Application of Zanubrutinib-based Combination Regimens in the Treatment of Newly-diagnosed Diffuse Large B-cell Lymphoma

January 19, 2026 updated by: LIANG WANG, Beijing Tongren Hospital

Application of Zanubrutinib-based Combination Regimens in the Treatment of Newly-diagnosed Diffuse Large B-cell Lymphoma: A Phase II, Prospective, Single-center, Single-arm Clinical Study

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma. Currently, the first-line treatment regimen based on R-CHOP can only achieve clinical cure for 50% to 60% of patients. Previous studies have shown that patients with high-risk factors have a poor response to R-CHOP treatment and need further improvement. These high-risk factors include: IPI score ≥2 points, ABC subtype, double-expressing lymphoma, double-hit lymphoma, CD5-positive DLBCL, MCD subtype, N1 subtype, A53 subtype, extranodal lesions ≥2, special site involvement, such as central nervous system CNS, breast, testis, ovary, uterus, bone marrow, vitreoretinal, paraspinal, paranasal sinuses and intravascular, etc. Patients with DLBCL accompanied by high-risk factors also have a significantly increased risk of secondary CNS infiltration during recurrence. In previous RCHOP+X research strategies, only the combination of polatuzumab achieved significant 2-year PFS benefits in the overall population. None of the other studies achieved significant PFS benefits in the overall population. Therefore, the latest version of the CSCO guidelines recommends the Pola-R-CHP regimen as the first-line treatment for primary DLBCL. However, there is still considerable room for improvement in the survival of DLBCL patients with high-risk factors in clinical practice. Therefore, the strategy of the Pola-R-CHP-based combined with X regimen in high-risk DLBCL patients with specific risk factors can be explored subsequently.

The Phoenix study for young double expression of lymphoma patients, R - CHOP combined with BTK inhibitors can significantly improve the patient's survival, the subsequent omics data analysis indicates that MCD subtype, N1 subtypes and BN2 subtype can significantly benefit from BTK inhibitors. In addition, given that the proportion of MCD subtypes is high in most extranodal DLBCL patients and secondary CNS involvement is prone to occur, BTK inhibitors can effectively penetrate the blood-brain barrier (BBB) and have both preventive and therapeutic effects on CNS lesions. Therefore, exploring the application of BTK inhibitor zanubrutinib combined with R-CHOP or Pola-R-CHP regimens in high-risk DLBCL patients with specific risk factors (or zanubrutinib combined with rituximab and high-dose MTX in primary central nervous system DLBCL) has good application prospects. It is conducive to further improving the prognosis of such high-risk patients. Therefore, this study aimed to explore the efficacy and safety of the BTK inhibitor zanubrutinib combined with Pola-R-CHP regimen (or zanubrutinib combined with rituximab and high-dose MTX in primary central nervous system DLBCL, etc.) in patients of DLBCL with specific risk factors (IPI score two points or more, ABC subtypes, double expressor lymphoma, double hit lymphoma, CD5 positive DLBCL, MCD subtypes, N1 subtypes, A53 subtypes, extranodal lesions of 2 or more, special locations involved, such as the central nervous system (CNS, breast, testes).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This study aimed to explore the efficacy and safety of the BTK inhibitor zanubrutinib combined with Pola-R-CHP regimen (or zanubrutinib combined with rituximab and high-dose MTX in primary central nervous system DLBCL, etc.) in patients of DLBCL with specific risk factors (IPI score two points or more, ABC subtypes, double expressor lymphoma, double hit lymphoma, CD5 positive DLBCL, MCD subtypes, N1 subtypes, A53 subtypes, extranodal lesions of 2 or more, special locations involved, such as the central nervous system (CNS, breast, testes).

