Clinical trial NCT06517511: Selinexor in Combination With R-CHOP as the First-line Therapy for TP53-mutated DLBCL Patients (Smart Trial)
Official 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Diffuse Large B Cell Lymphoma
Keywords: TP53-mutated diffuse large B-cell lymphoma
Selinexor
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: Fudan University
First posted: 2024-07-24
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed 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 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.

Primary outcomes:
measure: Complete response rate (CRR)
timeFrame: Up to 8 cycles (each cycle is 21 days)
Secondary outcomes:
measure: Disease-free survival (DFS)
timeFrame: 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
measure: Objective response rate (ORR)
timeFrame: Up to 8 cycles (each cycle is 21 days)
measure: Progression-free survival (PFS)
timeFrame: 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
measure: Overall survival (OS)
timeFrame: From the date of enrollment until the date of death from ant cause, assessed up to 24 months
measure: Number of participants with adverse events (AE) and severe adverse events (SAE) as assessed by CTCAE v5.0
timeFrame: Through study completion, an average of 2 years
measure: Duration of response (DOR)
timeFrame: From date of the first CR or PR to the first documented progressive disease or death, whichever occurred earlier, assessed up to 24 months
measure: Time to response (TTR)
timeFrame: From the date of enrollment until the first response, assessed up to 24 weeks
Other outcomes:
measure: The gene mutations such as DDX3X、TET2、PTPN2 and so on are sequenced by whole genome sequencing
timeFrame: Through study completion, an average of 2 years
measure: The RNA alterations are sequenced by transcriptome sequencing
timeFrame: Through study completion, an average of 2 years
measure: Genetic classification of DLBCL
timeFrame: Through study completion, an average of 2 years
Locations:
city: Guangzhou
country: China
facility: Sun yat-sen university cancer center
state: Guangdong
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
affiliation: Sun yat-sen university cancer cente
name: QingQing Cai, MD. PhD.
role: PRINCIPAL_INVESTIGATOR
affiliation: Sun yat-sen university cancer cente
name: Yi Xia, MD. PhD.
role: PRINCIPAL_INVESTIGATOR
affiliation: Fudan University
name: Rong Tao, MD.
role: PRINCIPAL_INVESTIGATOR
References: