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

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

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 it's running

• 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
• Email: lbzwz0907@hotmail.com
• Phone: 86-512-67784069

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• R-PMDT Regimen for Newly Diagnosed PCNSL

  This study tests the R-PMDT treatment approach in people newly diagnosed with primary CNS lymphoma to see how many respond.

  Recruiting Phase 2 Institute of Hematology & Blood Diseases Hospital, China · Tianjin · NCT07604987

• PD‑1 blocker with rituximab, high‑dose methotrexate, and orelabrutinib for newly diagnosed primary or secondary CNS lymphoma

  This trial will test whether combining a PD‑1 blocker with rituximab, high‑dose methotrexate, and orelabrutinib helps people with newly diagnosed primary or secondary central nervous system diffuse large B‑cell lymphoma.

  Recruiting Phase 2 The First Affiliated Hospital with Nanjing Medical University · Nanjing, Jiangsu · NCT07410520

• Testing a four-drug regimen (methotrexate, rituximab, sintilimab, pirtobrutinib) versus investigator-selected care for newly diagnosed PCNSL

  This trial will try a combination of methotrexate, rituximab, sintilimab and pirtobrutinib as first treatment for adults with newly diagnosed primary central nervous system lymphoma to see if it increases complete remissions and is safe compared with standard doctor-selected treatments.

  Recruiting at 3 sites Phase 2 Tongji Hospital · Xiamen, Fujian and 3 other locations · NCT07350850

• Orelabrutinib Combined With Teniposide, Rituximab and Methotrexate for Newly Diagnosed PCNSL

  In this study, adults with newly diagnosed primary CNS lymphoma try different induction regimens to see which one works best before consolidation therapy.

  Recruiting at 9 sites Phase 2/3 Huashan Hospital · Beijing and 14 other locations · NCT07185373

• ZR-MTX combo for newly diagnosed primary intraocular lymphoma

  This trial tests a Rituximab, Zanubrutinib, and methotrexate cocktail plus intravitreal methotrexate in people newly diagnosed with primary intraocular lymphoma to see if it can extend the time before the disease progresses.

  Recruiting Phase 2 Peking Union Medical College Hospital · Beijing, Beijing Municipality · NCT06973811

• New treatment approach for primary central nervous system lymphoma

  This study is testing a new combination of treatments for people with newly diagnosed primary central nervous system lymphoma to see if it can help them respond better and stay healthy longer.

  Recruiting The First Hospital of Jilin University · Changchun · NCT06946407

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.