Safety and Efficacy of Stem Cell Mobilization Using G-CSF (Filgrastim) Alone Compared to Intermediate-dose Cytosine Arabinoside Plus G-CSF in Hodgkin's Lymphoma and Non-Hodgkin's Lymphoma Patients.
试验速览
- 阶段
- 3 期
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- • The proportion of patients with stem cell yield at least 2 × 10^6 CD34+ cells/kg in each treatment arm.
研究概览
简要总结
The purpose of the study is to compare safety and efficacy of stem cell mobilization using G-CSF (filgrastim) alone vs. intermediate-dose cytosine arabinoside plus G-CSF in Hodgkin's lymphoma and non-Hodgkin's lymphoma patients.
详细描述
Autologous hematopoietic stem cell transplantation (autoHSCT) is a standard treatment of eligible patients suffering from Hodgkin's Lymphoma or non-Hodgkin's Lymphoma (HL, NHL). AutoHSCT allows to further improve results of the therapy. Nowadays, 99% of the procedures are performed using peripheral blood as a source of stem cells. Hence, the crucial point is to harvest adequate number of stem cells allowing hematopoietic recovery. The number of 2 × 10^6 CD34+ cells/kg is considered the minimal level in autoHSCT. There are two main mobilization strategies being used: based on G-CSF alone or in combination with chemotherapy (cyclophosphamide (CY) at dose range 1.6 g/m2 is mainly used in HL and NHL setting). However, a proportion of patients (5-40%) fail to collect the minimum number of cells required. Novel agents, like plerixafor, CXCR4 inhibitor, may enable effective CD34+ cell harvest in "poor mobilizers". Nevertheless, the optimal first-line and cost-effective protocol for mobilization of hematopoietic stem cells has not been determined so far.
Randomized trials compare chemomobilization with the use of CY + G-CSF to G-CSF alone, which had been conducted so far, did not demonstrate clear advantage of addition of CY to the growth factor. Intermediate-dose cytosine arabinoside (AraC), 1.6 g/m2 plus filgrastim, has been shown to produce very high efficacy as a first or second-line mobilization regimen in patients with lymphoid malignancies. In a retrospective comparison, this strategy was significantly more effective than CY + G-CSF. This suggest that the type of chemotherapy agent added to G-CSF may play role in mobilization efficacy and that the combination of AraC and G-CSF may be more effective than G-CSF used alone. The goal of current study is to verify this hypothesis in randomized controlled trial.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Hodgkin's lymphoma and non-Hodgkin's lymphoma patients considered eligible for autologous stem cell transplantation procedure.
- •Must not have achieved complete remission after first line of therapy or must have relapsed lymphoma.
- •Must have received at least two lines of therapy including four or more cycles.
- •Must have achieved a partial (PR) or complete remission (CR) .
- •Must be 18-65 years of age.
- •Must have World Health Organization performance status 0-
- •Time from administration or discontinuation of any chemotherapy agent must be at least four weeks.
- •Hemoglobin level > 8 g/dl, Absolute neutrophil count (ANC) > 1.5 x 10^9/L, Platelet count >100 x 10^9/L.
- •Serum creatinine < 1.5 x upper limit of normal (ULN), serum bilirubin < 1.5 ULN, serum aspartate transaminase (AST/SGOT) < 2.5 x ULN, serum alanine transaminase (ALT/SGPT) < 2.5 x ULN.
- •Negative human immunodeficiency virus (HIV) infection test.
- •Negative pregnancy test.
- •Must understand and voluntarily sign informed consent form.
排除标准
- •Failure of prior, first-line mobilization regimen.
- •Infiltration of central nervous system.
- •Bone marrow plasma cell infiltration of above 20%.
- •Administration of nitrosourea derivatives (Carmustine, Lomustine) within 4 weeks before starting study treatment.
- •Administration of growth-factor other than G-CSF Administration of G-CSF within 14 days before starting study treatment.
- •Ongoing or active infection.
- •Coexisting neoplasm, other than Hodgkin's or non-Hodgkin's lymphoma.
- •Administration of radioimmunotherapy in past.
- •Pregnant or lactating females.
- •Patients treated with use of autologous or allogenic stem cell transplantation in the past.
- •Positive human immunodeficiency virus (HIV) infection test.
研究组 & 干预措施
Cytosine arabinoside + G-CSF (filgrastim)
- Cytosine arabinoside will be administered as a 2-hour i.v. infusion at a dose of 0.4 g/m2 twice daily on days 1 and 2 (total dose 1.6 g/m2).
- G-CSF 5-10 μg/kg per day (divided into two doses every 12 hours) will be started on day 5 subcutaneously and continued until last leukapheresis.
干预措施: Cytosine arabinoside with G-CSF (filgrastim) (Drug)
G-CSF (filgrastim)
1.G-CSF at 10 μg/kg per day (divided into two doses every 12 hours) subcutaneously for up to 7 days.
干预措施: G-CSF (filgrastim) (Drug)
结局指标
主要结局
• The proportion of patients with stem cell yield at least 2 × 10^6 CD34+ cells/kg in each treatment arm.
时间窗: After up to three leukaphereses (7-20 days after starting mobilization regimen).
次要结局
- Peak level of CD34+ cells in peripheral blood (cells/μl).(7-20 days after starting mobilization regimen.)
- Total number of harvested CD34+cells/kg.(After up to three leukaphereses (7-20 days after starting mobilization regimen).)
- Number of blood transfusions needed.(1 month after transplantation.)
- Duration of hospital stay.(1 month after transplantation.)
- Time of neutrophil and platelet engraftment after autologous stem cel transplantation.(1 month after transplantation.)
- Duration of thrombocytopenia <50 x 10 ^9/L.(1 month after transplantation.)
- Number of days of antibiotics therapy.(1 month after transplantation)
- Number of leukaphereses needed to harvest target amount of stem cells.(7-20 days after starting mobilization regimen.)
- The proportion of hematologic and non-hematologic complications.(1 month after transplantation.)
- Duration of neutropenia < 0.5 x10^9/L.(1 month after transplantation.)
研究者
Sebastian Giebel
Prof., MD
Maria Sklodowska-Curie National Research Institute of Oncology