P-Gemoxd Regimen Followed by Radiotherapy Versus P-CHOP Regimen Followed by Radiotherapy in ENKTL With Early Stage: a Randomized, Multicenter, Open-label, Phase 2 Study
试验速览
- 阶段
- 2 期
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Objective response rate（complete remission rate + partial remission rate）
研究概览
简要总结
Extranodal natural killer/T-cell lymphoma (ENKTL) is an aggressive subtype of non-Hodgkin's lymphoma and shows extremely poor survival. Several retrospective studies and singe-arm prospective phase 2 studies have shown that pegaspargase combined Gemox or CHOP regimen achieved a promising efficacy in treatment of ENKTL. However, there is no prospective study to compare the efficacy of these two regimens. This prospective pilot study to compare the efficacy and safety of the P-Gemoxd chemotherapy regimen with those of the P-CHOP regimen for stage IE to IIE ENKTL.
详细描述
Treatment PA-Gemoxd dosages were as follows: days 1 and 5, 30-min intravenous infusion of 800 mg/m2 gemcitabine; day 1, 2-h intravenous infusion of 85 mg/m2 oxaliplatin; day 1, deep intramuscular injection of 2000 U/m2 PEG-ASP at four different sites; d1-5, intravenous infusion of 15mg dexamethasone. The regimen was repeated every 3 weeks for four cycles followed by involved-field radiotherapy after got CR, PR or SD. Three-dimensional conformal radiotherapy was done by linear accelerator at 2.0 grays (Gy) per daily fraction with 5-6 weeks. The involved- field radiation (IFRT) dose was 50-56 Gy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •pathologically confirmed, previously untreated ENKTL with stage I/II (for stage I, the patients should have one of the following risk factors: EBV-DNA > upper limit of normal, lesions beyond nasal, fever, LDH elevation);
- •age range from 18 to 70 years;
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
- •at least one measurable lesion;
- •adequate haematologic function (haemoglobin > 8.0 g/l, absolute neutrophil count > 1500/ml, platelets > 75,000/l),
- •adequate hepatic function (total serum bilirubin ≤ 1.5 times the upper limit of normal, alanine aminotransferase and aspartate aminotransferase ≤ 2.5 times the upper limit of normal),
- •Hepatitis B virus carriers should have normal HBV-DNA copies and should use antiviral drugs. For patients with elevated HBV-DNA, should use antiviral drugs until the HBV-DNA decrease to < the upper limit of normal.
- •adequate renal function (serum creatinine ≤ 1.5 mg/dl, creatinine clearance ≥ 50 ml/min);
- •normal coagulation function and electrocardiogram results.
- •Prior chemotherapy and radiotherapy should have been completed >4 weeks earlier,
- •willingness to provide written informed consent.
排除标准
- •mismatch the inclusion criteria
- •systematic central nervous system involvement, previous or concomitant malignancies and any coexisting medical problems that could cause poor compliance with the study protocol.
- •primary lesion not from the upper respiratory
研究组 & 干预措施
P-Gemoxd
Pegaspargase+Gemcitabine+Oxaliplatin+Dexamethasone (PEG-ASP+Gemoxd): Patients received the P-Gemoxd chemotherapy regimen every 3 weeks.
Pegaspargase 2000U/m2 im day 1, Gemcitabine 800mg/m2 ivdrip 30min day 1 and day 5, Oxaliplatin 85mg/m2 ivdrip day 1, Dexamethasone 15 mg ivdrip, QD, day 1 to day 5.
IMRT：IMRT is delivered using 6-8 MeV linear accelerator using intensity-modulated radiation treatment planning. The radiation dose is 50 -56grays (Gy) in 25-28 fractions.
干预措施: pegaspargase (Drug)
P-Gemoxd
Pegaspargase+Gemcitabine+Oxaliplatin+Dexamethasone (PEG-ASP+Gemoxd): Patients received the P-Gemoxd chemotherapy regimen every 3 weeks.
