Selinexor Combined With R-GemOx as Second-line Treatment in Patients With Diffuse Large B-cell Lymphoma

Study Overview
=================
Brief Summary
-----------------
The goal of this interventional study is to evaluate efficiency and safety in prior one-line treated diffuse large B-cell lymphoma. The main questions it aims to answer are: Complete remission rate Objective remission rate Progression-free survival tolerance Participants will recevied a minimum of 2 and a maximum of 6 cycles of R-GemOx(rituximab 375 mg/m2 IV on day 1 , Gemcitabine 1000 mg/m2, Oxaliplatin 100 mg/m2 IV on day 2) and 60 mg selinexor on days 1, 8, and 15 of each cycle

Detailed Description
-----------------
After the subject has completed at least 2 courses of treatment with Serenixol and R-GemOx for up to 6 courses, the patients who have reached ≥ partial remission (PR) and meet the conditions of transplantation can receive transplantation according to the institutional standards, and those who are not suitable for transplantation can receive maintenance treatment with Serenixol. In the maintenance treatment, the dose of Serenixol is 60 mg on the first day of the week until the disease progresses In case of intolerable toxicity or if the researcher believes that the patient is no longer suitable for study treatment, re-examine every 3 months in the first year, the second year and every 6 months after the end of transplantation or maintenance treatment; Patients with stable disease (SD) or disease progression (PD) after 2 6 courses of treatment will end the trial, and no survival follow-up will be conducted

Official Title
-----------------
Selinexor Combined With R-GemOx as Second-line Treatment in Patients With Diffuse Large B-cell Lymphoma： a Single-arm, Single-centre, Open-label Trial

Conditions
-----------------
Diffuse Large B-Cell Lymphoma, Not Otherwise Specified

Intervention / Treatment
-----------------
* Drug: selinexor


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Have pathologically confirmed CD20 positive de novo DLBCL or DLBCL transformed from previously diagnosed indolent lymphoma (e.g., follicular lymphoma) HIV-seropositive Age 18-75 years ECOG PS≤2 Positron emission tomography (PET) positive measurable disease with at least one node having the longest diameter (LDi)>1.5cm or one extranodal lesion with LDi>1cm (per the Lugano Criteria 2014) (Documentation to be provided) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 × Upper limit of normal value (ULN), or ≤ 5 in the presence of known lymphoma involving the liver × ULN; Total serum bilirubin ≤ 2 × ULN, or ≤ 5 when Gilbert syndrome or known lymphoma affects the liver × ULN; Creatinine clearance (CrCl) calculated according to Cockcroft Gault formula ≥ 30 mL/min; Absolute neutrophil count (ANC)≥1.5×10^9/L,or Platelet count≥75×10^9/L(No platelet were transfused within 14 days before the treatment of the study drug),or Hemoglobin≥80g/L(No red blood cells were transfused within 14 days before the treatment of the study drug) Written informed consent in accordance with federal, local, and institutional guidelines Patients understanding the characteristics of the disease and voluntarily joins the study program for treatment and follow-up No other serious diseases in conflict with this program Investigator believe that subjects can benefit Exclusion Criteria: Patients with known central nervous system involvement by lymphoma; Patients with a history of autoimmune diseases or syndrome requiring systemic use of steroid, such as hypophysitis, pneumonia, colitis, hepatitis, nephritis, hyperthyroidism and hypothyroidism Patients received systemic glucocorticoid (prednisone >20mg/d) or any other immunosuppressive therapy within 7 days before the first administration,excluding nasal spray inhalation or other topical glucocorticoids; Uncontrolled heart diseases, including unstable angina pectoris, acute myocardial infarction 6 months before randomization, congestive heart failure (NYHA), cardiac function grade greater than grade III or IV, or left ventricular ejection fraction<50%; Patients previously treated with selinexor; History of severe allergic reactions (as determined by treating physician) attributed to the drugs being used in the study; Patients undergoing organ transplantation; Diagnosed as malignant tumor other than lymphoma or receiving treatment,excluding: Malignant tumors that have received treatment for the purpose of cure and have not developed known active diseases for ≥ 5 years before enrollment Basal cell carcinoma of the skin (excluding melanoma) with adequate treatment and no signs of disease Cervical carcinoma in situ with adequate treatment and no signs of disease Patients with grade 2 or more neurotoxicity occurred within two weeks before treatment; Severe infection; Drug abuse, medical psychological or social conditions that may interfere with the subject's participation in the study or the evaluation of the results of the study; Any active, serious psychiatric, medical, or other conditions/situations which, in the treating physician's opinion, could compromise the patient's safety

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Patients will receive selinexor PO on days 1, 8, and 15 of a 21 week cycle. R-GemOx will be given at standard dosing every 21 days | Drug: selinexor<br>* Given PO<br>* Other names: KPT-330;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission rate | Response rates will be estimated as proportions with 95% Wilson confidence intervals | UP to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | PFS will be described with Kaplan-Meier curves and estimated medians with 95% confidence intervals | From baseline to disease progression or death from any cause, assessed up to 2 years | 
| Objective remission rate | Response rates will be estimated as proportions with 95% Wilson confidence intervals | UP to 2 years |