Clinical trial NCT06069830: PET and EBV DNA-directed Therapy for Localized Nasal Extranodal NK/T Cell Lymphoma
Official title: PET and EBV DNA-directed Therapy for Localized Nasal Extranodal NK/T Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: NK-T-Cell Lymphoma, Extranodal
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
First posted: 2023-10-06
Enrollment: 89
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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:

  1. Absolute neutrophil count (ANC)\> 1000 / μL, platelet count\> 50, 000 / μl, hemoglobin\> 9g/ dl;
  2. 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);
  3. 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.

Primary outcomes:
measure: 2-year progression-free survival rate
timeFrame: Baseline up to data cut-off (up to approximately 2 years)
Secondary outcomes:
measure: 2-year overall survival rate
timeFrame: Baseline up to data cut-off (up to approximately 2 years)
measure: 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
timeFrame: Baseline up to data cut-off (up to approximately 2 years)
measure: Objective response rate
timeFrame: End of treatment (6-8 weeks after last cycle)
measure: Complete response rate
timeFrame: End of treatment (6-8 weeks after last cycle)
measure: Treatment-Related Adverse Events rate as assessed by CTCAE version 5.0
timeFrame: From enrollment to study completion, a maximum of 3 years
measure: Changes of plasma EBV DNA load
timeFrame: From enrollment to study completion, a maximum of 3 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ruijin Hospital
state: Shanghai
Study officials:
References: