Combining orelabrutinib with rituximab and chemotherapy for treating relapsed B-cell lymphoma in the brain

Orelabrutinib Combined With Rituximab and Chemotherapy for Relapsed/Refractory B-Cell Lymphoma Patients With Central Nervous System Involvement

This study is testing a new combination of medicines, including orelabrutinib, rituximab, and chemotherapy, to see if it helps people aged 14 to 80 with relapsed B-cell lymphoma in the brain feel better.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 14 Years to 80 Years
• Sex: All
• Sponsor: Ruijin Hospital (Academic / other)
• Drugs / interventions: rituximab, orelabrutinib, chemotherapy
• Locations: 1 site (Shanghai, Shanghai)
• Trial ID: NCT05926427 on ClinicalTrials.gov

What this trial studies

This open-label, single-arm Phase 2 study evaluates the effectiveness and safety of orelabrutinib when combined with rituximab and chemotherapy in patients suffering from relapsed or refractory B-cell lymphoma that has spread to the central nervous system. Participants aged 14 to 80 will receive this combination therapy for six cycles, after which those achieving complete or partial remission may undergo autologous hematopoietic stem cell transplantation, with the option of continuing orelabrutinib maintenance therapy. The study aims to determine the potential benefits of this novel treatment approach in a challenging patient population.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 14 to 80 with confirmed CD20 positive B-cell lymphoma and CNS involvement who have previously undergone systemic treatment.

Not a fit: Patients with significant non-hematologic adverse events or those with severe hepatic or renal impairment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve outcomes for patients with difficult-to-treat CNS lymphoma.

How similar studies have performed: While there have been studies exploring similar combinations, this specific approach with orelabrutinib is relatively novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

* 14 to 80 years old;
* Histopathologically confirmed CD20 positive B-cell lymphoma according to the 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours;
* After systemic treatment of the CNS lesions;
* Life expectancy of \> 3 months (in the opinion of the investigator);
* No non-haematologic adverse events, except alopecia, higher than grade 1 according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0;
* Absolute Neutrophil Count (ANC) ≥ 1.0×10\^9/L, Platelet Count ≥ 50×10\^9/L and Haemoglobin ≥ 60 g/L, without transfusion or any use of pharmacologically hematopoietic drugs in 2 weeks;
* Serum Creatinine (SCr) ≤ 1.5 times the Upper Limit of Normal (ULN) or Creatinine Clearance Rate (CCR) ≥ 30 mL/min;
* Serum total Bilirubin (tBil) ≤ 1.5 × ULN and both Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 × ULN without hepatic metastases, otherwise tBil ≤ 3 × ULN and AST, ALT ≤ 5 × ULN respectively;
* International Normalized Ratio (INR) ≤ 1.5 and activated Partial Thromboplastin Time (aPTT) ≤ 1.5 × ULN;
* 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 Jiao Tong University School of Medicine — Shanghai, Shanghai, China (Recruiting)

Study contacts

• Study coordinator: Weili Zhao, Doctor

Conditions CNS Lymphoma; Relapse; Refractory; orelabrutinib