Selinexor in Combination With R-CHOP as the First-line Therapy for TP53-mutated DLBCL Patients (Smart Trial)
- Conditions
- Diffuse Large B Cell Lymphoma
- Interventions
- Drug: R-CHOP Protocol
- Registration Number
- NCT06517511
- Lead Sponsor
- Sun Yat-sen University
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 42
- Subjects fully understand and voluntarily participate in this study and sign informed consent.
- Aged ≥18, and ≤70 years, no gender limitation.
- Patient was histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL) and had TP53 mutations.
- 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.
Key
- DLBCL combined with other types of lymphoma. Transformed DLBCL.
- 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.
- The investigators think that the patient is not suitable for the study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Selinexor in combination with R-CHOP Selinexor Oral Tablet [Xpovio] 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. Selinexor in combination with R-CHOP R-CHOP Protocol 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.
- Primary Outcome Measures
Name Time Method Complete response rate (CRR) Up to 8 cycles (each cycle is 21 days) To investigate the preliminary anti-tumor efficacy
- Secondary Outcome Measures
Name Time Method 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 To investigate the preliminary anti-tumor efficacy
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 To investigate the preliminary anti-tumor efficacy
Overall survival (OS) 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
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 To identify the incidence of AE and SAE
Duration of response (DOR) 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
Time to response (TTR) From the date of enrollment until the first response, assessed up to 24 weeks To investigate the preliminary anti-tumor efficacy
Objective response rate (ORR) Up to 8 cycles (each cycle is 21 days) To investigate the preliminary anti-tumor efficacy
Trial Locations
- Locations (2)
Sun yat-sen university cancer center
🇨🇳Guangzhou, Guangdong, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, Shanghai, China