Diffuse Large B Cell Lymphoma
Conditions
Keywords
TP53-mutated diffuse large B-cell lymphoma, Selinexor
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.
Interventions
DRUGSelinexor Oral Tablet [Xpovio]
Selinexor (60mg po D1, 8) is added from the second cycle of R-CHOP regimen.
DRUGR-CHOP Protocol
Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone
Sponsors
Sun Yat-sen University
Fudan University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete response rate (CRR) | Up to 8 cycles (each cycle is 21 days) | To investigate the preliminary anti-tumor efficacy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Objective response rate (ORR) | Up to 8 cycles (each cycle is 21 days) | 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 |
Countries
China
Contacts
CONTACTQingQing Cai, MD. PhD.
CONTACTYi Xia, MD. PhD.
PRINCIPAL_INVESTIGATORQingQing Cai, MD. PhD.
Sun yat-sen university cancer cente
PRINCIPAL_INVESTIGATORYi Xia, MD. PhD.
Sun yat-sen university cancer cente
PRINCIPAL_INVESTIGATORRong Tao, MD.
Fudan University
Outcome results
None listed