Combination of Zanubrutinib, Rituximab and Venetoclax in Patients With Previously Untreated Follicular Lymphoma (ZARAV)

July 16, 2026 updated by: Han weidong, Chinese PLA General Hospital

Safety and Efficacy of Zanubrutinib in Combination With Rituximab and Venetoclax in Previously Untreated Follicular Lymphoma: An Open Label, Phase 2 Study

This is a single center, open label, single arm phase II clinical trial. The objective of this study is to assess the feasibility and efficacy of zanubrutinib combined with venetoclax and Rituximab in patients with previously untreated follicular lymphoma (FL) .

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Follicular lymphoma (FL)is the most common inert non Hodgkin's lymphoma (iNHL). Their natural courses are slow but highly variable. The standard first-line treatment of advanced FL is based on rituximab. Whether combined with chemotherapy or not, it can induce lasting remission, but it is usually incurable. Although the first-line immunochemotherapy regimen has high efficacy, it also has high toxicity. Cytotoxic chemotherapy is related to many side effects, including bone marrow suppression and immunosuppression, gastrointestinal and cardiac toxicity, neurotoxicity and the occurrence of secondary tumors. About 20% of FL patients relapse within 2 years after first-line chemotherapy. The overall prognosis of these patients is poor. This clinical trial aims to evaluate the feasibility and efficacy of free-chemotherapy regimen (zanubrutinib combined with venetoclax and Rituximab) in patients with previously untreated follicular lymphoma.

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • Beijing, China, 100853
        • Recruiting
        • Biotherapeutic Department and Hematology Department of Chinese PLA General Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • A diagnosis of follicular lymphoma (grades 1, 2, or 3a), untreated.
  • Stage II, III, or IV disease.
  • Able and willing to provide written informed consent and to comply with the study protocol.
  • at least one measurable disease.

  • Must be in need of therapy as evidenced by at least one of the following criteria:

    • Presence of at least one B symptom: Fever (> 38 Celsius [C]) not due to infectious etiology, or Night sweats, or Weight loss > 10% in the past 6 months;
    • Fatigue due to lymphoma;
    • Splenomegaly (> 13 cm);
    • Compression syndrome (ureteral, orbital, gastrointestinal);
    • Any of the following cytopenias, due to lymphoma: Hemoglobin ≤ 10 g/dL, or Platelets ≤ 100 x 10^9/L, or Absolute neutrophil count (ANC) < 1.5 x 10^9/L;
    • Pleural or peritoneal effusion;
    • Lactate dehydrogenase (LDH) > upper limit of normal (ULN) or beta (B)2 microglobulin > ULN;
    • Other lymphoma-mediated symptoms as determined by the treating physician.
  • ECOG ≤ 2
  • ANC > 1.0 x 10^9/L (for patients without bone marrow involvement by lymphoma)
  • Platelet count > 50 x 10^9/L (for patients without bone marrow involvement by lymphoma)
  • Prothrombin time (PT)/international normal ratio (INR) < 1.5 x (upper limit of normal) ULN and partial thromboplastin time (PTT) (activated partial thromboplastin time [aPTT]) < 1.5 x ULN (unless abnormalities are unrelated to coagulopathy or bleeding disorder). When treated with warfarin or other vitamin K antagonists, then INR ≤ 3.0)
  • Serum aspartate transaminase (AST) and alanine transaminase (ALT) < 3 x ULN
  • Creatinine clearance > 30 ml/min calculated by modified Cockcroft-Gault formula
  • Bilirubin < 1.5 x ULN unless bilirubin is due to Gilbert's syndrome, documented liver involvement with lymphoma, or of non-hepatic origin, in which case bilirubin should not exceed 3 g/dL
  • Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [B-hCG]) pregnancy test at screening. Women who are pregnant or breastfeeding are ineligible for this study

Exclusion Criteria:

  • Known active central nervous system lymphoma or leptomeningeal disease
  • Follicular lymphoma with evidence of diffuse large B-cell transformation
  • Grade 3b follicular lymphoma
  • Any prior history of other malignancy besides follicular lymphoma
  • History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
  • Patients who have undergone major surgery within 14 days
  • The researchers believe that it is not advisable for the participant to take part in this trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (zanubrutinib, venetoclax, rituximab)

stage I (cycles 1-3, every 4 weeks): zanubrutinib PO 160mg, BID; rituximab IV on day 1.

stage II (cycles 4-9, every 4 weeks): if complete response : zanubrutinib PO 160mg, BID; rituximab IV on day 1.

if no complete response : zanubrutinib PO160mg, BID; rituximab IV on day 1 and Venetoclax PO (100mg D1, 200mg D2, and 400mg D3 of cycle 4; 400mg QD).
Drug: Venetoclax
BCL-2 inhibitor
Drug: Zanubrutinib
BTK inhibitor
Biological: Rituximab
Monoclonal antibody to CD20

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
CR rate
Time Frame: Within 6 months of therapy completion
Determined by PET/CT based on Cheson, Lugano classification 2014 as assessed by the investigator. The number and percentage of subjects with a CR will be tabulated.
Within 6 months of therapy completion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall response rate (ORR)
Time Frame: Within 6 months of therapy completion
CR + partial response (PR), determined by PET/CT based on Cheson, Lugano classification 2014 as assessed by the investigator. The number and percentage of subjects with an ORR will be tabulated.
Within 6 months of therapy completion
Progression-free survival
Time Frame: up to two years
PFS is defined as the duration from date of treatment initiation to date of disease progression or death from any cause
up to two years
Overall survival
Time Frame: up to two years
PFS is defined as the duration from date of treatment initiation to date of death from any cause
up to two years
Incidence of Treatment-Emergent Adverse Events
Time Frame: Up to 90 days after the last dose of study drugs
Incidence of subjects occuring treatment related adverse events.
Up to 90 days after the last dose of study drugs

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chinese PLA General Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 10, 2024

Primary Completion (Estimated)

December 30, 2026

Study Completion (Estimated)

June 1, 2027

Study Registration Dates

First Submitted

June 18, 2024

First Submitted That Met QC Criteria

June 18, 2024

First Posted (Actual)

June 24, 2024

Study Record Updates

Last Update Posted (Actual)

July 20, 2026

Last Update Submitted That Met QC Criteria

July 16, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHN-PLAGH-BT-086

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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