Clinical trial NCT05833893: Clinical Study of XPO1 Inhibitor Selinexor Combined With COPL in Newly Diagnosed Advanced NK/T-cell Lymphoma
Official title: Clinical Study of XPO1 Inhibitor Selinexor Combined With COPL in Newly Diagnosed Advanced NK/T-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: nk/T-cell Lymphoma
Newly Diagnosed
Advanced Lymphoma
Lead sponsor: Chinese PLA General Hospital
Sponsor class: OTHER
First posted: 2023-04-27
Enrollment: 10
Sex: ALL
Minimum age (years): 14
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: response rate
timeFrame: 1-year
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: 1-year
Secondary outcomes:
measure: the 1-year PFS
timeFrame: 1-year
measure: the 1-year OS
timeFrame: 1-year
measure: the ctDNA and EBV copy number in peripheral blood
timeFrame: 1-year
Other outcomes:
Locations:
city: Beijing
country: China
facility: ChinaPLAGH
state: Haidian
Study officials:
affiliation: Chief
name: Yu Zhao, Graduate
role: PRINCIPAL_INVESTIGATOR
affiliation: Attending doctor
name: Sai Huang, Graduate
role: PRINCIPAL_INVESTIGATOR
References:
citation: Benkova K, Mihalyova J, Hajek R, Jelinek T. Selinexor, selective inhibitor of nuclear export: Unselective bullet for blood cancers. Blood Rev. 2021 Mar;46:100758. doi: 10.1016/j.blre.2020.100758. Epub 2020 Sep 15.
citation: Tse E, Kwong YL. Diagnosis and management of extranodal NK/T cell lymphoma nasal type. Expert Rev Hematol. 2016 Sep;9(9):861-71. doi: 10.1080/17474086.2016.1206465. Epub 2016 Jul 8.
citation: Lim SH, Hong JY, Lim ST, Hong H, Arnoud J, Zhao W, Yoon DH, Tang T, Cho J, Park S, Ko YH, Kim SJ, Suh C, Lin T, Kim WS. Beyond first-line non-anthracycline-based chemotherapy for extranodal NK/T-cell lymphoma: clinical outcome and current perspectives on salvage therapy for patients after first relapse and progression of disease. Ann Oncol. 2017 Sep 1;28(9):2199-2205. doi: 10.1093/annonc/mdx316.