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

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Lymphoma; Newly Diagnosed; nk/T-cell Lymphoma
• Intervention / Treatment: Drug: XPO1 inhibitor

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.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yu Zhao, Graduate; Phone Number: 010-66937232; Email: zhaoyu301@126.com
• Study Contact Backup: Name: Sai Huang, Graduate; Phone Number: 010-66937232; Email: helinahs@qq.com

Study Locations

• China
  • Haidian
    • Beijing, Haidian, China, 100853
      • Recruiting
      • ChinaPLAGH
      • Contact: Yu Zhao, Graduate; Phone Number: 010-66937232
      • Contact: Sai Huang, Graduate; Phone Number: 010-66937232

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group; COPL + XPO1 inhibitor (Selinexor, 60 mg, po., d1,8,15)	Drug: XPO1 inhibitor; COPL + XPO1 inhibitor (Selinexor, 60 mg, po., d1,8,15); Other Names: COPL

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital
• Investigators: Principal Investigator: Yu Zhao, Graduate, Chief; Principal Investigator: Sai Huang, Graduate, Attending doctor

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2023
• Primary Completion (Anticipated): December 31, 2025
• Study Completion (Anticipated): December 31, 2026

Study Registration Dates

• First Submitted: February 25, 2023
• First Submitted That Met QC Criteria: April 18, 2023
• First Posted (Actual): April 27, 2023

Study Record Updates

• Last Update Posted (Actual): April 27, 2023
• Last Update Submitted That Met QC Criteria: April 18, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral
• Other Study ID Numbers: XCOPL - NK/T -P01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Clinical study of XPO1 inhibitor Selinexor combined with COPL in newly diagnosed advanced NK/T-cell lymphoma

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No