Combination treatment for relapse refractory central nervous system lymphoma
Selinexor in Combination With Methotrexate and Rituximab for Relapsed /Refractory Central Nervous System (CNS) Lymphoma
This study is testing a new combination of three medications to see if it can help people with hard-to-treat central nervous system lymphoma feel better.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 30 (estimated) |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Sponsor | Huashan Hospital Academic / other |
| Drugs / interventions | chemotherapy, radiation, methotrexate, Rituximab |
| Locations | 5 sites (Hefei, Anhui and 4 other locations) |
| Trial ID | NCT05698147 on ClinicalTrials.gov |
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.
Who should consider this trial
Good fit: Ideal candidates include adults aged 18-75 with histologically confirmed relapse refractory primary or secondary central nervous system lymphoma.
Not a fit: Patients who do not have relapse refractory central nervous system lymphoma or those with significant comorbidities may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat central nervous system lymphoma.
How similar studies have performed: While there have been studies on similar combination therapies, this specific approach with Selinexor is relatively novel and has not been extensively tested.
Eligibility criteria
Show full inclusion / exclusion 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.
Where this trial is running
Hefei, Anhui and 4 other locations
- 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)
- Department of Hematology, Huashan Hospital, Fudan University — Shanghai, Shanghai Municipality, China (Recruiting)
Study contacts
- Principal investigator: Tong Chen, Ph.D — Huashan Hospital
- Study coordinator: Tong Chen, Ph.D
- Email: chentong@fudan.edu.cn
- Phone: +862152887102
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.