Overview
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.
Description
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.
Eligibility
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.
