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PET and EBV DNA-directed Therapy for Localized Nasal Extranodal NK/T Cell Lymphoma (ENKTL)

Primary Purpose

NK-T-Cell Lymphoma, Extranodal

Status
Not yet recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
4 cycles of ESA regimen with sandwiched radiotherapy
2 cycles of ESA regimen sequential radiotherapy and 2 cycles of PD-1 monoclonal antibody combined with pegaspargase
2 cycles of ESA regimen, 2 cycles of PD-1 monoclonal antibody and concurrent radiotherapy, 2 cycles of PD-1 monoclonal antibody combined with pegaspargase
Sponsored by
Ruijin Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for NK-T-Cell Lymphoma, Extranodal

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Pathologically newly diagnosed extranodal NK/T cell lymphoma, nasal type (according to the WHO classification 2016); No previous anti-lymphoma treatment; Age ≥ 18 years old; Ann Arbor stage I/II; ECOG 0-2 score; Patients with a life expectancy of at least 3 months; At least one measurable / evaluable lesion from diagnostic biopsy to the beginning of treatment; Sufficient bone marrow and liver and kidney function, namely: Absolute neutrophil count (ANC)> 1000 / μL, platelet count> 50, 000 / μl, hemoglobin> 9g/ dl; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <3 times the upper limit of normal (ULN); Serum total bilirubin <1. 5 times ULN (patients with Gilbert syndrome can be included); Serum creatinine <2 times ULN or creatinine clearance rate> 50 ml/min. Able to comply with the research procedures and cooperate in the implementation of the entire research process; Written informed consent; Women with fertility agree to take appropriate measures to avoid pregnancy during the treatment period until at least one year after the end of treatment; Men agree to maintain abstinence or use barrier contraception. Exclusion Criteria: Diagnosed invasive NK cell leukemia and extranasal ENKTL; Ann Arbor stage III/IV; Pregnant or lactation; Autoimmune diseases that require systemic treatment in the past 2 years (namely, antirheumatic drugs, hormones or immunosuppressants), including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome related vascular thrombosis, Wegener's granuloma, Sjogren's syndrome, Guillain Barre syndrome, multiple sclerosis, vasculitis or glomerulonephritis. The following cases are allowed to be included: autoimmune hypothyroidism or type I diabetes receiving stable treatment, hormone replacement treatment (such as thyroxine, insulin, or supplement of physiological hormone due to insufficient adrenal or pituitary gland) are not considered as systematic treatment and are allowed to be included. Other invasive cancers that have not received curative treatment or are still receiving anti-cancer treatment (including hormone therapy for breast cancer or prostate cancer) in the past 3 years; Pneumonia requiring steroid medication treatment (non-infectious); Or had clinical evidence of interstitial lung disease or active and non-infectious pneumonia; Active infections that require systemic treatment; Severe cardiovascular disease, or myocardial infarction, unstable arrhythmia, or unstable angina pectoris occurring 3 months ago; Previous treatment with anti PD-1, anti PD-L1, or anti PD-L2 drugs; HBsAg, HCV, or HIV positivity; HBV and HCV serological positivity is allowed, but DNA/RNA must be negative; Live attenuated vaccine vaccination within 4 weeks before the treatment; patients are prohibited from receiving live attenuated vaccines during the study period, including influenza vaccines; Central nervous system diseases; Previous allogeneic tissue/solid organ transplantation; Active tuberculosis; Other concurrent uncontrollable medical conditions that may interfere the participation of the study.

Sites / Locations

  • Ruijin Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Interim PET and EBV DNA-directed therapy

Arm Description

According to the interim PET and EBV DNA results, patients are divided into three cohorts: 1) cohort A: Deauville score 1-3 and EBV DNA negativity; 2) cohort B: Deauville score 1-3 and EBV DNA positivity; 3) cohort C: Deauville score 4-5.

Outcomes

Primary Outcome Measures

2-year progression-free survival rate
Progression-free survival was defined as the time from the date of randomization until the date of the first disease progression or relapse, using 2014 Lugano criteria, or death from any cause, whichever occurred first.