Pegaspargase 2000U/m2 im day 1, Gemcitabine 800mg/m2 ivdrip 30min day 1 and day 5, Oxaliplatin 85mg/m2 ivdrip day 1, Dexamethasone 15 mg ivdrip, QD, day 1 to day 5.
IMRT：IMRT is delivered using 6-8 MeV linear accelerator using intensity-modulated radiation treatment planning. The radiation dose is 50 -56grays (Gy) in 25-28 fractions.
干预措施: Gemcitabine (Drug)
P-Gemoxd
Pegaspargase+Gemcitabine+Oxaliplatin+Dexamethasone (PEG-ASP+Gemoxd): Patients received the P-Gemoxd chemotherapy regimen every 3 weeks.
Pegaspargase 2000U/m2 im day 1, Gemcitabine 800mg/m2 ivdrip 30min day 1 and day 5, Oxaliplatin 85mg/m2 ivdrip day 1, Dexamethasone 15 mg ivdrip, QD, day 1 to day 5.
IMRT：IMRT is delivered using 6-8 MeV linear accelerator using intensity-modulated radiation treatment planning. The radiation dose is 50 -56grays (Gy) in 25-28 fractions.
干预措施: Oxaliplatin (Drug)
P-Gemoxd
Pegaspargase+Gemcitabine+Oxaliplatin+Dexamethasone (PEG-ASP+Gemoxd): Patients received the P-Gemoxd chemotherapy regimen every 3 weeks.
Pegaspargase 2000U/m2 im day 1, Gemcitabine 800mg/m2 ivdrip 30min day 1 and day 5, Oxaliplatin 85mg/m2 ivdrip day 1, Dexamethasone 15 mg ivdrip, QD, day 1 to day 5.
IMRT：IMRT is delivered using 6-8 MeV linear accelerator using intensity-modulated radiation treatment planning. The radiation dose is 50 -56grays (Gy) in 25-28 fractions.
干预措施: Dexamethasone (Drug)
P-Gemoxd
Pegaspargase+Gemcitabine+Oxaliplatin+Dexamethasone (PEG-ASP+Gemoxd): Patients received the P-Gemoxd chemotherapy regimen every 3 weeks.
Pegaspargase 2000U/m2 im day 1, Gemcitabine 800mg/m2 ivdrip 30min day 1 and day 5, Oxaliplatin 85mg/m2 ivdrip day 1, Dexamethasone 15 mg ivdrip, QD, day 1 to day 5.
IMRT：IMRT is delivered using 6-8 MeV linear accelerator using intensity-modulated radiation treatment planning. The radiation dose is 50 -56grays (Gy) in 25-28 fractions.
干预措施: IMRT (Radiation)
P-CHOP
Pegaspargase+Cyclophosphamide+Doxorubicin+Vincristine +Prednisone (P-CHOP)：Patients received the P-CHOP chemotherapy regimen every 3 weeks. Cyclophosphamide 750 mg/m2，ivdrip day 1； doxorubicin 50mg/m 2，ivdrip day 1；vincristine 1.4 mg/m 2(≤2mg），ivdrip day 1; Pegaspargase 2000U/m2 im，day 2 and prednisone (60 mg/m 2 /day) on days 1 to 5 orally.
IMRT is delivered using 6-8 MeV linear accelerator using intensity-modulated radiation treatment planning. The radiation dose is 50-56 grays (Gy) in 25-28 fractions.
干预措施: pegaspargase (Drug)
P-CHOP
Pegaspargase+Cyclophosphamide+Doxorubicin+Vincristine +Prednisone (P-CHOP)：Patients received the P-CHOP chemotherapy regimen every 3 weeks. Cyclophosphamide 750 mg/m2，ivdrip day 1； doxorubicin 50mg/m 2，ivdrip day 1；vincristine 1.4 mg/m 2(≤2mg），ivdrip day 1; Pegaspargase 2000U/m2 im，day 2 and prednisone (60 mg/m 2 /day) on days 1 to 5 orally.
IMRT is delivered using 6-8 MeV linear accelerator using intensity-modulated radiation treatment planning. The radiation dose is 50-56 grays (Gy) in 25-28 fractions.
