPhase 2ZGR in TN FLNCT07299149
Zanubrutinib, Obinutuzumab Combined With Lenalidomide (ZGR) for the Treatment of Untreated Follicular Lymphoma
A Phase 2 study testing Induction Therapy: Zanubrutinib, obinutuzumab, lenalidomide and Maintenance therapy: Zanubrutinib, lenalidomide in people with Follicular Lymphoma, run by Institute of Hematology & Blood Diseases Hospital, China at 2 sites in China.
Trial summary
This study is planned to prospectively evaluates the efficacy and safety of the zanubrutinib, obinutuzumab, and lenalidomide (ZGR) combination regimen in treatment-naïve follicular lymphoma (FL) patients in a Chinese population. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Follicular Lymphoma
- What is being tested?
- Induction Therapy: Zanubrutinib, obinutuzumab, lenalidomide and Maintenance therapy: Zanubrutinib, lenalidomide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 2 sitesChina
- Study dates
- 25 Dec 2025to 25 Dec 2030
- 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 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Gender: No restrictions; age ≥18 years.
- Diagnosis: Histologically confirmed CD20-positive follicular lymphoma (FL), Grade 1, 2, or 3A, per 2016 WHO classification. All patients must provide sufficient archived or fresh tumor tissue samples for immunohistochemical (IHC) analysis.
- Disease Stage \& Treatment Need:
- Stage III or IV disease, or Stage II with bulky disease, meeting at least one of the following criteria:
- a) Bulky disease: Lymph node or extranodal (excluding spleen) mass with maximum diameter ≥7 cm.
- b) Local symptoms or organ dysfunction due to progressive lymphadenopathy or extranodal tumor mass.
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- c) B symptoms (fever, night sweats, or unintentional weight loss >10% of body weight within ≤6 months).
- d) Symptomatic extranodal involvement (e.g., pleural/peritoneal effusion).
- e) Cytopenias due to bone marrow infiltration (hemoglobin <10 g/dL, absolute neutrophil count [ANC] <1.0×10⁹/L, platelets <100×10⁹/L).
- f) Involvement of ≥3 lymph nodes, each ≥3 cm in diameter.
- g) Symptomatic splenomegaly.
- Prior Therapy: No prior systemic therapy for FL.
- ECOG Performance Status: ≤2.
- Measurable Disease: At least one measurable lesion (>2 cm in longest diameter by CT/MRI).
- Life Expectancy: ≥6 months.
- Adequate Organ Function:
- a) ANC ≥1.0×10⁹/L (without growth factor support).
- b) Platelets ≥50×10⁹/L (untransfused within 7 days).
- c) Total bilirubin (TBIL) ≤1.5×ULN.
- d) ALT/AST ≤3×ULN.
- e) Creatinine clearance ≥30 mL/min (calculated by modified Cockcroft-Gault formula).
- Contraception: Men and women of childbearing potential must agree to use highly effective contraception during the study and for 4 weeks after treatment discontinuation.
- Informed Consent: Patients must voluntarily participate and sign informed consent forms (ICF).
Who cannot join
- Patients meeting any of the following criteria will be excluded from this study:
- Histologic evidence of central nervous system (CNS) lymphoma, leptomeningeal lymphoma, or transformation to high-grade lymphoma (e.g., diffuse large B-cell lymphoma, DLBCL).
- Grade 3B follicular lymphoma (FL) or transformed FL.
- Ann Arbor Stage I FL.
- Prior history of malignancy, unless the patient has been disease-free for ≥5 years and the treating physician deems the risk of recurrence low (exceptions: non-melanoma skin cancer, cured localized prostate cancer, carcinoma in situ of the cervix, or squamous intraepithelial lesions on PAP smear).
- Use of any investigational drugs, antibiotics, or participation in another interventional clinical trial within 4 weeks prior to enrollment.
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- Major surgery (excluding lymph node biopsy) within 14 days before enrollment or anticipated need for major surgery during the study.
- Prior treatment with zanubrutinib, obinutuzumab, or lenalidomide.
- Immunodeficiency or autoimmune disease history, or chronic systemic steroid therapy (>10 mg/day prednisone equivalent) or immunosuppressive therapy within 7 days before enrollment.
- Severe hepatic dysfunction (including severe jaundice, hepatic encephalopathy, refractory ascites, or hepatorenal syndrome), cachexia, or multi-organ failure with renal impairment.
- Clinically significant cardiovascular abnormalities:
- NYHA Class III/IV heart failure
- Myocardial infarction within 6 months before enrollment, Malignant arrhythmias (including QTc ≥480 ms), Uncontrolled hypertension (Systolic blood pressure (SBP) ≥150 mmHg and diastolic blood pressure (DBP) ≥100 mmHg), Unstable angina.
