Relapsed/Refractory Follicular LymphomaPhase 2NCT07418190
Efficacy and Safety of Zanubrutinib, Rituximab, and Lenalidomide (ZR²) in Combination With Tislelizumab for Relapsed/Refractory Follicular Lymphoma
A Phase 2 study testing tislelizumab + zanubrutinib + rituximab + lenalidomide in people with Relapsed/Refractory Follicular Lymphoma, run by The First Affiliated Hospital with Nanjing Medical University at 1 site in China.
Trial summary
This is a prospective, open-label, single-arm, single-center, Phase II clinical study designed to evaluate the efficacy and safety of zanubrutinib, rituximab, and lenalidomide (ZR²) in combination with tislelizumab in patients with relapsed/refractory follicular lymphoma who have relapsed or are refractory after ≥1… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Relapsed/Refractory Follicular Lymphoma
- What is being tested?
- tislelizumab + zanubrutinib + rituximab + 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
- 33 participants
- Where
- 1 siteChina
- Study dates
- 1 Feb 2026to 31 Dec 2029
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Eligible participants must meet all of the following criteria:
- Provide written informed consent. Age ≥18 years . Histologically confirmed relapsed/refractory follicular lymphoma (R/R FL) . Received at least two prior lines of systemic therapy , including anti-CD20 monoclonal antibody therapy.
- ECOG performance status 0-1 . Measurable disease , with longest diameter >1.5 cm . Estimated life expectancy (per investigator assessment) ≥18 weeks . Adverse events from prior anticancer therapy must have resolved to ≤ grade 1 (except alopecia and anorexia).
- Adequate hepatic function:
- Total bilirubin ≤1.5 × ULN ; for patients with documented Gilbert syndrome: total bilirubin ≤3 × ULN with predominantly indirect hyperbilirubinemia.
- AST and ALT ≤3 × ULN .
Show all 10Show fewer
- Adequate hematologic function:
- ANC ≥1.5 × 10⁹/L (≥1,500/µL) Platelets ≥75,000/µL , with no platelet transfusion within 14 days prior to first dosing on Cycle 1 Day 1 Hemoglobin ≥10.0 g/dL (6.2 mmol/L), with no blood transfusion within 21 days prior to first dosing on Cycle 1 Day 1 Adequate renal function: serum creatinine ≤1.5 × ULN , or creatinine clearance ≥50 mL/min calculated by the Cockcroft-Gault formula (see Appendix 14), for patients in whom serum creatinine may not adequately reflect renal function per investigator judgment.
- For women of childbearing potential: negative serum pregnancy test within 7 days before study treatment; postmenopausal women (non-treatment-related amenorrhea ≥12 months) or surgically sterile women (no ovaries and/or uterus) are exempt. Women of childbearing potential must agree to abstinence (avoid heterosexual intercourse) or to use effective contraception.
- For men: agree to abstinence (avoid heterosexual intercourse) or to use effective contraception.
Who cannot join
- Participants meeting any of the following will be excluded:
- Unable to comply with protocol-required hospitalization and restrictions.
- Active infection or latent tuberculosis infection.
- History of severe hypersensitivity to drugs of the same class.
- Current central nervous system involvement.
- Pregnant or breastfeeding women.
Show all 17Show fewer
- Uncontrolled comorbidities (e.g., cardiac disease, immune disorders); myocardial infarction, unstable arrhythmia, or unstable angina within the past 6 months.
- Illicit drug use or alcohol abuse within 12 months prior to screening, per investigator judgment.
- Any other disease, metabolic disorder, physical examination finding, or clinical laboratory abnormality that reasonably suggests a contraindication to the investigational products.
- The investigator should review vaccination status of potential participants and, prior to study initiation, follow local disease control and prevention guidelines for adult immunization with non-live vaccines aimed at preventing infectious diseases.
- Any psychiatric or cognitive disorder that may limit understanding/execution of informed consent or protocol compliance.
- Pregnant or breastfeeding women, or women/men (or male partners) planning pregnancy during the study period.
- Any other condition deemed by the investigator to make the participant unsuitable for the trial.
- Cases to Be Excluded From Statistical Analysis (per protocol)
- Participants already enrolled who meet any of the following will be treated as excluded cases in statistical analyses:
- Post-enrollment discovery of non-fulfillment of eligibility criteria. Prior exposure to zanubrutinib or other BTK inhibitors. Intolerable toxicity after taking zanubrutinib or other BTK inhibitors. Received fewer than two consecutive administrations after enrollment such that objective efficacy cannot be assessed (adverse events may still be assessable).
