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

NCT06517511 | Recruiting Phase 2

• 1 other identifier: B2024-333-01
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Diffuse Large B Cell Lymphoma

Keywords

TP53-mutated diffuse large B-cell lymphoma; Selinexor

Outcome Measures

Primary Outcomes (1)

• Complete response rate (CRR)

  To investigate the preliminary anti-tumor efficacy

  Up to 8 cycles (each cycle is 21 days)

Secondary Outcomes (7)

• Disease-free survival (DFS)

  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

• Objective response rate (ORR)

  Up to 8 cycles (each cycle is 21 days)

• Progression-free survival (PFS)

  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

• Overall survival (OS)

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

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

  Through study completion, an average of 2 years

Other Outcomes (3)

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

  Through study completion, an average of 2 years

• The RNA alterations are sequenced by transcriptome sequencing

  Through study completion, an average of 2 years

• Genetic classification of DLBCL

  Through study completion, an average of 2 years

Study Arms (1)

Selinexor in combination with R-CHOP

EXPERIMENTAL

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.

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

Interventions

Selinexor Oral Tablet [Xpovio] DRUG

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

Also known as: exportin 1 (XPO1) inhibitor

Selinexor in combination with R-CHOP

R-CHOP Protocol DRUG

Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone

Also known as: R-CHOP regimen

Selinexor in combination with R-CHOP

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Fudan University: collaborator

Study Sites (2)

Sun yat-sen university cancer center

Guangzhou, Guangdong, 510060, China

RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

selinexor; Exportin 1 Protein; R-CHOP protocol

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Karyopherins; Nucleocytoplasmic Transport Proteins; Membrane Transport Proteins; Carrier Proteins; Proteins; Amino Acids, Peptides, and Proteins; Membrane Proteins; Nuclear Proteins; Receptors, Cytoplasmic and Nuclear

Study Officials

• QingQing Cai, MD. PhD.

  Sun yat-sen university cancer cente

  PRINCIPAL INVESTIGATOR

• Yi Xia, MD. PhD.

  Sun yat-sen university cancer cente

  PRINCIPAL INVESTIGATOR

• Rong Tao, MD.

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

QingQing Cai, MD. PhD.

CONTACT

0086-20-87342823; caiqq@sysucc.org.cn

Yi Xia, MD. PhD.

CONTACT

0086-20-87342823; xiayi@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: chief physician

Study Record Dates

• First Submitted: July 14, 2024
• First Posted: July 24, 2024
• Study Start: August 1, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: February 12, 2026

Record last verified: 2026-01

Locations

CN (2)