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NCT Number: NCT06517511

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

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Key information

Conditions

Diffuse Large B Cell Lymphoma Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Lymphatic Diseases Lymphoma Lymphoma, B-Cell Lymphoma, Large B-Cell, Diffuse Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Sun yat-sen university cancer center, Guangzhou, Guangdong, China

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Selinexor Oral Tablet [Xpovio]

Drug

Selinexor (60mg po D1, 8) is added from the second cycle of R-CHOP regimen.

Other names: exportin 1 (XPO1) inhibitor

R-CHOP Protocol

Drug

Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone

Other names: R-CHOP regimen

Primary outcomes

  1. Complete response rate (CRR)

    Time frame: Up to 8 cycles (each cycle is 21 days)

    To investigate the preliminary anti-tumor efficacy

Secondary outcomes

  1. Disease-free survival (DFS)

    Time frame: From date of the first complete response until the date of the first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

    To investigate the preliminary anti-tumor efficacy

  2. Objective response rate (ORR)

    Time frame: Up to 8 cycles (each cycle is 21 days)

    To investigate the preliminary anti-tumor efficacy

  3. Progression-free survival (PFS)

    Time frame: From the date of enrollment until the date of the first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

    To investigate the preliminary anti-tumor efficacy

  4. Overall survival (OS)

    Time frame: From the date of enrollment until the date of death from ant cause, assessed up to 24 months

    To investigate the preliminary anti-tumor efficacy

  5. Number of participants with adverse events (AE) and severe adverse events (SAE) as assessed by CTCAE v5.0

    Time frame: Through study completion, an average of 2 years

    To identify the incidence of AE and SAE

  6. Duration of response (DOR)

    Time frame: From date of the first CR or PR to the first documented progressive disease or death, whichever occurred earlier, assessed up to 24 months

    To investigate the preliminary anti-tumor efficacy

  7. Time to response (TTR)

    Time frame: From the date of enrollment until the first response, assessed up to 24 weeks

    To investigate the preliminary anti-tumor efficacy

Other outcomes

  1. The gene mutations such as DDX3X、TET2、PTPN2 and so on are sequenced by whole genome sequencing

    Time frame: Through study completion, an average of 2 years

    To explore the correlations between gene mutations and response and prognosis

  2. The RNA alterations are sequenced by transcriptome sequencing

    Time frame: Through study completion, an average of 2 years

    To explore the correlations between RNA alterations and response and prognosis

  3. Genetic classification of DLBCL

    Time frame: Through study completion, an average of 2 years

    To explore the correlations between genetic classification of DLBCL and response and prognosis

Study contacts

Contact information is provided by the study sponsor or research team.

QingQing Cai, MD. PhD.

CONTACT

[email protected]

0086-20-87342823

Yi Xia, MD. PhD.

CONTACT

[email protected]

0086-20-87342823

Sponsors and collaborators

Lead sponsor

Sun Yat-sen University

Other

Collaborators

  • Fudan University

Registry information

Official study title

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)

Important dates

Study start
2024
Primary completion
2027
Study completion
2028
First posted
Jul 24, 2024
Registry last updated
Feb 12, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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