- Protocol violations. Prior hematopoietic stem cell transplantation.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Wei Xu, PhD contact
China1 site, 1 recruiting
- Recruiting
Jiangsu Province Hospital
Nanjing, Jiangsu, 210000
Jinhua Liang, PhD, 15952032421, 1151525490@qq.com
Wei Xu, xuwei10000@hotmail.com
About this study
This is a prospective, open-label, single-arm, single-center, Phase II clinical study designed to evaluate the efficacy and safety of zanubrutinib, rituximab, and lenalidomide (ZR²) in combination with tislelizumab in patients with relapsed/refractory follicular lymphoma who have relapsed or are refractory after ≥1 prior systemic therapy.
After successful screening, enrolled patients will receive 6 treatment cycles (21 days per cycle). Disease response will be assessed by CT/PET-CT during treatment and after completion of induction. Patients who achieve CR/PR/SD will proceed to the maintenance phase; patients who do not achieve at least SD (i.e., fail to reach CR/PR/SD) during induction will discontinue the study. Patients with CR/PR/SD after induction will receive maintenance therapy with zanubrutinib plus tislelizumab until disease progression, unacceptable toxicity, or completion of 1 year of maintenance.
Efficacy and safety assessments will be performed per protocol. Tumor response will be assessed by site investigators according to the 2014 Lugano criteria, including determination of response status, date of response, and date of progression/relapse.
- Conditions
- Relapsed/Refractory Follicular Lymphoma
- Being tested
- tislelizumab + zanubrutinib + rituximab + 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.
tislelizumab + zanubrutinib + rituximab + lenalidomideDrug
Patients with FL will receive a PD-1 + ZR² regimen (tislelizumab + zanubrutinib + rituximab + lenalidomide) for 6 cycles (3 weeks per cycle).
Induction Phase (Cycles 1-6; 21 days per cycle) Zanubrutinib (Z): 160 mg orally twice daily (BID). Rituximab (R): 375 mg administered intravenously on Day 1 of cycles 1-6; additionally administered on Day 1 of cycles 2-8/12 per protocol (21-day cycles).
Lenalidomide: 20 mg orally once daily on cycles 1-6. Tislelizumab: 200 mg intravenous infusion on Day 1 every 3 weeks. After 6 cycles of the four-drug combination, response will be assessed by CT/PET-CT. Patients achieving CR/PR/SD will proceed to maintenance; those not achieving at least SD will discontinue the study.
Maintenance Phase
Patients achieving CR/PR/SD during induction will receive:
Zanubrutinib: 160 mg orally BID; and Tislelizumab: 200 mg IV on Day 1 every 3 weeks until disease progression, unacceptable toxicity, or completion of 1 year of maintenance.
| Study group | Role | What they receive |
|---|---|---|
| PD-1+ZR2 | Experimental | Not described Receives: Drug: tislelizumab + zanubrutinib + rituximab + lenalidomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete response rate (CRR)
The proportion of evaluable participants who achieve complete response (CR) following 6 cycles of induction therapy. CR is defined in accordance with the 2014 Lugano Classification for Lymphoma: this requires the complete disappearance of all measurable/evaluable lymphoma lesions, resolution of all disease-related clinical symptoms, and normalization of imaging findings (e.g., no residual measurable disease on CT/MRI, and no metabolically active disease on FDG-PET/CT). The analysis population is restricted to participants who complete at least 4 cycles of induction therapy and have available post-treatment efficacy assessment data.
Measured: Within 21 days after the completion of the 6th cycle of induction therapy (Each cycle is 21 days)
Secondary outcomes (4)
Objective response rate (ORR)
The proportion of evaluable participants who achieve objective response (defined as complete response [CR] or partial response [PR]) following 6 cycles of induction therapy. Response assessment adheres to the 2014 Lugano Classification for Lymphoma: PR requires a ≥50% reduction in the sum of the longest diameters of measurable lesions, with no new lesions or progression of existing non-measurable disease. The analysis population includes participants who complete at least 4 induction cycles and have available post-treatment efficacy evaluation data.
Measured: Within 21 days after the completion of the 6th cycle of induction therapy At the end of Cycle 1 (each cycle is 21 days)
2-Year Progression-Free Survival (PFS)
The duration from randomization to the first occurrence of disease progression (per the 2014 Lugano Classification) or death from any cause. PFS will be estimated using the Kaplan-Meier method, and between-arm comparisons will be conducted via the log-rank test. Participants without progression or death at the end of follow-up will be censored at their last documented disease-evaluation date.
