Zanubrutinib combined with R-CHOP for treating newly diagnosed DLBCL with p53 expression

Zanubrutinib Combined With Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in the Treatment of Newly Diagnosed Diffuse Large B-cell Lymphoma With p53 Protein Expression

This study is testing if a new combination of zanubrutinib and R-CHOP can help people with newly diagnosed diffuse large B-cell lymphoma who have high levels of p53 protein.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 41 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Huazhong University of Science and Technology (Academic / other)
• Drugs / interventions: zanubrutinib
• Locations: 1 site (Wuhan, Hubei)
• Trial ID: NCT06005870 on ClinicalTrials.gov

What this trial studies

This study evaluates the efficacy and safety of zanubrutinib in combination with R-CHOP for patients newly diagnosed with diffuse large B-cell lymphoma (DLBCL) who have p53 protein expression of 50% or more. It is a prospective, single-arm, single-center study that aims to recruit 41 patients. The study follows a two-phase design, where the first phase requires at least 12 patients to achieve a complete response to proceed to the second phase. Participants will receive 6 cycles of treatment, with interim assessments to evaluate their response after 4 cycles.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with newly diagnosed DLBCL and positive p53 expression.

Not a fit: Patients with previous systemic treatment for DLBCL or those with ECOG scores above 2 may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve outcomes for patients with DLBCL who express p53 protein, potentially leading to higher response rates and better survival.

How similar studies have performed: While there have been studies on DLBCL treatments, the specific combination of zanubrutinib with R-CHOP in this context is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Age ≥18 years, ≤ 75 years, both sexes;
2. Diff use large B-cell lymphoma diagnosed by histopathology without previous systemic DLBCL treatment;
3. ECOG score: 0-2;
4. Predicted survival ≥3 months;
5. Patients with positive p53 expression detected by immunohistochemistry (≥50% );
6. The patients had certain conditions of organ function reserve, and the laboratory tests within 1 week before enrollment met the following conditions:

Blood routine: neutrophil count (NEUT) ≥1.5×10\^9/L, platelet count (PLT)

≥75×10\^9/L, hemoglobin (HGB) ≥80 g/L; G-CSF was not used in the past 7 days (the researchers judged that the lymphoma-induced cytopenia could be included).

Liver function: Total bilirubin (TBIL) ≤1.5× upper limit of the normal range (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN; If liver metastases were present, TBIL≤3×ULN, ALT and AST≤5×ULN; Renal function: serum creatinine (Cr) ≤2.0×ULN or creatinine clearance (CCr) ≥60ml/min;

Cardiac function: LVEF≥50%, ECG did not indicate any acute myocardial infarction, arrhythmia, or atrioventricular conduction block above grade I;

Thyroid function: thyroid stimulating hormone (TSH) was within the normal range. If TSH is abnormal, free triiodothyronine (FT3) and free thyroxine (FT4) should be within the normal range or abnormal without clinical significance.

1. According to the Lugano2014 assessment criteria, patients must have measurable lesions, defined as the longest diameter of at least one nodule \> 1.5cm, or the longest diameter of at least one nodule \> 1cm, and at least two vertical diameters that can be accurately measured.
2. Patients volunteered to participate in the trial, understood the study procedure, and were able to sign in-person informed consent.

Exclusion Criteria:

1. Patients with definite lymphoma central nervous system (CNS) infiltration, including brain parenchyma, meningeal invasion, or spinal cord compression;
2. severe or uncontrolled infection;
3. with active autoimmune disease;
4. Other serious medical conditions, such as uncontrolled diabetes, gastric ulcers, other serious cardiopulmonary diseases, etc. (the decision was left to the investigator);
5. patients who received the live attenuated vaccine within 4 weeks before the first dose or planned to receive the live attenuated vaccine during the study;
6. The subject has previous or co -e xis ting other malignant tumors; Patients with basal cell carcinoma of the skin and uterine and neck carcinoma in situ who had been cured for more than 3 years, and patients with other malignant tumors who had been cured for more than 5 years were considered for inclusion.
7. HIV-positive patients with active hepatitis B ( HBV-DNA \> 100 copies/m L), positive HCV antibody, or abnormal HCV-RNA
8. Women who were pregnant or lactating, women who planned to become pregnant between the study period and 6 months after the last dose, or men whose partners planned to become pregnant, who were unwilling to use a medically approve defective contraceptive method (e.g., intrauterine device or condom ) during the trial;
9. were allergic to any of the drugs in the study protocol;
10. ineligible for inclusion as judged by the investigator ;

Where this trial is running

Wuhan, Hubei

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (Recruiting)

Study contacts

• Study coordinator: Liling Zhang, M.D

Conditions Diffuse Large B Cell Lymphoma; DLBCL; Diffuse Large b-cell lymphoma; p53; zanubrutinib