Clinical Study of XPO1 Inhibitor Selinexor Combined With COPL in Newly Diagnosed Advanced NK/T-cell Lymphoma

Study Overview
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Brief Summary
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Patients with newly diagnosed, pathologically confirmed NK/T-cell lymphoma of stage III-IV treated with XCOPL regimen. 3 weeks for a cycle, with a total of 6-8 cycles.

Detailed Description
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Patients with newly diagnosed, pathologically confirmed NK/T-cell lymphoma of stage III-IV treated with XCOPL regimen. 3 weeks for a cycle, with a total of 6-8 cycles. Initial safety and PET-CT assessment were performed after 3 cycles of treatment (which could be delayed until 4 cycles of treatment in special cases). Patients who achieved partial remission or above will continue the original regimen, and patients who did not achieve partial remission or above will perform re-biopsy and be excluded from the group. Patients who remain partial remission by PET-CT evaluation after 6 cycles may switch to a second-line regimen (referring to NCCN guidelines, GDP regimen combined with selinexor is recommended). Chemotherapy will be performed for up to 8 cycles (followed by autologous or allogeneic hematopoietic stem cell transplantation), after which follow-up period was entered. It is recommended to perform ultrasound or CT evaluation, peripheral blood ctDNA and EBV copy number every three months during the first year of follow-up, and PET-CT evaluation every half a year.

Official Title
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Clinical Study of XPO1 Inhibitor Selinexor Combined With COPL in Newly Diagnosed Advanced NK/T-cell Lymphoma

Conditions
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nk/T-cell Lymphoma, Newly Diagnosed, Advanced Lymphoma

Intervention / Treatment
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* Drug: XPO1 inhibitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age≥14 years, male or female; Pathologically confirmed newly diagnosed NK/T cell lymphoma according to WHO classification criteria 2016; At least one measurable lesion, defined as bidimensionally measurable, intranodal lesion > 1.5 cm in short axis and extranodal lesion > 1.0 cm in short axis; ECOG score 0 2; Clinical stage III IV; Normal major organ function, meeting the following definitions: Hematology: WBC ≥ 3.5 x 10 9/L, PLT ≥ 75 x 10 9/L, Hb ≥ 80 g/L; Liver and kidney function: AST and ALT ≤ 3.0 ULN; TBIL ≤ 2.0 mg/dL; CCr ≥ 60 mL/min; liver and kidney function impairment caused by tumor compression is not limited by this; Fibrinogen: normal at first cycle Expected survival > 6 months Agree to use effective contraception; Understand and voluntarily sign written informed consent Exclusion Criteria: Prior allogeneic HCT (allo-HCT) Active autoimmune disease Primary central nervous system lymphoma; Patients with infection which requiring treatment. Could be re-enrollment after infection control; Known history of human immunodeficiency virus (HIV) infection Known hypersensitivity to the study drug or any of its excipients; Presence of other active malignancy requiring treatment that could interfere with this study; Patients with other conditions not suitable for enrollment as judged by the investigator.

Ages Eligible for Study
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Minimum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group<br>COPL + XPO1 inhibitor (Selinexor, 60 mg, po., d1,8,15) | Drug: XPO1 inhibitor<br>* COPL + XPO1 inhibitor (Selinexor, 60 mg, po., d1,8,15)<br>* Other names: COPL;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| response rate | complete remission + partial remission | 1-year | 
| Incidence of Treatment-Emergent Adverse Events | Incidence of Treatment-Emergent Adverse Events | 1-year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the 1-year PFS | To evaluate the 1-year PFS of XCOPL regimen in advanced NK/T-cell lymphoma | 1-year | 
| the 1-year OS | To evaluate the 1-year OS of XCOPL regimen in advanced NK/T-cell lymphoma | 1-year | 
| the ctDNA and EBV copy number in peripheral blood | To evaluate the feasibility of measurable residual disease (MRD) detection and clinical recurrence prediction by ctDNA and EBV copy number. | 1-year |