eligibility_summary
Inclusion: Adults 18–75, consented, relapsed/refractory PCNSL or SCNSL from DLBCL, MRI/CT progression or positive CSF (leptomeningeal only), response/stable ≥2 months to prior MTX-based therapy, prior auto-HSCT allowed, ECOG 0–3, adequate marrow/organ function, CrCl≥50, life expectancy >3 mo. Exclusion: active extra‑CNS therapy, intraocular-only, T‑cell PCNSL, relapse <6 mo post-MTX, only prior stereotactic RT, recent therapy, major cardiac disease/LVEF<50, infection, active HBV/HCV/HIV, GI issues, prior SINE, serious conditions.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Trial: single-arm phase 1/2 dose-escalation/expansion in relapsed/refractory primary or secondary CNS lymphoma. Interventions and mechanisms: 1) Selinexor (ATG-010) – oral small-molecule Selective Inhibitor of Nuclear Export (SINE) that blocks XPO1/CRM1, causing nuclear retention/reactivation of tumor suppressors (e.g., p53, RB, FOXO) and reduced oncoprotein expression, leading to apoptosis. 2) Methotrexate – high-dose antimetabolite (antifolate) chemotherapeutic inhibiting DHFR and thymidylate/purine synthesis, cytotoxic to rapidly dividing cells with CNS penetration. 3) Rituximab – chimeric anti-CD20 monoclonal antibody depleting B cells via CDC, ADCC, and apoptosis. Targets/pathways: CD20+ malignant B cells in CNS lymphoma, XPO1-mediated nuclear export pathway, folate/DHFR-dependent DNA synthesis pathway, immune effector mechanisms for B-cell clearance.