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

Sun Yat-sen University

Status and phase: Enrolling; Phase 2

Conditions: Diffuse Large B Cell Lymphoma

Treatments: Drug: R-CHOP Protocol; Drug: Selinexor Oral Tablet [Xpovio]

Study type: Interventional

Funder types: Other

Identifiers

NCT06517511

B2024-333-01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 42 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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42 participants in 1 patient group

Selinexor in combination with R-CHOP

Experimental group

Description:

Patients with TP53-mutated diffuse large B-cell lymphoma will receive selinexor in combination with R-CHOP regimen from the second cycle of R-CHOP (3 weeks per cycle). After 8 cycles of induction therapy, if the response is assessed as complete remission (CR), maintenance therapy with selinexor will be conducted.

Treatment:

Drug: R-CHOP Protocol

Drug: Selinexor Oral Tablet [Xpovio]