Selinexor in Combination With MTX+Ritu to Treat R/R CNSL

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.