Selinexor in Combination With R-CHOP as the First-line Therapy for TP53-mutated DLBCL Patients (Smart Trial)

Selinexor in Combination With R-CHOP as the First-line Therapy for TP53-mutated DLBCL Patients: a Single-arm, Multicenter, Phase II Clinical Trial (Smart Trial)

This is a prospective, single-arm, multi-center, phase II clinical trial to evaluate the efficacy and safety of selinexor in combination with R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisone) followed by selinexor maintenance for untreated TP53-mutated diffuse large B-cell lymphoma (DLBCL) patients.

The purpose of this phase II clinical trial is to evaluate the efficacy and safety of selinexor in combination with R-CHOP for untreated TP53-mutated DLBCL patients.

The induction phase consisted of 8 cycles of selinexor in combination with R-CHOP. After 8 cycles of induction therapy, if the response is assessed as complete remission (CR), maintenance therapy with selinexor will be conducted.

The primary endpoint is complete response rate.

Inclusion Criteria:

• Subjects fully understand and voluntarily participate in this study and sign informed consent.
• Aged ≥18 and ≤80 years, no gender limitation.
• Histologically confirmed DLBCL with TP53 mutations (allowing transformed or concurrent indolent B-cell non-Hodgkin lymphoma)
• No prior systemic anti-lymphoma therapy; prior local radiotherapy alone is permitted.
• There must be at least one measurable or evaluable lesion that meets the evaluation criteria for Lugano 2014 lymphoma.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2.
• Expected survival ≥ 3 months.
• Adequate function of bone marrow, liver, and kidney.

Exclusion Criteria:

• DLBCL with Hodgkin lymphoma, T-cell lymphoma, or other non-B-cell lymphoma; Richter transformation.
• DLBCL with central nervous system invasion.
• The patients had previously received XPO1 inhibitors.
• The patients have contraindications to any drug in the combined treatment.
• Patients with chronic active hepatitis B or active hepatitis C. If the background hepatitis B surface antigen (HBsAg) and/or hepatitis B core Antibody (HBcAb) or hepatitis C Virus (HCV) antibody are positive, the further determination for Hepatitis B Virus (HBV) DNA (no more than 2500 copies /mL or 500 IU/mL) and HCV RNA (no more than the lower limit of the assay) can be included. The patients with HBsAg and/or HBcAb positive need to receive anti-HBV drugs.
• Patients with the infection of human immunodeficiency virus (HIV) and/or acquired immunodeficiency syndrome.
• Inability to swallow tablets, presence of malabsorption syndrome, or any other gastrointestinal disease or dysfunction that may affect the absorption of the study drug.
• Pregnant and lactating women and subjects of childbearing age who do not want to use contraception.
• Mentally ill persons or persons unable to obtain informed consent.
• Any condition deemed unsuitable by the investigator.