Treatment with the drug Selinexor for relapsed/refractory DLBCL when no other standard treatment options are available

Diffuse large B-cell lymphoma (DLBCL) is a form of non-Hodgkin lymphoma that affects B lymphocytes, a subtype of white blood cells that are part of the immune system. In DLBCL, rapid enlargement of the lymph nodes and spread to other organs may occur. Other symptoms include fever, night sweats, and weight loss, among others. The exact cause of DLBCL is unknown, but genetic changes and infections such as the Epstein-Barr virus (EBV) may play a role. DLBCL often occurs as a new diagnosis, but it can also develop from another pre-existing lymphoma. Patients with newly diagnosed DLBCL are typically treated with a combination of chemotherapy and immunotherapy, such as R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). An autologous stem cell transplant is also often part of the standard treatment. If the disease cannot be controlled with therapy (refractory) or if the disease becomes active again (relapse), the treatment regimen is changed. Several treatment options are now available for this situation; however, it is possible that none of these therapies will provide adequate treatment.

This Phase 2b study is investigating the appropriate dosage, efficacy, and safety of selinexor as a monotherapy. Selinexor is a medication that acts by specifically targeting the cell nucleus of the affected cells and can induce cancer cell death. Selinexor is already approved for the treatment of relapsed or refractory DLBCL. In Part 1 of the study, patients receive 60 mg of selinexor twice a week for a total of 4 weeks. In Part 2 of the study, researchers first determine whether patients have a history of stem cell transplantation. Based on this, patients are divided into two subgroups. Subsequently, patients are randomly assigned to two groups of 55 people each for further treatment. Once again, patients receive selinexor twice a week for a total of 4 weeks. The single dose of Selinexor is 40 mg in Group 1 and 60 mg in Group 2. The study is open-label, meaning that both the medical staff and the patients know which medication and dose are being administered. Treatment and monitoring as part of the study will continue until the disease progresses again or the patient dies. During this period, the study will evaluate the efficacy of the treatment and the occurrence of side effects associated with the various medications. The primary endpoint of the study is the overall response rate to treatment. Patients aged 18 and older with DLBCL are eligible to participate in this study. The disease must be refractory to initial treatment or have recurred, and patients must have no other treatment options available with proven clinical benefit. Patients must have already received treatment with the antibody rituximab, and the brain must not be affected.