- Active infections:
- HIV, active hepatitis B/C infection (HBV DNA ≥2000 IU/mL or HCV RNA detectable)
- Uncontrolled systemic infections.
- Bleeding disorders or coagulation abnormalities, or thrombotic events within 3 months.
- Severe hypersensitivity to the active ingredients or excipients of the study drugs.
- Pregnancy, lactation, or unwillingness to use effective contraception in women of childbearing potential.
- Other conditions deemed unsuitable by the investigator.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China2 sites, 2 recruiting
- Not yet recruiting
Institute of Hematology and Blood Diseases Hospital ,Chinese Academy of Medical Sciences, Tianjin, Tianjin 300020
Tianjin, Tianjin Municipality, 300020
Rui Lyu, 02223909095, ec@ihcams.ac.cn
- Recruiting
Institute of Hematology and Blood Diseases Hospital ,Chinese Academy of Medical Sciences
Tianjin, Tianjin Municipality, 300020
Yuting Yan, 13820706239, yanyuting@ihcams.ac.cn
About this study
Official title: A Prospective, Open-label, Single-arm Multicenter Clinical Study of Zanubrutinib, Obinutuzumab, and Lenalidomide (ZGR) in the Treatment of Untreated Follicular Lymphoma
This study is planned to prospectively evaluates the efficacy and safety of the zanubrutinib, obinutuzumab, and lenalidomide (ZGR) combination regimen in treatment-naïve follicular lymphoma (FL) patients in a Chinese population.
Read the detailed description
Regarding chemotherapy-free first-line treatment regimens, current targeted therapies primarily focus on lenalidomide combined with anti-CD20 antibodies. Chemotherapy-free regimens such as rituximab plus lenalidomide (R²) or obinutuzumab plus lenalidomide (O-Len) have been recommended for clinical use. Encouraged by the promising efficacy of dual-targeted therapies, the potential of triple-combination therapy-comprising a BTK inhibitor (BTKi), an anti-CD20 monoclonal antibody, and lenalidomide-has garnered increasing attention in untreated hematologic malignancies. Most existing studies have concentrated on BTKi combined with rituximab and lenalidomide (e.g., ibrutinib + R²).
Given current clinical needs and available evidence, this study aims to explore a novel chemotherapy-free triple regimen: zanubrutinib combined with obinutuzumab and lenalidomide (ZGR) in treatment-naïve follicular lymphoma (FL) patients. This combination is expected to provide a new treatment paradigm for untreated FL, offering high antitumor efficacy while minimizing toxicity, thereby improving patients' quality of life.
- Conditions
- Follicular Lymphoma
- Being tested
- Induction Therapy: Zanubrutinib, obinutuzumab, lenalidomide, Maintenance therapy: Zanubrutinib, lenalidomide
- Keywords
- follicular lymphoma, zanubrutinib, Obinutuzumab, lenalidomide
- Medical subject headings
- Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Induction Therapy: Zanubrutinib, obinutuzumab, lenalidomideDrug
All enrolled patients received: Zanubrutinib: 160 mg twice daily, orally, on Days 1-28; Obinutuzumab: 1000 mg, intravenous infusion: Days 1, 8, and 15 of Cycle 1,on Day 1 of Cycles 2-6; Lenalidomide: 25 mg once daily, orally, on Days 1-21 of each 28-day cycle.
Maintenance therapy: Zanubrutinib, lenalidomideDrug
Maintenance therapy consists of zanubrutinib plus lenalidomide: Zanubrutinib: 160 mg twice daily, orally, on Days 1-28.Lenalidomide: 25 mg every other day, orally, on Days 1-21 of each 28-day cycle
| Study group | Role | What they receive |
|---|---|---|
| Experimental: Induction therapy of ZGR, and maintenance therapy of ZR | Experimental | Induction therapy: All enrolled patients received the ZGR regimen (zanubrutinib, obinutuzumab, and lenalidomide) for Cycles 1-4. Tumor response was assessed after Cycle 4. Patients achieving complete response (CR) or partial response (PR) continued the same ZGR regimen for 2 additional cycles (Cycles 5-6).
