Selinexor with high-dose methotrexate, rituximab, and low-dose whole-brain radiotherapy for newly diagnosed CNS lymphoma patients who can't have transplant

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

We will test whether adding oral selinexor to high-dose methotrexate and rituximab followed by low-dose whole-brain radiotherapy can help people with newly diagnosed central nervous system lymphoma who are not candidates for stem cell transplant.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 26 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Second Affiliated Hospital of Soochow University (Academic / other)
• Drugs / interventions: rituximab, chemotherapy, radiation, methotrexate
• Locations: 1 site (Suzhou)
• Trial ID: NCT07002099 on ClinicalTrials.gov

What this trial studies

This open-label, single-arm phase II trial enrolls adults with newly diagnosed primary or secondary CNS lymphoma who are ineligible for autologous stem cell transplant. Participants receive up to six 21-day cycles of rituximab, high-dose methotrexate, and weekly oral selinexor, with tumor response assessed every three cycles. Patients achieving at least a partial response proceed to consolidative low-dose whole-brain radiotherapy (23.4 Gy in 13 fractions) and then continue selinexor maintenance until disease progression or unacceptable toxicity. The trial will measure overall response rate, progression-free survival, overall survival, and safety.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed primary or secondary CNS lymphoma confined to the CNS, measurable disease or positive CSF, ECOG 0-3, adequate organ function, and judged ineligible for autologous stem cell transplant are the intended participants.

Not a fit: Patients who are eligible for and prefer standard intensive therapies including autologous stem cell transplant, those with uncontrolled systemic lymphoma outside the CNS, severe organ dysfunction, or who are pregnant are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could improve disease control while offering a less intensive, potentially better-tolerated option for patients who cannot undergo stem cell transplant.

How similar studies have performed: Selinexor has shown activity in hematologic malignancies and preclinical data suggest it can sensitize lymphoma cells to chemotherapy and radiation, but combining selinexor with high-dose methotrexate and WBRT in newly diagnosed CNS lymphoma is novel and clinical data are limited.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 18 years, male or female.
2. Histologically confirmed primary CNS lymphoma (PCNSL) or secondary CNS lymphoma (SCNSL) with CNS-only involvement.
3. Ineligible for autologous stem cell transplantation based on clinical assessment or patient refusal.
4. At least one measurable brain lesion ≥1 cm in diameter, or positive cerebrospinal fluid (CSF) cytology/flow cytometry for patients with leptomeningeal disease.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-3.
6. Adequate organ function, including:

   * Absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L
   * Platelets ≥ 75 × 10⁹/L
   * Hemoglobin ≥ 80 g/L
   * Total bilirubin ≤ 1.5 × ULN (or ≤ 3 × ULN if liver involvement)
   * ALT and AST ≤ 2.5 × ULN (or ≤ 5 × ULN if liver involvement)
   * Creatinine clearance ≥ 30 mL/min (Cockcroft-Gault formula)
   * INR ≤ 1.5 × ULN; APTT within 10 seconds of normal
7. Estimated life expectancy of ≥ 3 months.
8. Negative serum pregnancy test for women of childbearing potential.
9. Ability to understand and willingness to sign a written informed consent form.

Exclusion Criteria:

1. CNS involvement limited to intraocular lymphoma only.
2. Prior systemic therapy for CNS lymphoma.
3. SCNSL with active systemic (non-CNS) disease involvement.
4. Uncontrolled intracranial hypertension.
5. Clinically significant or unstable cardiovascular disease, including:

   * Myocardial infarction within 6 months
   * Unstable angina within 3 months
   * Uncontrolled arrhythmias (e.g., ventricular tachycardia/fibrillation)
   * Congestive heart failure NYHA class ≥ III
   * LVEF \< 50% by echocardiography
6. Other severe uncontrolled medical conditions, including active infections requiring systemic therapy.
7. Known active hepatitis B (HBV), hepatitis C (HCV), or HIV infection.
8. Active gastrointestinal dysfunction that interferes with the ability to swallow or absorb oral medication.
9. Prior treatment with selective inhibitor of nuclear export (SINE) compounds, including selinexor.
10. Concurrent malignancy, except for adequately treated basal/squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ of the cervix, prostate, or breast.
11. Pregnant or breastfeeding women, or subjects unwilling to use medically accepted effective contraception during the study and for 6 months after the last dose.
12. Any condition which, in the investigator's judgment, would make the patient unsuitable for study participation.

Where this trial is running

Suzhou

• The Second Affiliated Hospital of Soochow University — Suzhou, China (Recruiting)

Study contacts

• Principal investigator: Bingzong Li — Second Affiliated Hospital of Soochow University
• Study coordinator: Bingzong Li

Conditions Lymphomas; Selinexor; central nervous system lymphoma; WBRT