Elderly patients with untreated diffuse large B-cell lymphoma receiving a new treatment regimen

Prospective Single-arm, Single-center Clinical Study of Zanubrutinib, Polatuzumab Vedotin and Rituximab (ZPR) Regimen in Elderly Treatment-naive Patients With Diffuse Large B-cell Lymphoma

This study is testing a new combination of treatments for elderly patients with untreated diffuse large B-cell lymphoma to see how well it works and how safe it is.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 60 Years and up
• Sex: All
• Sponsor: Shanghai Zhongshan Hospital (Academic / other)
• Drugs / interventions: chemotherapy, prednisone, Polatuzumab, Rituximab, Zanubrutinib
• Locations: 1 site (Shanghai, Shanghai)
• Trial ID: NCT05940064 on ClinicalTrials.gov

What this trial studies

This clinical study investigates the efficacy and safety of a treatment regimen consisting of Zanubrutinib, Polatuzumab vedotin, and Rituximab in elderly patients who have not previously received treatment for diffuse large B-cell lymphoma (DLBCL). It is a prospective, single-arm, single-center study where participants will undergo six cycles of the ZPR regimen, followed by continued treatment with Zanubrutinib for up to one year or until disease progression. The primary objective is to evaluate the overall response rate (ORR) to this regimen, while secondary objectives focus on assessing the safety of the treatment.

Who should consider this trial

Good fit: Ideal candidates are elderly patients aged 60 and above with untreated diffuse large B-cell lymphoma and specific health criteria.

Not a fit: Patients with primary central nervous system lymphoma or those who have received any prior anti-DLBCL therapy will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for elderly patients with treatment-naive diffuse large B-cell lymphoma.

How similar studies have performed: While this approach is novel for this specific patient population, similar studies have shown promising results with the individual components of the ZPR regimen.

Eligibility criteria

Inclusion Criteria:

Patients must meet all of the following inclusion criteria to be enrolled in this study:

1. Patients with histopathologically confirmed DLBCL;
2. Patients haven't received any anti-DLBCL therapy. Corticosteroids alone is not considered as a line of treatment;
3. The age of patients ≥ 70 years old, or between 60 and 69 but with an ECOG score between 2-4;
4. Patients intolerant to standard front-line therapy, i.e. R-CHOP, or R-miniCHOP etc.
5. Good organ function;
6. Measurable lesions detected by radiological imaging were defined as the longest diameter of at least 1 lymph node lesion \> 1.5 cm, or the longest diameter of at least 1 extranodal lesion \> 1.0 cm, and at least 2 vertical diameters that could be accurately measured;
7. Life expectancy ≥ 6 months;
8. Sign written informed consent.

Exclusion Criteria:

Patients with any of the following conditions cannot be enrolled in this study:

1. Patients with primary central nervous system lymphoma;
2. Patients with previous exposure to BTK inhibitors;
3. Accompanied by uncontrolled cardiovascular and cerebrovascular diseases, coagulation disorders, connective tissue diseases, serious infectious diseases, etc; Currently clinically significant active cardiovascular disease, such as uncontrolled arrhythmia, congestive heart failure, any grade 3 or 4 heart disease defined by the New York Heart Association functional classification, or history of myocardial infarction within 6 months after screening. The left ventricular ejection fraction measured by echocardiography was \< 50%;
4. Abnormal laboratory indicators at screening (unless caused by lymphoma):

   4.1 ANC\<1.5×10\^9/l, PLT\<80×10\^9/l 4.2 Coagulation function: INR greater than 1.5 times the upper limit of normal value; Pt and APTT were greater than 1.5 times the upper limit of normal 4.3 Liver function: ALT or ast was 2 times higher than the upper limit of normal, AKP and bilirubin were 1.5 times higher than the upper limit of normal 4.4 Renal function: creatinine was 1.5 times higher than the upper limit of normal, creatinine clearance rate was \< 60 ml/min (estimated according to Cockcroft Gault formula)
5. HIV-infected persons;
6. HCV active infection;
7. HBsAg positive patients need to be HBV DNA negative before enrollment; In addition, if the patient is HBsAg negative but HBcAb positive (regardless of HBsAb status), HBV DNA testing is still required. If the result is positive, antiviral treatment is required, and HBV DNA is required to be negative before enrollment;
8. Other concurrent and uncontrolled medical conditions that the investigator believes will affect the patient's participation in the study, including psychiatric patients or other patients who are known or suspected to be unable to fully comply with the study protocol;
9. Known allergy to test drug;
10. Inability to swallow capsules or suffering from diseases that seriously affect gastrointestinal function, such as malabsorption syndrome, gastrectomy or small bowel resection, symptomatic inflammatory bowel disease, or partial or complete intestinal obstruction;
11. Pregnant or lactating women;
12. Corticosteroids (dose equivalent to prednisone \> 20 mg/ day) were previously given for antitumor purposes within 7 days, and chemotherapy, targeted therapy, or radiotherapy were previously received within 3 weeks, or antibody-based therapy was received within 3 weeks, or traditional Chinese medicine anticancer therapy was performed within 4 weeks;
13. Major surgery was performed within 4 weeks after screening;
14. Sustained treatment with potent and moderate CYP3A inhibitors or CYP3A inducers is needed. Patients could not be enrolled if they had taken potent and moderate CYP3A inhibitors or CYP3A inducers within 7 days before the first administration of study drugs (or had taken these drugs for no more than 5 half-lives).

Where this trial is running

Shanghai, Shanghai

• Zhongshan Hospital，Fudan University — Shanghai, Shanghai, China (Recruiting)

Study contacts

• Principal investigator: Peng Liu, Ph.D — Fudan University
• Study coordinator: Peng Liu, Ph.D

Conditions Diffuse Large B Cell Lymphoma; Treatment-naive; Elderly; Zanubrutinib; Polatuzumab Vedotin; Rituximab; Efficacy; Safety