Maintenance therapy: After completing induction therapy, patients with sustained CR/PR initiated maintenance therapy with zanubrutinib plus lenalidomide (ZR) for 18 months (1.5 years) or until disease progression, intolerable toxicity, or trial withdrawal (whichever occurred first) Receives: Drug: Induction Therapy: Zanubrutinib, obinutuzumab, lenalidomide; Drug: Maintenance therapy: Zanubrutinib, lenalidomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate，ORR
Defined as the proportion of patients with complete or partial response as assessed by response to induction therapy
Measured: up to the end of 6 cycles of treatment(each cycle is 28 days)]
Secondary outcomes (9)
Complete response rate，CRR
defined as the proportion of patients with complete response as assessed by response to induction therapy.
Measured: up to the end of 6 cycles of treatment(each cycle is 28 days)
Best overall response rate (ORR) and complete response rate (CRR) during treatment
defined as the proportion of patients with best response as assessed in the induction therapy.
Measured: Up to the end of 6 cycles of treatment(each cycle is 28 days)
CRR and ORR at end of treatment
Defined as the proportion of patients with complete response, and complete or partial response as assessed by response to the end of treatment(induction + maintenance therapy)
Measured: at the end of Cycle 24 (each cycle is 28 days)
Progression-free survival (PFS)
The time from the enrollment of a subject to the occurrence of (in any way) progression of disease or Death for any reason. patients with indeterminate recurrence or Death at the last follow-up, defined as the date of the last Investigation
Measured: up to 5 years
Duration of response (DOR)
defined as the time from the first treatment response (including complete response and partial response) to the last assessment of response.
Measured: up to 5 years
Time to response (TTR)
Measured: at the end of Cycle 24 (each cycle is 28 days)
2-year overall survival (OS) rate
The time from subject enrollment to Death caused by any reason. for patients lost to follow-up, the time of the last follow-up; for patients still alive at the end of study, the date of the end of follow-up
Measured: up to 2 years
Proportion of patients with progression of disease within 24 months (POD24)
Measured: Up to the end of 2 years (each cycle is 28 days)
The safety
Incidence of adverse events, serious adverse events and significant adverse event
Measured: 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 posted23 Dec 2025
- Study start25 Dec 2025
- Primary completion28 Apr 2028 (estimated)
- Study completion25 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Follicular LymphomaStudies of the same condition, open and under way.
- More trials run by Institute of Hematology & Blood Diseases Hospital, ChinaThe 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
- 34 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Shuhua Yi, Principal investigator, Institute of Hematology & Blood Diseases Hospital, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07299149
- Sponsor's protocol ID
- IIT2025107
- Acronym
- ZGR in TN FL
- Status last verified
- May 2026
- First submitted
- 21 Nov 2025
- Last updated
- 13 May 2026
- Results posted
- 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 13 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Open-label, Single-arm Multicenter Clinical Study of Zanubrutinib, Obinutuzumab, and Lenalidomide (ZGR) in the Treatment of Untreated Follicular Lymphoma
- ClinicalTrials.gov ID
- NCT07299149
- Acronym / sponsor ID
- ZGR in TN FL / IIT2025107
- Conditions
- Follicular Lymphoma
- Keywords
- follicular lymphoma, zanubrutinib, Obinutuzumab, lenalidomide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- Institute of Hematology & Blood Diseases Hospital, ChinaUniversity, hospital or other
- Study start
- 25 Dec 2025 (actual)
- Primary completion
- 28 Apr 2028 (estimated)
- Study completion
- 25 Dec 2030 (estimated)
- First posted
- 23 Dec 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.
This study is planned to prospectively evaluates the efficacy and safety of the zanubrutinib, obinutuzumab, and lenalidomide (ZGR) combination regimen in treatment-naïve follicular lymphoma (FL) patients in a Chinese population.
Detailed description
Regarding chemotherapy-free first-line treatment regimens, current targeted therapies primarily focus on lenalidomide combined with anti-CD20 antibodies. Chemotherapy-free regimens such as rituximab plus lenalidomide (R²) or obinutuzumab plus lenalidomide (O-Len) have been recommended for clinical use. Encouraged by the promising efficacy of dual-targeted therapies, the potential of triple-combination therapy-comprising a BTK inhibitor (BTKi), an anti-CD20 monoclonal antibody, and lenalidomide-has garnered increasing attention in untreated hematologic malignancies. Most existing studies have concentrated on BTKi combined with rituximab and lenalidomide (e.g., ibrutinib + R²).
