Combining zanubrutinib with rituximab and chemotherapy for newly diagnosed PCNSL patients who can't tolerate HSCT

Zanubrutinib Combined With Rituximab and Chemotherapy for Newly-Diagnosed Primary Central Nervous System Large B-Cell Lymphoma Patients Intolerant to Haematopoietic Stem Cell Transplantation

This study is testing a new treatment combining zanubrutinib, rituximab, and chemotherapy for people newly diagnosed with a type of brain lymphoma who can't handle a specific stem cell transplant.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 29 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Ruijin Hospital (Academic / other)
• Drugs / interventions: rituximab, zanubrutinib, methotrexate
• Locations: 1 site (Shanghai, Shanghai)
• Trial ID: NCT05896007 on ClinicalTrials.gov

What this trial studies

This open-label, single-arm study evaluates the effectiveness and tolerability of zanubrutinib when combined with rituximab and either methotrexate or temozolomide in patients newly diagnosed with primary central nervous system large B-cell lymphoma who are intolerant to hematopoietic stem cell transplantation. Participants will undergo six cycles of this new treatment regimen, and those who achieve complete or partial responses will continue with zanubrutinib maintenance therapy for one year, provided they can tolerate it. The study aims to provide a new therapeutic option for this challenging patient population.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 80 with histopathologically confirmed CD20 positive primary large B-cell lymphoma of the CNS or primary vitreoretinal lymphoma.

Not a fit: Patients who are pregnant or have severe comorbidities that prevent participation may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new effective option for patients with PCNSL who cannot undergo HSCT.

How similar studies have performed: While similar approaches have been explored, this specific combination of zanubrutinib with rituximab and chemotherapy in this patient population is novel.

Eligibility criteria

Inclusion Criteria:

* 18 to 80 years old;
* Histopathologically confirmed CD20 positive primary large B-cell lymphoma of the central nervous system (CNS) or primary vitreoretinal lymphoma according to the 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours \[primary large B-cell lymphoma of the CNS previously named as primary diffuse large B-cell lymphoma (DLBCL) of the CNS in the revised 4th edition\];
* Life expectancy of \> 3 months (in the opinion of the investigator);
* Creatinine Clearance Rate (CCR) ≥ 50 mL/min or estimated Glomerular Filtration Rate (eGFR) ≥ 60 mL/(min·1.73 m\^2);
* International Normalized Ratio (INR) ≤ 1.5 and activated Partial Thromboplastin Time (aPTT) ≤ 1.5 times the upper limit of normal;
* Left Ventricular Ejection Fraction (LVEF) ≥ 50%;
* Agreeing to provide written informed consent prior to any special examination or procedure for the research on their own or legal representative.

Exclusion Criteria:

* Pregnant or lactating women;
* Known Hepatitis B Virus (HBV) and/or Hepatitis C Virus (HCV) infection (HBV infection refers to HBV-DNA \> detectable limit);
* With acquired or congenital immunodeficiency;
* With congestive heart failure in 6 months before enrollment, New York Heart Association (NYHA) heart function class III or IV, or LVEF \< 50%;
* Known to be allergic to the test drug ingredients;
* Diagnosed with or being treated for malignancy other than lymphoma;
* With severe infection;
* Substance abuse, medical, psychological, or social conditions that may interfere with the subjects' participation in the study or evaluation of the study results;
* Deemed unsuitable for the group.

Where this trial is running

Shanghai, Shanghai

• Ruijin Hospital — Shanghai, Shanghai, China (Recruiting)

Study contacts

• Study coordinator: Weili Zhao, Doctor

Conditions PCNSL; zanubrutinib