Secondary Outcome Measures

2-year overall survival rate
Overall survival was defined as the time from the date of randomization to the date of death from any cause.
2-year PFS and OS rates in the subgroups of interim Deauville score 1-3 with EBV DNA negative, Deauville 1-3 with EBV DNA positive, and Deauville 4-5
PFS was progression-free survival; OS was overall survival.
Objective response rate
Percentage of participants with complete response and partial response was determined on the basis of investigator assessments according to 2014 Lugano criteria.
Complete response rate
Percentage of participants with complete response was determined on the basis of investigator assessments according to 2014 Lugano criteria.
Treatment-Related Adverse Events rate as assessed by CTCAE version 5.0
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Changes of plasma EBV DNA load
Plasma EBV DNA load monitoring

Full Information

First Posted
September 29, 2023
Last Updated
September 29, 2023
Sponsor
Ruijin Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT06069830
Brief Title
PET and EBV DNA-directed Therapy for Localized Nasal Extranodal NK/T Cell Lymphoma
Acronym
ENKTL
Official Title
PET and EBV DNA-directed Therapy for Localized Nasal Extranodal NK/T Cell Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 2023 (Anticipated)
Primary Completion Date
October 2026 (Anticipated)
Study Completion Date
October 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ruijin Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
A prospective, open-abel, phase 2 clinical study to investigate whether interim Positron Emission Tomography (PET) and Epstein-Barr virus (EBV) DNA-directed therapy can improve the prognosis of localized nasal extranodal NK/T cell lymphoma (ENKTL) patients.
Detailed Description
This study aims to evaluate the significance of mid-term PET and EBV DNA-directed therapy for localized nasal ENKTL. Patients receive 2 cycles of ESA (Pegaspargase, Etoposide, Dexamethasone) regimen, then according to the mid-term PET and EBV DNA results, patients are divided into three cohorts: 1) cohort A: patients with Deauville score 1-3 and EBV DNA negative receive sequential radiotherapy and 2 cycles of ESA regimen; 2) cohort B: patients with Deauville score 1-3 and EBV DNA positive receive sequential radiotherapy and 2 cycles of PD-1 monoclonal antibody combined with pegaspargase; 3) cohort C: patients with Deauville score 4-5 receive 2 cycles of PD-1 monoclonal antibody and concurrent radiotherapy, then 2 cycles of PD-1 monoclonal antibody combined with pegaspargase.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
NK-T-Cell Lymphoma, Extranodal

