NCT07002099

Selinexor, High-dose Methotrexate, and Rituximab Combined With Radiotherapy for Newly Diagnosed, Transplant-ineligible Patients With Central Nervous System Lymphoma: An Open-label, Single-arm, Multicenter Phase II Study

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 26 (estimated)
• Sponsor: Second Affiliated Hospital of Soochow University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

This is a prospective, investigator-initiated, open-label, single-arm, multicenter phase II clinical trial designed to evaluate the efficacy and safety of a combination regimen consisting of selinexor, high-dose methotrexate (HD-MTX), and rituximab, followed by low-dose whole-brain radiotherapy (WBRT), in patients with newly diagnosed primary or secondary central nervous system lymphoma (PCNSL or SCNSL) who are not eligible for autologous stem cell transplantation (ASCT). Selinexor is a first-in-class, selective inhibitor of nuclear export (SINE) targeting XPO1/CRM1. By blocking nuclear export, selinexor restores nuclear localization and activity of multiple tumor suppressor proteins and growth regulatory factors. Preclinical studies suggest that selinexor may enhance the antitumor activity of chemotherapy and radiotherapy, particularly in hematologic malignancies. Its role in CNSL is supported by its ability to cross the blood-brain barrier and sensitize lymphoma cells to treatment. Eligible patients will receive six 21-day cycles of combination therapy: rituximab 375 mg/m² IV on day 0, HD-MTX 3.5 g/m² IV over 4 hours on day 1, and selinexor 80 mg orally once weekly (days 1, 8, and 15). Tumor response will be assessed every three cycles. Patients achieving at least partial response (PR) will proceed to consolidative low-dose WBRT (23.4 Gy in 13 fractions), followed by maintenance selinexor (80 mg orally once weekly) until disease progression or unacceptable toxicity. The primary endpoint is the overall response rate (ORR) based on the Lugano 2014 criteria. Secondary endpoints include complete response rate (CRR), progression-free survival (PFS), overall survival (OS), and safety/tolerability assessed by CTCAE v5.0. A total of 26 patients will be enrolled. This study aims to provide an effective treatment option for transplant-ineligible CNSL patients and to explore the potential synergistic effects of selinexor with chemotherapy and radiotherapy.

Conditions

• Lymphomas

Interventions

Type	Name	Description
DRUG	Selinexor + High-dose Methotrexate + Rituximab + WBRT	Rituximab 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.

Timeline

• Start date: 2025-06-01
• Primary completion: 2028-12-30
• Completion: 2028-12-31
• First posted: 2025-06-03
• Last updated: 2025-06-03

Locations

1 site across 1 country: China