This phase II clinical trial is designed to evaluate a novel combination treatment for patients with newly diagnosed central nervous system lymphoma (CNSL) who are not candidates for stem cell transplantation. The study will assess the safety and effectiveness of combining selinexor (an oral selective nuclear export inhibitor) with high-dose methotrexate and rituximab chemotherapy, followed by low-dose whole-brain radiotherapy (WBRT). Selinexor has shown promise in enhancing the effects of chemotherapy and radiation in blood cancers.
Patients enrolled in this open-label, single-arm, multicenter study will receive up to six 21-day treatment cycles. Those who respond well will undergo reduced-dose WBRT and continue selinexor as maintenance therapy. The study will measure how many patients respond to the treatment (overall response rate), how long the response lasts (progression-free survival), overall survival, and safety.
This research aims to provide a less toxic and more effective option for treating CNSL in patients who are older or medically unfit for transplantation.
Age ≥ 18 years, male or female.
Histologically confirmed primary CNS lymphoma (PCNSL) or secondary CNS lymphoma (SCNSL) with CNS-only involvement.
Ineligible for autologous stem cell transplantation based on clinical assessment or patient refusal.
At least one measurable brain lesion ≥1 cm in diameter, or positive cerebrospinal fluid (CSF) cytology/flow cytometry for patients with leptomeningeal disease.
CNS involvement limited to intraocular lymphoma only.
Prior systemic therapy for CNS lymphoma.
SCNSL with active systemic (non-CNS) disease involvement.
Uncontrolled intracranial hypertension.
Single group
Selinexor + High-dose Methotrexate + Rituximab + WBRT
DrugRituximab 375 mg/m² intravenously on Day 0 of each 21-day cycle High-dose Methotrexate (HD-MTX) 3.5 g/m² intravenously over 4 hours on Day 1 of each cycle Selinexor 80 mg orally once weekly (on Days 1, 8, and 15) during each cycle Treatment is administered every 21 days for up to 6 cycles. Tumor response will be evaluated every 3 cycles. Patients who achieve a partial response (PR) or better will undergo consolidative low-dose whole-brain radiotherapy (WBRT) at 23.4 Gy in 13 fractions.
ORR
The proportion of participants who achieve a complete response (CR) or partial response (PR) as assessed by investigators according to the 2014 Lugano classification for lymphoma response evaluation.
PFS
Time from enrollment to disease progression or death from any cause, whichever occurs first.
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