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

Launched by TONG CHEN, MD · Jan 15, 2023

Keywords

ClinConnect Summary

This clinical trial is investigating a new treatment approach for patients with a type of brain cancer called primary central nervous system lymphoma (PCNSL). The study is testing a combination of three medications: selinexor (ATG-010), methotrexate, and rituximab, to see if this combination can help patients whose cancer has not responded to previous treatments. The trial aims to enroll about 30 participants, who will receive escalating doses of selinexor along with the other two drugs. The goal is to determine the best dose that is both safe and effective.

To be eligible for the trial, participants need to be between 18 and 75 years old and have a confirmed diagnosis of PCNSL that has either relapsed or has not responded to treatment. They should also have shown some response or stability after previous methotrexate treatment. Participants will be closely monitored for how well they tolerate the treatment and any side effects. It's important for potential participants to understand that this is an early-phase study, meaning it's one of the first steps in testing a new treatment, and they will receive detailed information about their involvement and what to expect throughout the trial.

Gender

ALL

Eligibility criteria

• 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.