Combination treatment for relapse refractory central nervous system lymphoma

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 clinical trial investigates the efficacy and safety of a combination regimen involving Selinexor, Methotrexate, and Rituximab in patients with relapse refractory primary and secondary central nervous system lymphoma. The study consists of a dose escalation phase followed by a phase 2 expansion, enrolling approximately 30 patients. Participants will receive escalating doses of Selinexor alongside standard treatments, with a total of six treatment cycles planned. The trial aims to assess the tolerability and effectiveness of this novel combination therapy.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* Patients must meet all of the following inclusion criteria to be eligible to enroll in this study:

  1. Participants must be able to understand and be willing to sign a written informed consent document.
  2. Men and woman who are 18-75 years old on the day of consenting to the study.
  3. Histologically documented PCNSL and SCNSL secondary to histologically documented systemic diffuse large B-cell lymphoma (DLBCL).
  4. Patients must have relapsed/refractory PCNSL or relapsed/refractory SCNSL.
  5. Patients must have response or remain stable disease for 2 months to prior methotrexate-based regimen.
  6. Patients who had prior autologous hematopoietic stem cell transplantation are eligible.
  7. Patients with parenchymal lesions must have unequivocal evidence of disease progression on imaging (MRI of the brain or head CT) 28 days prior to cycle1 day 1(C1D1). For patients with leptomeningeal disease only, CSF cytology must document lymphoma cells.
  8. Participants must have an Eastern Cooperative Oncology Group performance status of 0-3.
  9. Participants must have adequate bone marrow and organ function shown by:

     1. Absolute neutrophil count (ANC) ≥ 1.0 x 10\^9/L
     2. Platelets ≥ 75 x 10\^9/L and no platelet transfusion within the past 14 days prior to study registration c Hemoglobin (Hgb) ≥ 8 g/dL and no red blood cell (RBC) transfusion within the past 14 days prior to study registration
  10. International Normalized Ratio (INR) ≤ 1.5 and PTT (aPTT) ≤ 1.5 times the upper limit of normal.
  11. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal.
  12. Serum bilirubin ≤ 1.5 times the upper limit of normal; or total bilirubin ≤ 3 times the upper limit of normal with direct bilirubin within the normal range in patients with well documented Gilbert Syndrome.
  13. Calculated creatinine clearance(CrCl)≥50ml/min using the Cockcroft-Gault equation or 24-hour urine collection.
  14. Life expectancy of \> 3 months.

Exclusion Criteria:

1. Patients with SCNSL actively receiving treatment for extra-CNS disease are excluded.
2. Lymphoma patients with only intraocular involvement.
3. Pathological diagnosis of PCNSL is T-cell lymphoma.
4. Patients with disease progression within 6 months of prior methotrexate-containing regimen.
5. patients only had received stereotactic radiation therapy as prior treatment.
6. Patients have received chemotherapy, monoclonal antibodies or targeted anticancer therapy within 21 days or 5 half-lives, whichever is shorter, prior to C1D1.
7. Patients with active, unstable cardiovascular diseases, fits any of the following:

   1. myocardial infarction within 6 months prior to the study enrollment
   2. unstable angina within 3 months prior to the study enrollment
   3. Uncontrolled clinically-significant conduction abnormalities (e.g., ventricular tachycardia, ventricular fibrillation, etc.)
   4. Congestive heart failure (CHF) of New York Heart Association (NYHA) ≥ Grade 3
   5. Echocardiography showing left ventricular ejection fraction less than 50%
8. Uncontrolled active infection within 1 week prior to the first dose of study drug.
9. Known active hepatitis B, or C infection or HIV infection; Note: Hepatitis B virus (HBV) surface antigen (HBsAg) and or hepatitis B core antibody-positive but undetectable HBV DNA or Hepatitis C virus (HCV) antibody positive but hepatitis C virus RNA undetectable are allowed.
10. Active GI dysfunction interfering with the ability to swallow tablets, or any GI dysfunction that could interfere with absorption of study treatment.
11. Prior exposure to a selective inhibitor of nuclear export(SINE) compound, including selinexor.
12. Serious, active psychiatric, or medical conditions which, in the opinion of the Investigator, could interfere with study treatment.

Where it's running

• Department of Hematology, Huashan Hospital, Fudan University
  Shanghai, Shanghai Municipality, China Recruiting
• The First Affiliated Hospital Of Anhui Medical University
  Hefei, Anhui, China Not yet recruiting
• Beijing Tiantan Hospital, Capital Medical University
  Beijing, Beijing Municipality, China Not yet recruiting
• The First Affiliated Hospital Of Fujian Medical University
  Fuzhou, Fujian, China Not yet recruiting
• Oncology Department of The First Affiliated Hospital of Zhengzhou University
  Zhengzhou, Henan, China Not yet recruiting

Study contacts

• Principal investigator: Tong Chen, Ph.D — Huashan Hospital
• Study coordinator: Tong Chen, Ph.D
• Email: chentong@fudan.edu.cn
• Phone: +862152887102

Similar studies

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

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• 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

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

  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.

  Recruiting Phase 2 Second Affiliated Hospital of Soochow University · Suzhou · NCT07002099

• 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

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.