Given current clinical needs and available evidence, this study aims to explore a novel chemotherapy-free triple regimen: zanubrutinib combined with obinutuzumab and lenalidomide (ZGR) in treatment-naïve follicular lymphoma (FL) patients. This combination is expected to provide a new treatment paradigm for untreated FL, offering high antitumor efficacy while minimizing toxicity, thereby improving patients' quality of life.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental: Induction therapy of ZGR, and maintenance therapy of ZR | Experimental | Drug: Induction Therapy: Zanubrutinib, obinutuzumab, lenalidomide, Drug: Maintenance therapy: Zanubrutinib, lenalidomideInduction therapy: All enrolled patients received the ZGR regimen (zanubrutinib, obinutuzumab, and lenalidomide) for Cycles 1-4. Tumor response was assessed after Cycle 4. Patients achieving complete response (CR) or partial response (PR) continued the same ZGR regimen for 2 additional cycles (Cycles 5-6). Maintenance therapy: After completing induction therapy, patients with sustained CR/PR initiated maintenance therapy with zanubrutinib plus lenalidomide (ZR) for 18 months (1.5 years) or until disease progression, intolerable toxicity, or trial withdrawal (whichever occurred first) |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Gender: No restrictions; age ≥18 years.
- Diagnosis: Histologically confirmed CD20-positive follicular lymphoma (FL), Grade 1, 2, or 3A, per 2016 WHO classification. All patients must provide sufficient archived or fresh tumor tissue samples for immunohistochemical (IHC) analysis.
- Disease Stage \& Treatment Need:
- Stage III or IV disease, or Stage II with bulky disease, meeting at least one of the following criteria:
- a) Bulky disease: Lymph node or extranodal (excluding spleen) mass with maximum diameter ≥7 cm.
Key exclusion criteria (20 listed)
- Patients meeting any of the following criteria will be excluded from this study:
- Histologic evidence of central nervous system (CNS) lymphoma, leptomeningeal lymphoma, or transformation to high-grade lymphoma (e.g., diffuse large B-cell lymphoma, DLBCL).
- Grade 3B follicular lymphoma (FL) or transformed FL.
- Ann Arbor Stage I FL.
- Prior history of malignancy, unless the patient has been disease-free for ≥5 years and the treating physician deems the risk of recurrence low (exceptions: non-melanoma skin cancer, cured localized prostate cancer, carcinoma in situ of the cervix, or squamous intraepithelial lesions on PAP smear).
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 |
|---|---|---|
| Induction Therapy: Zanubrutinib, obinutuzumab, lenalidomideAll enrolled patients received: Zanubrutinib: 160 mg twice daily, orally, on Days 1-28; Obinutuzumab: 1000 mg, intravenous infusion: Days 1, 8, and 15 of Cycle 1,on Day 1 of Cycles 2-6; Lenalidomide: 25 mg once daily, orally, on Days 1-21 of each 28-day cycle. | Drug | Experimental: Induction therapy of ZGR, and maintenance therapy of ZR |
| Maintenance therapy: Zanubrutinib, lenalidomideMaintenance therapy consists of zanubrutinib plus lenalidomide: Zanubrutinib: 160 mg twice daily, orally, on Days 1-28.Lenalidomide: 25 mg every other day, orally, on Days 1-21 of each 28-day cycle | Drug | Experimental: Induction therapy of ZGR, and maintenance therapy of ZR |
Primary outcome
Objective response rate，ORR
Time frame: up to the end of 6 cycles of treatment(each cycle is 28 days)]
Defined as the proportion of patients with complete or partial response as assessed by response to induction therapy
9 secondary outcomes
Complete response rate，CRR
Time frame: up to the end of 6 cycles of treatment(each cycle is 28 days)
Best overall response rate (ORR) and complete response rate (CRR) during treatment
Time frame: Up to the end of 6 cycles of treatment(each cycle is 28 days)
CRR and ORR at end of treatment
Time frame: at the end of Cycle 24 (each cycle is 28 days)
Progression-free survival (PFS)
Time frame: up to 5 years
Duration of response (DOR)
Time frame: up to 5 years
Time to response (TTR)
Time frame: at the end of Cycle 24 (each cycle is 28 days)
2-year overall survival (OS) rate
Time frame: up to 2 years
Proportion of patients with progression of disease within 24 months (POD24)
Time frame: Up to the end of 2 years (each cycle is 28 days)
The safety
Time frame: 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 13 May 2026.
- 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.
Shuhua Yi principal investigator
Institute of Hematology & Blood Diseases Hospital, China
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Induction Therapy: Zanubrutinib, obinutuzumab, lenalidomide and Maintenance therapy: Zanubrutinib, lenalidomide in people with Follicular Lymphoma, run by Institute of Hematology & Blood Diseases Hospital, China at 2 sites 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 23 inclusion and 20 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 13 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 Shuhua Yi, Dr (+86-022-23909106, yishuhua@ihcams.ac.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate，ORR (time frame: up to the end of 6 cycles of treatment(each cycle is 28 days)]). 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 13 May 2026.