RecruitingPhase 2NCT07418190

Efficacy and Safety of Zanubrutinib, Rituximab, and Lenalidomide (ZR²) in Combination With Tislelizumab for Relapsed/Refractory Follicular Lymphoma


Sponsor

The First Affiliated Hospital with Nanjing Medical University

Enrollment

33 participants

Start Date

Feb 1, 2026

Study Type

INTERVENTIONAL

Conditions

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 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.


Eligibility

Min Age: 18 YearsMax Age: 75 Years

Plain Language Summary

Simplified for easier understanding

This study tests a four-drug combination — zanubrutinib (BTK inhibitor), rituximab, lenalidomide, and tislelizumab (a checkpoint immunotherapy) — for people with follicular lymphoma (a slow-growing blood cancer) that has returned or stopped responding to previous treatments. **You may be eligible if...** - You are 18 or older - You have follicular lymphoma confirmed by biopsy that has relapsed or is refractory - You have received at least two prior lines of therapy, including an anti-CD20 drug - You have signed informed consent **You may NOT be eligible if...** - Your lymphoma has not been previously treated - You have certain serious organ problems or other active cancers - You have not had prior systemic therapy Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DRUGtislelizumab + zanubrutinib + rituximab + lenalidomide

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.


Locations(1)

Jiangsu Province Hospital

Nanjing, Jiangsu, China

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NCT07418190


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