Zanubrutinib plus Pola-R-CHP for newly diagnosed high-risk diffuse large B‑cell lymphoma

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

This tests whether adding the BTK inhibitor zanubrutinib to a Pola-R-CHP regimen helps people with newly diagnosed DLBCL who have high-risk features.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Beijing Tongren Hospital (Academic / other)
• Drugs / interventions: polatuzumab, rituximab, zanubrutinib
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT07371923 on ClinicalTrials.gov

What this trial studies

This single-center, phase 2 trial gives treatment‑naive patients with measurable DLBCL and prespecified high‑risk features a combination regimen including zanubrutinib and Pola-R-CHP, with alternative backbone adjustments (for example rituximab plus high‑dose methotrexate) for certain CNS presentations. Eligible patients have at least one high‑risk factor such as IPI ≥2, ABC subtype, double‑expressor or double‑hit biology, CD5 positivity, MCD/N1/A53 subtypes, or multiple extranodal/special-site involvement. The study measures safety and anti‑lymphoma activity, focusing on response rates and progression‑free survival compared to historical outcomes with R‑CHOP. Treatment is administered and patients are followed at Beijing Tongren Hospital.

Who should consider this trial

Good fit: Adults with newly diagnosed, measurable DLBCL who have at least one listed high‑risk feature, ECOG 0–3, adequate blood and organ function, expected survival ≥3 months, and no prior lymphoma therapy are ideal candidates.

Not a fit: Patients without high‑risk features, those with other active malignancies, prior lymphoma treatment (beyond short corticosteroids), or inadequate organ function are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the regimen could increase remission and progression‑free survival rates for patients with newly diagnosed high‑risk DLBCL and potentially reduce CNS relapses.

How similar studies have performed: Polatuzumab added to frontline regimens has shown improved 2‑year PFS in prior trials, while combining BTK inhibitors like zanubrutinib with frontline chemoimmunotherapy remains investigational with promising but unproven results.

Eligibility criteria

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.

Where this trial is running

Beijing, Beijing Municipality

• Beijing Tongren Hospital — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Study coordinator: Liang Wang, M.D.

Conditions Diffuse Large B Cell Lymphoma; diffuse large b cell lymphoma; BTK inhibitors; zanubrutinib; high-risk factors