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

Sponsor
Second Affiliated Hospital of Soochow University
Study ID
NCT07002099
Phase
PHASE2
Status
Recruiting
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Conditions

  • Lymphomas

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Selinexor + High-dose Methotrexate + Rituximab + WBRT — DRUG
    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.

Study Details

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.

Key Dates

Start date
Jun 1, 2025
Status verified
May 2025
Primary completion
Dec 30, 2028
Completion
Dec 31, 2028

Study Design

Enrollment
26 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Experimental Arm
    Participants in this single-arm study will receive combination therapy as follows: 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. After radiotherapy, patients who maintain a response will continue with maintenance selinexor 80 mg orally once weekly until disease progression, unacceptable toxicity, or withdrawal. This arm is designed to assess the synergistic effect of selinexor when combined with standard CNSL chemotherapy and radiotherapy in patients who are not eligible for stem cell transplantation.

Primary Outcome Measure

ORR [ Time Frame: 2 years ]

Central Contacts

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