Study Type

Interventional

Enrollment (Estimated)

50

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

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:

  • Pathologically confirmed diffuse large B-cell lymphoma (DLBCL);
  • Have a "measurable lesions" ;
  • Have at least one of the following risk factors, including: IPI score ≥2 points, ABC subtype, double-expressor lymphoma, double-hit lymphoma, CD5-positive DLBCL, MCD subtype, N1 subtype, A53 subtype, extranodal lesions ≥2, special site involvement, such as central nervous system CNS, breast, testis, ovary, uterus, bone marrow, vitreoretinal, paraspinal, paranasal sinuses and intravascular, etc.
  • ECOG score 0-3;
  • Expected survival time for 3 months or more;
  • White blood cell count ≥3 x 10e9/L, the platelet count≥50 x 10e9/L; 1.5 mg/dL or less of serum creatinine, creatinine clearance≥50 ml/min; ALT, AST 3 x ULN or less, total bilirubin 2 x ULN or less.

Exclusion Criteria (the subject should not have any one of the following):

  • currently suffering from other malignant tumor;
  • ever received any treatments for lymphoma, except for short-term use of corticosteroids;
  • Allergic to any kind of study drug;
  • Active infection or uncontrol of HBV infection, HIV/AIDS or other serious infectious diseases;
  • Pregnancy and lactation women of childbearing age and are reluctant to take contraception subjects;
  • Researchers think that the subject does not fit to participate in this study.

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 arm (for DLBCL patients witout central nervous system lesions)
zanubrutinib combined with Pola-R-CHP regimen: zanubrutinib 160mg bid d1-d21/C1-C6; polatuzumab 1.8mg/kg d1/C1-C6; rituximab 375mg/㎡, iv, d1/C1-C6; cyclophosphamide 750mg/㎡, iv, d1/C1-C6; doxorubicin 50mg/㎡, iv, d1/C1-C6; predinisone 60mg/㎡ d1-5/C1-C6.
Drug: Zanubrutinib+Pola-R-CHP
zanubrutinib combined with Pola-R-CHP regimen: zanubrutinib 160mg bid d1-d21/C1-C6; polatuzumab 1.8mg/kg d1/C1-C6; rituximab 375mg/㎡, iv, d1/C1-C6; cyclophosphamide 750mg/㎡, iv, d1/C1-C6; doxorubicin 50mg/㎡, iv, d1/C1-C6; predinisone 60mg/㎡ d1-5/C1-C6.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Best complete remission rate (CRR)
Time Frame: From the start of the first cycle of treatment up to 24 weeks (when all six cycles of treatment was completed)
Response assessment was done after every two cycles of treatment. Best CRR was defined as the CRR during all the six cycles of treatment.
From the start of the first cycle of treatment up to 24 weeks (when all six cycles of treatment was completed)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
best overall response rate (ORR)
Time Frame: From the start of the first cycle of treatment up to 24 weeks (when all six cycles of treatment was completed).
Response assessment was done after every two cycles of treatment. Best ORR was defined as the ORR during all the six cycles of treatment.
From the start of the first cycle of treatment up to 24 weeks (when all six cycles of treatment was completed).
Two-year progression free survival (PFS) rate
Time Frame: From the start of the first cycle of treatment up to 24 months after initiation of treatment for the last enrolled patient.
PFS was caculated from the date of start of treatment to date of disease progression, death of any cause, or last follow-up, whichever came first.
From the start of the first cycle of treatment up to 24 months after initiation of treatment for the last enrolled patient.
Two-year overall survival (OS) rate
Time Frame: From the start of the first cycle of treatment up to 24 months after initiation of treatment for the last enrolled patient.
OS was caculated from the date of start of treatment to date of death of any cause, or last follow-up, whichever came first.
From the start of the first cycle of treatment up to 24 months after initiation of treatment for the last enrolled patient.

Collaborators and Investigators

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

Sponsor

Beijing Tongren 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)

November 20, 2025

Primary Completion (Estimated)

February 29, 2028

Study Completion (Estimated)

August 31, 2028

Study Registration Dates

First Submitted

November 18, 2025

First Submitted That Met QC Criteria

January 19, 2026

First Posted (Actual)

January 28, 2026

Study Record Updates

Last Update Posted (Actual)

January 28, 2026

Last Update Submitted That Met QC Criteria

January 19, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TRhos-DLBCL-01

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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