Measured: Up to 2 years after Start treatment
2-Year Overall Survival (OS)
The duration from randomization to death from any cause. OS will be estimated using the Kaplan-Meier method, with between-arm comparisons performed using the log-rank test. Participants who remain alive at the 2-year follow-up endpoint will be censored at their last confirmed survival date.
Measured: Up to 2 years after start treatment
Incidence of Treatment-Related Adverse Events (TRAE)
The proportion of participants experiencing any treatment-related adverse event, graded per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0. This includes the incidence of grade 3-4 TRAEs and serious adverse events (SAEs; defined as events that are life-threatening, require hospitalization, result in persistent disability, or are fatal).
Measured: From the first dose of study intervention to 30 days after the last dose of study intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2026
- Study start1 Feb 2026 (estimated)
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed/Refractory Follicular LymphomaStudies of the same condition, open and under way.
- More trials run by The First Affiliated Hospital with Nanjing Medical UniversityThe 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
- Model description
- A prospective, open-label, single-arm, single-center Phase II study in R/R FL after ≥1 prior systemic therapy. Patients receive 6 induction cycles (21 days per cycle), followed by response-based maintenance with zanubrutinib plus tislelizumab for up to 1 year or until progression/unacceptable toxicity.
- Masking
- None (open label)
- Enrolment
- 33 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Wei Xu, PhD, Principal investigator, Hematological Department, Jiangsu Province Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07418190
- Sponsor's protocol ID
- 2025-SR-921
- Status last verified
- Jan 2026
- First submitted
- 20 Jan 2026
- Last updated
- 18 Feb 2026
- 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 18 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Zanubrutinib, Rituximab, and Lenalidomide (ZR²) in Combination With Tislelizumab for Relapsed/Refractory Follicular Lymphoma
- ClinicalTrials.gov ID
- NCT07418190
- Acronym / sponsor ID
- 2025-SR-921
- Conditions
- Relapsed/Refractory Follicular Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 33 participants (estimated)
- Lead sponsor
- The First Affiliated Hospital with Nanjing Medical UniversityUniversity, hospital or other
- Study start
- 1 Feb 2026 (estimated)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 18 Feb 2026 (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 is a prospective, open-label, single-arm, single-center, Phase II clinical study designed to evaluate the efficacy and safety of zanubrutinib, rituximab, and lenalidomide (ZR²) in combination with tislelizumab in patients with relapsed/refractory follicular lymphoma who have relapsed or are refractory after ≥1 prior systemic therapy.
After successful screening, enrolled patients will receive 6 treatment cycles (21 days per cycle). Disease response will be assessed by CT/PET-CT during treatment and after completion of induction. Patients who achieve CR/PR/SD will proceed to the maintenance phase; patients who do not achieve at least SD (i.e., fail to reach CR/PR/SD) during induction will discontinue the study. Patients with CR/PR/SD after induction will receive maintenance therapy with zanubrutinib plus tislelizumab until disease progression, unacceptable toxicity, or completion of 1 year of maintenance.
Efficacy and safety assessments will be performed per protocol. Tumor response will be assessed by site investigators according to the 2014 Lugano criteria, including determination of response status, date of response, and date of progression/relapse.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- A prospective, open-label, single-arm, single-center Phase II study in R/R FL after ≥1 prior systemic therapy. Patients receive 6 induction cycles (21 days per cycle), followed by response-based maintenance with zanubrutinib plus tislelizumab for up to 1 year or until progression/unacceptable toxicity.
| Arm | Type | Receives |
|---|---|---|
| PD-1+ZR2 | Experimental | Drug: tislelizumab + zanubrutinib + rituximab + lenalidomide |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Eligible participants must meet all of the following criteria:
- Provide written informed consent. Age ≥18 years . Histologically confirmed relapsed/refractory follicular lymphoma (R/R FL) . Received at least two prior lines of systemic therapy , including anti-CD20 monoclonal antibody therapy.
- ECOG performance status 0-1 . Measurable disease , with longest diameter >1.5 cm . Estimated life expectancy (per investigator assessment) ≥18 weeks . Adverse events from prior anticancer therapy must have resolved to ≤ grade 1 (except alopecia and anorexia).
- Total bilirubin ≤1.5 × ULN ; for patients with documented Gilbert syndrome: total bilirubin ≤3 × ULN with predominantly indirect hyperbilirubinemia.
- AST and ALT ≤3 × ULN .
Key exclusion criteria (17 listed)
- Participants meeting any of the following will be excluded:
- Participants already enrolled who meet any of the following will be treated as excluded cases in statistical analyses:
- Post-enrollment discovery of non-fulfillment of eligibility criteria. Prior exposure to zanubrutinib or other BTK inhibitors. Intolerable toxicity after taking zanubrutinib or other BTK inhibitors. Received fewer than two consecutive administrations after enrollment such that objective efficacy cannot be assessed (adverse events may still be assessable).
