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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 (Smart Trial)

Recruiting
18-70 years
All
Phase 2

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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

Key Inclusion Criteria:

  1. Subjects fully understand and voluntarily participate in this study and sign informed consent.
  2. Aged ≥18, and ≤70 years, no gender limitation.
  3. Patient was histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL) and had TP53 mutations.
  4. There must be at least one measurable or evaluable lesion that meets the evaluation criteria for Lugano 2014 lymphoma.
  5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2.
  6. Expected survival ≥ 3 months.
  7. Adequate function of bone marrow, liver, and kidney.

Key Exclusion Criteria:

  1. DLBCL combined with other types of lymphoma. Transformed DLBCL.
  2. DLBCL with central nervous system invasion.
  3. The patients had previously received XPO1 inhibitors.
  4. The patients have contraindications to any drug in the combined treatment.
  5. 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.
  6. Patients with the infection of human immunodeficiency virus (HIV) and/or acquired Immunodeficiency syndrome.
  7. Inability to swallow tablets, presence of malabsorption syndrome, or any other gastrointestinal disease or dysfunction that may affect the absorption of the study drug.
  8. Pregnant and lactating women, and subjects of childbearing age who do not want to use contraception.
  9. Mentally ill persons or persons unable to obtain informed consent.
  10. The investigators think that the patient is not suitable for the study.

Study details
    Diffuse Large B Cell Lymphoma

NCT06517511

Sun Yat-sen University

22 August 2025

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