Zanubrutinib, Obinutuzumab Combined With Lenalidomide (ZGR) for the Treatment of Untreated Follicular Lymphoma

NCT07299149 | Recruiting Phase 2

• 1 other identifier: IIT2025107
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Follicular Lymphoma

Keywords

follicular lymphoma; zanubrutinib; Obinutuzumab; lenalidomide

Outcome Measures

Primary Outcomes (1)

• Objective response rate，ORR

  Defined as the proportion of patients with complete or partial response as assessed by response to induction therapy

  up to the end of 6 cycles of treatment(each cycle is 28 days)]

Secondary Outcomes (9)

• Complete response rate，CRR

  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

  Up to the end of 6 cycles of treatment(each cycle is 28 days)

• CRR and ORR at end of treatment

  at the end of Cycle 24 (each cycle is 28 days)

• Progression-free survival (PFS)

  up to 5 years

• Duration of response (DOR)

  up to 5 years

Other Outcomes (2)

• Minimal residual disease (MRD) monitoring

  Up to the end of 24 cycles of treatment(each cycle is 28 days)

• Circulating tumor DNA (ctDNA) analysis via next-generation sequencing (NGS)

  Up to the end of 24 cycles of treatment(each cycle is 28 days)

Study Arms (1)

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)

Drug: Induction Therapy: Zanubrutinib, obinutuzumab, lenalidomide; Drug: Maintenance therapy: Zanubrutinib, lenalidomide

Interventions

Induction Therapy: Zanubrutinib, obinutuzumab, lenalidomide DRUG

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.

Experimental: Induction therapy of ZGR, and maintenance therapy of ZR

Maintenance therapy: Zanubrutinib, lenalidomide DRUG

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

Experimental: Induction therapy of ZGR, and maintenance therapy of ZR

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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)

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (2)

Institute of Hematology and Blood Diseases Hospital ,Chinese Academy of Medical Sciences, Tianjin, Tianjin 300020

Tianjin, Tianjin Municipality, 300020, China

NOT YET RECRUITING

Institute of Hematology and Blood Diseases Hospital ,Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, 300020, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

obinutuzumab; Lenalidomide

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Shuhua Yi

  Institute of Hematology & Blood Diseases Hospital, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shuhua Yi, Dr

CONTACT

+86-022-23909106; yishuhua@ihcams.ac.cn

Rui Lyu

CONTACT

+86-022-23909106; lvrui@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2025
• First Posted: December 23, 2025
• Study Start: December 25, 2025
• Primary Completion (Estimated): April 28, 2028
• Study Completion (Estimated): December 25, 2030
• Last Updated: May 13, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)