A Multicenter, Randomized, Cross-over Phase 3 Comparing Preventive Pegylated Filgrastim and Filgrastim in Cancer Patients Receiving Myelosuppressive Chemotherapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 337
- 主要终点
- Protective rate of grade 4 neutropenia
研究概览
简要总结
Neutropenia is one of the most frequent adverse effects of chemotherapy, and the main factor to limit the dosage and delay the schedule of chemotherapy. Preventive filgrastim administration has long been established as the standard of care. A pegylated filgrastim was independently developed by GeneLeuk Biopharmaceutical Co., Ltd, Shandong, China. It composed of filgrastim and a 20 kd polyethylene glycol molecule covalently bound at the N-terminal residue. Preclinical studies phase 1 and phase 2 trials have shown that pegylated filgrastim has decreased renal clearance, increased plasma half-life, and prolonged efficacy in compare with filgrastim. These characters were similar to those of Neulasta.
The investigators designed a multicenter, randomized, cross-over phase Ⅲ trial to compare the efficacy and safety of a single injection of pegylated filgrastim and daily injections of filgrastim in chemotherapy naive patients receiving commonly used regimens. The hypothesis is that pegylated filgrastim is similarly effective and safe with regular filgrastim.
详细描述
This was a multicenter, randomized, open-label, cross-over, noninferiority study to evaluate whether a single injection of pegfilgrastim is as effective and safe as daily injections of filgrastim in patients receiving commonly used chemotherapy regimens. Patients were randomly assigned in a 1:1 ratio to AOB and BOA arm with center as the stratification variables. All the patients received two cycles of chemotherapy of identical regimen and dosage. In arm AOB, patients were administered pegylated filgrastim 100 ug/kg in cycle 1 and filgrastim 5 ug/kg/d in cycle 2; while in arm BOA, patients received filgrastim 5 ug/kg/d in cycle 1 and pegylated filgrastim 100 ug/kg in cycle 2.
Study drugs Both filgrastim and pegylated filgrastim were provided by GeneLeuk Biopharmaceutical Co., Ltd, Shandong, China.
In cycle 1 of AOB arm and cycle 2 of BOA arm, on 9 am of day 3, patients were to receive a dose of 100µg/kg of pegylated filgrastim, based on actual body weight, as a single s.c. injection.
In cycle 2 of AOB arm and cycle 1 of BOA arm, patients were to receive daily s.c. injection of filgrastim at a dose of 5 µg/kg/day. Injections began on 9 am of day 3 and continued daily until an absolute neutrophil count (ANC) ≥10.0 × 109 /l was documented after the expected nadir or for a maximum of 14 days, whichever occurred first.
Chemotherapy Treatment All cytotoxic agents were administrated on day 1 of the 21-day regimens. The regimens include PC(paclitaxel 175 mg/m2; carboplatin area under curve[AUC] 5～6 or cisplatin 75 mg/m2 )； AC (doxorubicin [or pirarubicin]60 mg/m2 or epirubicin 100 mg/m2；cyclophosphamide 600 mg/m2), PA(paclitaxel 175 mg/m2 ；doxorubicin [or pirarubicin]50 mg/m2 or epirubicin 80 mg/m2）； CHOP (cyclophosphamide 750mg/m2；doxorubicin[or pirarubicin] 50 mg/m2 or epirubicin100 mg/m2；vincristine1.4 mg/m2；prednisone 100mg，po，day 1-5)。 Efficacy measurements Blood samples were collected for complete blood counts (cbc) with differential on days 0, 3, 5, 7, 9, 11, 13, 17 and 21 of each cycle. Day 0 was defined as the day before day one, in cycle 1 it is the base line, and in cycle 2 is day 21 of cycle 1.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Supportive Care
- 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
- •diagnosis of malignant solid tumours (excluding highly aggressive lymphomas such as lymphoblastic lymphoma and Burkitt lymphoma)
- •chemotherapy naive
- •Karnofsky Performance Status ≥70
- •age 18-70 years; normal white blood cell (WBC) count and platelet count
- •adequate renal, hepatic and cardiac function
- •life expectancy ≥3 months
- •normal bone marrow function
排除标准
- •history of systematic chemotherapy (including adjuvant therapy)
- •large area radiotherapy (>25% of bone marrow volume)
- •uncontrolled infection
- •bone marrow involvement
- •pregnancy, lactation
- •history of blood stem cell or organ transplantation
- •antibiotic administration within 72 hours of enrolment
- •long time exposure to glucocorticoids and immunosuppressive agents
研究组 & 干预措施
AOB,pegylated filgrastim to filgrastim
patients were administered pegylated filgrastim 100 ug/kg in cycle 1 and filgrastim 5 ug/kg/d in cycle 2
干预措施: pegylated filgrastim and filgrastim (Drug)
BOA,filgrastim to pegylated filgrastim
patients received filgrastim 5 ug/kg/d in cycle 1 and pegylated filgrastim 100 ug/kg in cycle 2
干预措施: filgrastim and pegylated filgrastim (Drug)
结局指标
主要结局
Protective rate of grade 4 neutropenia
时间窗: 21 days
the rate of ANC keeps above 0.5 × 109 /l through the whole cycle
次要结局
- rate of grade 3/4 neutropenia(21 days)
- time to neutrophil recovery(21 days)
- incidence of antibiotic administration(21 days)
- ANC profile(21 days)
- incidence and severity adverse events(21 days)
- incidence and severity of side effects(21 days)
- changes in clinical laboratory values(21 days)
- incidence of febrile neutropenia(21 days)