干预措施: Cyclophosphamide (Drug)
P-CHOP
Pegaspargase+Cyclophosphamide+Doxorubicin+Vincristine +Prednisone (P-CHOP)：Patients received the P-CHOP chemotherapy regimen every 3 weeks. Cyclophosphamide 750 mg/m2，ivdrip day 1； doxorubicin 50mg/m 2，ivdrip day 1；vincristine 1.4 mg/m 2(≤2mg），ivdrip day 1; Pegaspargase 2000U/m2 im，day 2 and prednisone (60 mg/m 2 /day) on days 1 to 5 orally.
IMRT is delivered using 6-8 MeV linear accelerator using intensity-modulated radiation treatment planning. The radiation dose is 50-56 grays (Gy) in 25-28 fractions.
干预措施: Doxorubicin (Drug)
P-CHOP
Pegaspargase+Cyclophosphamide+Doxorubicin+Vincristine +Prednisone (P-CHOP)：Patients received the P-CHOP chemotherapy regimen every 3 weeks. Cyclophosphamide 750 mg/m2，ivdrip day 1； doxorubicin 50mg/m 2，ivdrip day 1；vincristine 1.4 mg/m 2(≤2mg），ivdrip day 1; Pegaspargase 2000U/m2 im，day 2 and prednisone (60 mg/m 2 /day) on days 1 to 5 orally.
IMRT is delivered using 6-8 MeV linear accelerator using intensity-modulated radiation treatment planning. The radiation dose is 50-56 grays (Gy) in 25-28 fractions.
干预措施: Vincristine (Drug)
P-CHOP
Pegaspargase+Cyclophosphamide+Doxorubicin+Vincristine +Prednisone (P-CHOP)：Patients received the P-CHOP chemotherapy regimen every 3 weeks. Cyclophosphamide 750 mg/m2，ivdrip day 1； doxorubicin 50mg/m 2，ivdrip day 1；vincristine 1.4 mg/m 2(≤2mg），ivdrip day 1; Pegaspargase 2000U/m2 im，day 2 and prednisone (60 mg/m 2 /day) on days 1 to 5 orally.
IMRT is delivered using 6-8 MeV linear accelerator using intensity-modulated radiation treatment planning. The radiation dose is 50-56 grays (Gy) in 25-28 fractions.
干预措施: Prednisone (Drug)
P-CHOP
Pegaspargase+Cyclophosphamide+Doxorubicin+Vincristine +Prednisone (P-CHOP)：Patients received the P-CHOP chemotherapy regimen every 3 weeks. Cyclophosphamide 750 mg/m2，ivdrip day 1； doxorubicin 50mg/m 2，ivdrip day 1；vincristine 1.4 mg/m 2(≤2mg），ivdrip day 1; Pegaspargase 2000U/m2 im，day 2 and prednisone (60 mg/m 2 /day) on days 1 to 5 orally.
IMRT is delivered using 6-8 MeV linear accelerator using intensity-modulated radiation treatment planning. The radiation dose is 50-56 grays (Gy) in 25-28 fractions.
干预措施: IMRT (Radiation)
结局指标
主要结局
Objective response rate（complete remission rate + partial remission rate）
时间窗: every 6 weeks,up to completion of treatment (approximately 6 months)
The criteria for the efficacy evaluation (overall response rate and complete remission) of the regimen is according to the following article: Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014 Sep 20;32(27):3059-68.
progression free survival
时间窗: up to end of follow-up-phase (approximately 3 years)
time from the date of enrollment to date of disease progression, or death of any cause, or date of lost follow-up, whichever comes first
overall survival
时间窗: up to end of follow-up-phase (approximately 3 years)
overall survival (OS): time from the date of enrollment to date of death from any cause, or date of lost follow-up, whichever comes first
次要结局
- Incidence of Treatment-Emergent Adverse Events according to Common Terminology Criteria for Adverse Events v3.0(every 3 weeks,up to completion of treatment (approximately 6 months))