- Protocol violations. Prior hematopoietic stem cell transplantation.
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 |
|---|---|---|
| tislelizumab + zanubrutinib + rituximab + lenalidomidePatients with FL will receive a PD-1 + ZR² regimen (tislelizumab + zanubrutinib + rituximab + lenalidomide) for 6 cycles (3 weeks per cycle). Induction Phase (Cycles 1-6; 21 days per cycle) Zanubrutinib (Z): 160 mg orally twice daily (BID). Rituximab (R): 375 mg administered intravenously on Day 1 of cycles 1-6; additionally administered on Day 1 of cycles 2-8/12 per protocol (21-day cycles). Lenalidomide: 20 mg orally once daily on cycles 1-6. Tislelizumab: 200 mg intravenous infusion on Day 1 every 3 weeks. After 6 cycles of the four-drug combination, response will be assessed by CT/PET-CT. Patients achieving CR/PR/SD will proceed to maintenance; those not achieving at least SD will discontinue the study. Maintenance Phase Patients achieving CR/PR/SD during induction will receive: Zanubrutinib: 160 mg orally BID; and Tislelizumab: 200 mg IV on Day 1 every 3 weeks until disease progression, unacceptable toxicity, or completion of 1 year of maintenance. | Drug | PD-1+ZR2 |
Primary outcome
Complete response rate (CRR)
Time frame: Within 21 days after the completion of the 6th cycle of induction therapy (Each cycle is 21 days)
The proportion of evaluable participants who achieve complete response (CR) following 6 cycles of induction therapy. CR is defined in accordance with the 2014 Lugano Classification for Lymphoma: this requires the complete disappearance of all measurable/evaluable lymphoma lesions, resolution of all disease-related clinical symptoms, and normalization of imaging findings (e.g., no residual measurable disease on CT/MRI, and no metabolically active disease on FDG-PET/CT). The analysis population is restricted to participants who complete at least 4 cycles of induction therapy and have available post-treatment efficacy assessment data.
4 secondary outcomes
Objective response rate (ORR)
Time frame: Within 21 days after the completion of the 6th cycle of induction therapy At the end of Cycle 1 (each cycle is 21 days)
2-Year Progression-Free Survival (PFS)
Time frame: Up to 2 years after Start treatment
2-Year Overall Survival (OS)
Time frame: Up to 2 years after start treatment
Incidence of Treatment-Related Adverse Events (TRAE)
Time frame: From the first dose of study intervention to 30 days after the last dose of study intervention
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 18 Feb 2026.
- Individual participant dataSharing planned: No
Related trials for Relapsed/Refractory Follicular Lymphoma
RecruitingPhase 1/2
A Platform Trial Evaluating New Drugs or Combination in R/R Peripheral T-cell Lymphomas
Peripheral T Cells Lymphoma (PTCL), Follicular Helper T-Cell Lymphoma
RecruitingPhase 1/2
Dose Escalation and Dose Expansion Study of MDX2003 in Patients With Different Types of Lymphoma
Lymphoma, Waldenström Macroglobulinemia (WM)
Active, not recruitingPhase 1/2
Trial of the Safety and Efficacy of Epcoritamab in Japanese Subjects With Relapsed or Refractory (R/R) B-Cell Non-Hodgkin Lymphoma (R/R B-NHL)
Diffuse Large B Cell Lymphoma, High-grade B-cell Lymphoma
Active, not recruitingPhase 1
Study to Evaluate Adverse Events, Change in Disease Activity, and How Oral ABBV-101 Moves Through the Body in Adult Participants With B-Cell Malignancies
Hematologic Cancer
Active, not recruitingPhase 1
Pembrolizumab and Vorinostat in Patients With Relapsed or Refractory DLBCL, FCL or HL.
Grade 3b Follicular Lymphoma, Recurrent B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between DLBCL and Classic HL
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.
Wei Xu, PhD contact
Wei Xu, PhD principal investigator
Hematological Department, Jiangsu Province Hospital
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 tislelizumab + zanubrutinib + rituximab + lenalidomide in people with Relapsed/Refractory Follicular Lymphoma, run by The First Affiliated Hospital with Nanjing Medical University 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 10 inclusion and 17 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 18 Feb 2026. 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 Jinhua Liang (15952032421, 1151525490@qq.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete response rate (CRR) (time frame: Within 21 days after the completion of the 6th cycle of induction therapy (Each cycle is 21 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 18 Feb 2026.