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

NCT07371923 | Recruiting Phase 2

• 1 other identifier: TRhos-DLBCL-01
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Diffuse Large B Cell Lymphoma (DLBCL)

Keywords

diffuse large b cell lymphoma (DLBCL); BTK inhibitors; zanubrutinib; high-risk factors

Outcome Measures

Primary Outcomes (1)

• Best complete remission rate (CRR)

  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 Outcomes (3)

• best overall response rate (ORR)

  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

  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

  From the start of the first cycle of treatment up to 24 months after initiation of treatment for the last enrolled patient.

Study Arms (1)

treatment arm (for DLBCL patients witout central nervous system lesions)

EXPERIMENTAL

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

Interventions

Zanubrutinib+Pola-R-CHP DRUG

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.

treatment arm (for DLBCL patients witout central nervous system lesions)

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beijing Tongren Hospital: lead

Study Sites (1)

Beijing Tongren Hospital

Beijing, Beijing Municipality, 100730, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Liang Wang, M.D.

CONTACT

+861058266633; wangliangtrhos@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of department of hematology, Beijing Tongren Hospital

Study Record Dates

• First Submitted: November 18, 2025
• First Posted: January 28, 2026
• Study Start: November 20, 2025
• Primary Completion (Estimated): February 29, 2028
• Study Completion (Estimated): August 31, 2028
• Last Updated: January 28, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)