ZGR: zanubrutinib plus obinutuzumab and lenalidomide for newly diagnosed splenic B‑cell lymphoma with prominent nucleoli

Zanubrutinib, Obinutuzumab, and Lenalidomide (ZGR) in the Treatment of Newly Diagnosed Splenic B-cell Lymphoma With Prominent Nucleoli (SBLPN): A Prospective, Open-label, Single-arm Clinical Trial

This trial tries the ZGR combination (zanubrutinib, obinutuzumab, and lenalidomide) as first‑line treatment for people with newly diagnosed SBLPN to see if it is effective and well tolerated.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 47 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (other)
• Drugs / interventions: prednisone, Obinutuzumab, Zanubrutinib, rituximab
• Locations: 1 site (Tianjin, Tianjin Municipality)
• Trial ID: NCT07165769 on ClinicalTrials.gov

What this trial studies

There is no established optimal first‑line therapy for splenic B‑cell lymphoma with prominent nucleoli (SBLPN), and existing regimens can cause significant toxicity or resistance. This single‑arm phase 2 trial gives untreated patients six cycles of induction therapy with zanubrutinib, obinutuzumab, and lenalidomide (ZGR), followed by maintenance zanubrutinib plus lenalidomide. The study measures preliminary efficacy outcomes and monitors safety and tolerability throughout treatment. The design aims to determine whether the targeted BTK inhibition plus enhanced anti‑CD20 antibody activity and immunomodulation can improve responses and survival with acceptable side effects in this rare disease.

Who should consider this trial

Good fit: Adults aged 18–80 with histologically or cytologically confirmed, previously untreated SBLPN who require therapy and meet the specified performance status and laboratory criteria are eligible.

Not a fit: Patients with prior systemic therapy for SBLPN, active central nervous system disorders, or those who do not meet the lab or performance requirements are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the ZGR regimen could provide a more effective and better‑tolerated first‑line treatment that improves response rates and survival for patients with SBLPN.

How similar studies have performed: BTK inhibitors combined with anti‑CD20 antibodies have shown benefit in other B‑cell lymphomas, but this exact combination of zanubrutinib, obinutuzumab, and lenalidomide in SBLPN is novel and not yet broadly tested.

Eligibility criteria

Inclusion Criteria:

* Aged 18 to 80 years, male or female
* Histologically or cytologically confirmed SBLPN requiring active treatment;
* No prior systemic therapy for SBLPN received;
* ECOG performance status of 0-2;
* Anticipated life expectancy ≥6 months;
* Laboratory parameters (hematologic and biochemical) meeting the following criteria:
* a. Absolute neutrophil count (ANC) ≥1.0 × 10⁹/L, platelet count ≥50 × 10⁹/L;
* b. Total bilirubin (TBIL) ≤2.0 × upper limit of normal (ULN);
* c. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN;
* d. Creatinine clearance ≥50 mL/min (calculated via Cockcroft-Gault formula or direct measurement).
* Men and women of childbearing potential must agree to use medically approved contraception throughout the study and for 4 weeks after treatment discontinuation;
* Participants must voluntarily enroll in the study and provide written informed consent.

Exclusion Criteria:

* History of central nervous system (CNS) disorders (including CNS lymphoma) diagnosed within 1 year prior to enrollment.
* Other primary malignancies within the past 3 years (excluding non-melanoma skin cancer, curatively treated localized prostate cancer, cervical carcinoma in situ, or squamous intraepithelial lesions on PAP smear).
* Exposure to any investigational drugs, antimicrobial agents, or participation in other interventional clinical trials within 4 weeks prior to enrollment.
* Major surgery (excluding lymph node biopsy) within 14 days before enrollment or anticipated requirement for major surgery during the study.
* Prior use of investigational agents targeting SBLPN.
* Active immunodeficiency, autoimmune diseases, prolonged systemic corticosteroid therapy (\>10 mg/day prednisone equivalent) within 7 days prior to enrollment, or any immunosuppressive therapy.
* Severe hepatic dysfunction (e.g., severe jaundice, hepatic encephalopathy, refractory ascites, hepatorenal syndrome), cachexia, multiorgan failure, or severe renal impairment.
* Clinically significant cardiovascular comorbidities:

New York Heart Association (NYHA) class III/IV heart failure; Myocardial infarction within 6 months prior to enrollment; Uncontrolled arrhythmias (including QTc interval ≥480 ms); Poorly controlled hypertension (systolic ≥150 mmHg/diastolic ≥100 mmHg despite antihypertensives); Unstable angina.

* Bleeding diathesis or coagulation disorders; thrombotic events within 3 months prior to enrollment.
* Hypersensitivity to active ingredients or excipients of the investigational drugs.
* Pregnancy, lactation, or women of childbearing potential unwilling/unable to use contraception.
* Other conditions deemed unsuitable for participation by the investigator (e.g., compromised protocol compliance or safety risks).

Where this trial is running

Tianjin, Tianjin Municipality

• Institute of Hematology and Blood Diseases Hospital ,Chinese Academy of Medical Sciences — Tianjin, Tianjin Municipality, China (RECRUITING)

Study contacts

• Principal investigator: Shuhua Yi, Dr — Institute of Hematology & Blood Diseases Hospital, China
• Study coordinator: Shuhua Yi, Dr

Conditions: Splenic B-cell Lymphoma/Leukaemia With Prominent Nucleoli，SBLPN