PET and EBV DNA-directed Therapy for Localized Nasal Extranodal NK/T Cell Lymphoma
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 89
- 试验地点
- 1
- 主要终点
- 2-year progression-free survival rate
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 <
- •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.
排除标准
- •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.
研究组 & 干预措施
Interim PET and EBV DNA-directed therapy
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.
干预措施: 4 cycles of ESA regimen with sandwiched radiotherapy (Drug)
Interim PET and EBV DNA-directed therapy
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.
干预措施: 2 cycles of ESA regimen sequential radiotherapy and 2 cycles of PD-1 monoclonal antibody combined with pegaspargase (Drug)
Interim PET and EBV DNA-directed therapy
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.
干预措施: 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 (Drug)
结局指标
主要结局
2-year progression-free survival rate
时间窗: Baseline up to data cut-off (up to approximately 2 years)
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.
次要结局
- Treatment-Related Adverse Events rate as assessed by CTCAE version 5.0(From enrollment to study completion, a maximum of 3 years)
- Changes of plasma EBV DNA load(From enrollment to study completion, a maximum of 3 years)
- 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(Baseline up to data cut-off (up to approximately 2 years))
- 2-year overall survival rate(Baseline up to data cut-off (up to approximately 2 years))
- Objective response rate(End of treatment (6-8 weeks after last cycle))
- Complete response rate(End of treatment (6-8 weeks after last cycle))
研究者
Zhao Weili
First Deputy Director, Hematology Department
Ruijin Hospital