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 (ZGR in SBLPN)

Institute of Hematology & Blood Diseases Hospital, China

Status and phase: Enrolling; Phase 2

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

Treatments: Drug: Maintenance Therapy; Drug: Induction Therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT07165769

IIT2025004

Details and patient eligibility

About

:The aim of this study was to analyze the safety and efficacy of Zanubrutinib, Obinutuzumab, and Lenalidomide (ZGR) in the Treatment of Newly Diagnosed Splenic B-cell Lymphoma with Prominent Nucleoli (SBLPN).

The main questions it aims to explore the Preliminary Efficacy of the Zanubrutinib, Obinutuzumab, and Lenalidomide (ZGR) Regimen in the Treatment of Newly Diagnosed SBLPN Patients.

To explore the safety of zanubrutinib, obinutuzumab combined with lenalidomide (ZGR) in the treatment of newly diagnosed SBLPN patients.

Full description

There is no consensus on optimal first-line therapy for splenic B-cell lymphoproliferative neoplasms (SBLPN). Existing regimens like cladribine/bendamustine plus rituximab face toxicity and resistance. Targeting Bruton's tyrosine kinase (BTK), the novel BTK inhibitor zanubrutinib (highly selective, low toxicity) combined with obinutuzumab (enhanced antibody-dependent cytotoxicity) and lenalidomide (immunomodulation) shows promise. This single-arm trial evaluates the ZGR regimen (zanubrutinib, obinutuzumab, lenalidomide) for untreated SBLPN, including 6-cycle induction and maintenance therapy (zanubrutinib-lenalidomide), aiming to enhance efficacy, survival, and tolerability, offering a novel approach for this rare disease.

Enrollment: 47 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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47 participants in 1 patient group

Induction therapy and maintenance therapy of BGR

Experimental group

Description:

1. Induction Therapy Induction Therapy consists of zanubrutinib plus lenalidomide: each cycle lasts 28 days, up to 6 cycles, followed by maintenance therapy. 2. Maintenance Therapy Maintenance therapy consists of zanubrutinib plus lenalidomide: Lenalidomide is continued for 1 year. Zanubrutinib is continued for 2 years.

Treatment:

Drug: Induction Therapy

Drug: Maintenance Therapy