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
89 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Interim PET and EBV DNA-directed therapy
Arm Type
Experimental
Arm Description
According to the interim PET and EBV DNA results, patients are divided into three cohorts: 1) cohort A: Deauville score 1-3 and EBV DNA negativity; 2) cohort B: Deauville score 1-3 and EBV DNA positivity; 3) cohort C: Deauville score 4-5.
Intervention Type
Drug
Intervention Name(s)
4 cycles of ESA regimen with sandwiched radiotherapy
Intervention Description
Pegaspargase, 2500U/m2, i.m. d1; etoposide, 200mg, p.o., d2-d4; Dexamethasone, 40mg, p.o. d2-d4；
Intervention Type
Drug
Intervention Name(s)
2 cycles of ESA regimen sequential radiotherapy and 2 cycles of PD-1 monoclonal antibody combined with pegaspargase
Intervention Description
Pegaspargase, 2500U/m2, IM, d1; PD-1 monoclonal antibody, 200mg, i.v. d2;
Intervention Type
Drug
Intervention Name(s)
2 cycles of ESA regimen, 2 cycles of PD-1 monoclonal antibody and concurrent radiotherapy, 2 cycles of PD-1 monoclonal antibody combined with pegaspargase
Intervention Description
PD-1 monoclonal antibody, 200mg, i.v. d1
Primary Outcome Measure Information:
Title
2-year progression-free survival rate
Description
Progression-free survival was defined as the time from the date of randomization until the date of the first disease progression or relapse, using 2014 Lugano criteria, or death from any cause, whichever occurred first.
Time Frame
Baseline up to data cut-off (up to approximately 2 years)
Secondary Outcome Measure Information:
Title
2-year overall survival rate
Description
Overall survival was defined as the time from the date of randomization to the date of death from any cause.
Time Frame
Baseline up to data cut-off (up to approximately 2 years)
Title
2-year PFS and OS rates in the subgroups of interim Deauville score 1-3 with EBV DNA negative, Deauville 1-3 with EBV DNA positive, and Deauville 4-5
Description
PFS was progression-free survival; OS was overall survival.
Time Frame
Baseline up to data cut-off (up to approximately 2 years)
Title
Objective response rate
Description
Percentage of participants with complete response and partial response was determined on the basis of investigator assessments according to 2014 Lugano criteria.
Time Frame
End of treatment (6-8 weeks after last cycle)
Title
Complete response rate
Description
Percentage of participants with complete response was determined on the basis of investigator assessments according to 2014 Lugano criteria.
Time Frame
End of treatment (6-8 weeks after last cycle)
Title
Treatment-Related Adverse Events rate as assessed by CTCAE version 5.0
Description
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time Frame
From enrollment to study completion, a maximum of 3 years
Title
Changes of plasma EBV DNA load
Description
Plasma EBV DNA load monitoring
Time Frame
From enrollment to study completion, a maximum of 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Pathologically newly diagnosed extranodal NK/T cell lymphoma, nasal type (according to the WHO classification 2016); No previous anti-lymphoma treatment; Age ≥ 18 years old; Ann Arbor stage I/II; ECOG 0-2 score; Patients with a life expectancy of at least 3 months; At least one measurable / evaluable lesion from diagnostic biopsy to the beginning of treatment; Sufficient bone marrow and liver and kidney function, namely: Absolute neutrophil count (ANC)> 1000 / μL, platelet count> 50, 000 / μl, hemoglobin> 9g/ dl; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <3 times the upper limit of normal (ULN); Serum total bilirubin <1. 5 times ULN (patients with Gilbert syndrome can be included); Serum creatinine <2 times ULN or creatinine clearance rate> 50 ml/min. Able to comply with the research procedures and cooperate in the implementation of the entire research process; Written informed consent; Women with fertility agree to take appropriate measures to avoid pregnancy during the treatment period until at least one year after the end of treatment; Men agree to maintain abstinence or use barrier contraception. Exclusion Criteria: Diagnosed invasive NK cell leukemia and extranasal ENKTL; Ann Arbor stage III/IV; Pregnant or lactation; Autoimmune diseases that require systemic treatment in the past 2 years (namely, antirheumatic drugs, hormones or immunosuppressants), including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome related vascular thrombosis, Wegener's granuloma, Sjogren's syndrome, Guillain Barre syndrome, multiple sclerosis, vasculitis or glomerulonephritis. The following cases are allowed to be included: autoimmune hypothyroidism or type I diabetes receiving stable treatment, hormone replacement treatment (such as thyroxine, insulin, or supplement of physiological hormone due to insufficient adrenal or pituitary gland) are not considered as systematic treatment and are allowed to be included. Other invasive cancers that have not received curative treatment or are still receiving anti-cancer treatment (including hormone therapy for breast cancer or prostate cancer) in the past 3 years; Pneumonia requiring steroid medication treatment (non-infectious); Or had clinical evidence of interstitial lung disease or active and non-infectious pneumonia; Active infections that require systemic treatment; Severe cardiovascular disease, or myocardial infarction, unstable arrhythmia, or unstable angina pectoris occurring 3 months ago; Previous treatment with anti PD-1, anti PD-L1, or anti PD-L2 drugs; HBsAg, HCV, or HIV positivity; HBV and HCV serological positivity is allowed, but DNA/RNA must be negative; Live attenuated vaccine vaccination within 4 weeks before the treatment; patients are prohibited from receiving live attenuated vaccines during the study period, including influenza vaccines; Central nervous system diseases; Previous allogeneic tissue/solid organ transplantation; Active tuberculosis; Other concurrent uncontrollable medical conditions that may interfere the participation of the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Weili Zhao
Phone
+862164370045
Email
zwl_trial@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Pengpeng Xu
Phone
+862164370045
Email
pengpeng_xu@126.com
Facility Information:
Facility Name
Ruijin Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200020
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Weili Zhao
Phone
+862164370045
Ext
610707
Email
zwl_trial@163.com

12. IPD Sharing Statement

Learn more about this trial

PET and EBV DNA-directed Therapy for Localized Nasal Extranodal NK/T Cell Lymphoma

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