A Randomized Study of Peripheral Blood Progenitor Cell Priming Comparing a Combination of r-metHuSCF and Filgrastim or Chemotherapy and Filgrastim on Mobilization and Engraftment in Patients With Relapsed or Refractory Lymphomas
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 32
- 试验地点
- 8
- 主要终点
- Safety and Toxicity was assessed by morbidity, including unexpected adverse events associated with the priming and the transplantation phases during study, and measured and graded by CTC criteria.
研究概览
简要总结
Clinical Hypothesis:
It is expected that by removing chemotherapy and adding ancestim to the mobilization scheme in most of the subjects sufficient PBPC will be harvested with a minimum of toxicity and side effects.
详细描述
Autologous stem cell transplantation is used to support high dose chemotherapy in haematological malignancies.1-2 Peripheral blood progenitor cells (PBPC) have replaced bone marrow cells as the preferred source for transplantation due to faster blood cell recovery.3-4 One variable of major impact for posttransplant care is the number of PBPC harvested.5-8 Therefore, several clinical studies have aimed to identify priming regimens that improve progenitor and stem cell mobilizations and collections without increased toxicity. Frequently, Filgrastim (r-met HuG-CSF) is administrated alone; however, Filgrastim combined with chemotherapy has proven more effective in context of CD34+ cell numbers harvested9-11 and this combination is considered the gold standard for priming and stem cell mobilization in relapsed malignant lymphoma.
Stem cell factor (SCF) is a glycoprotein growth factor that acts on haematopoietic blood cell progenitors.12 Whereas SCF alone exerts little colony-stimulating activity on normal human bone marrow cells in vitro, combination of SCF with other recombinant haematopoietic cytokines results in a synergistic increase in numbers of colonies.13 In vivo, the addition of SCF to G-CSF (Filgrastim) synergistically increases PBPC mobilization compared to Filgrastim alone.14-17 Several clinical trials have reported the ability of the combination of SCF with Filgrastim to mobilize PBPC in patients with lymphoma, multiple myeloma, breast and ovarian cancers even in heavily pretreated patients.18-26 Priming using chemotherapy is toxic and costly11 and new priming procedures need to be established, which is the background for this randomized pilot study. The hypothesis is that elimination of chemotherapy from the priming regimen may decrease the overall toxicity and the ability to collect a sufficient autograft which, however, may be circumvented by adding r-metHuSCF (Ancestim) to the priming regimen. The aim of this randomized phase II trial was to evaluate safety, toxicity and efficacy of growth factors in lymphoma patients considered candidates for high dose chemotherapy.
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
- Triple (Participant, Care Provider, Investigator)
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
- •Subjects with Hodgkin's disease and non-Hodgkin lymphomas (Real classification)
- •in relapse
- •refractory to initial chemotherapy
- •with partial response after initial therapy
- •Age > 18 years and < 65 years
- •ECOG performance status 0, 1 or 2
- •Life expectancy of > 6 months with treatment
- •ANC > or equal to 1.5 x 109/L, Platelets > or equal to 100 x 109/L
- •Serum creatinine < or equal to 150 µmol/L, bilirubin, aspartate aminotransferase (ASAT), and alanine aminotransferase (ALAT) less than twice the upper limit defined at the investigating laboratory
- •Prior to mobilization chemotherapy subject has given written informed consent, personally dated
排除标准
- •Prior DexaBEAM or miniBEAM therapy and prior bone marrow or PBPC transplant
- •Any history of seasonal or recurrent asthma within the preceding 10 years.
- •Any history of anaphylactic / anaphylactoid-type event manifested by disseminated urticaria, laryngeal oedema, and / or bronchospasm (example, food, insect bites, etc.). Subjects with drug allergies, manifested solely by rash and / or urticaria, are not excluded
- •Any history of angioedema or recurrent urticaria
- •Clinical or microbiological evidence of infection at the date of enrollment.
- •Subjects with a concurrent malignancy
- •Significant non-malignant disease including documented HIV infection, uncontrolled hypertension, unstable angina, congestive heart failure, poorly controlled diabetes, coronary angioplasty within six months, myocardial infarction within the last six months, or uncontrolled atrial or ventricular cardiac arrhythmias
- •Pregnant or breast feeding subjects or those of child-bearing potential who are not using adequate contraceptive precautions
- •Concurrent enrollment on any other protocol using an investigational drug
- •Haematopoietic growth factors administered within one week of study entry
- •Subjects with a psychiatric, addictive or any disorder which compromises ability to give truly informed consent for participation in this study
- •Known sensitivity to E. coli derived products
- •Concurrent use of beta adrenergic blocking agents
研究组 & 干预措施
Cyclophosphamide and Filgrastim
Patients were randomized in a 1:1 ratio to either chemotherapy combined with 10 µg/kg/d Filgrastim (control arm B), administered by subcutaneous injection for 14 days, or the combination of 10 µg/kg/d Filgrastim and SCF administered subcutaneously at a dose of 20 µg/kg/d (experimental arm A) for 8 days. Different injection sites were used for each cytokine.
干预措施: Chemotherapy plus Filgrastim (Drug)
r-metHuSCF and Filgrastim
Patients were randomized in a 1:1 ratio to either chemotherapy combined with 10 µg/kg/d Filgrastim (control arm B), administered by subcutaneous injection for 14 days, or the combination of 10 µg/kg/d Filgrastim and SCF administered subcutaneously at a dose of 20 µg/kg/d (experimental arm A) for 8 days. Different injection sites were used for each cytokine.
干预措施: r-metHuSCF and Filgrastim (Drug)
r-metHuSCF and Filgrastim
Patients were randomized in a 1:1 ratio to either chemotherapy combined with 10 µg/kg/d Filgrastim (control arm B), administered by subcutaneous injection for 14 days, or the combination of 10 µg/kg/d Filgrastim and SCF administered subcutaneously at a dose of 20 µg/kg/d (experimental arm A) for 8 days. Different injection sites were used for each cytokine.
干预措施: Chemotherapy plus Filgrastim (Drug)
Cyclophosphamide and Filgrastim
Patients were randomized in a 1:1 ratio to either chemotherapy combined with 10 µg/kg/d Filgrastim (control arm B), administered by subcutaneous injection for 14 days, or the combination of 10 µg/kg/d Filgrastim and SCF administered subcutaneously at a dose of 20 µg/kg/d (experimental arm A) for 8 days. Different injection sites were used for each cytokine.
干预措施: r-metHuSCF and Filgrastim (Drug)
结局指标
主要结局
Safety and Toxicity was assessed by morbidity, including unexpected adverse events associated with the priming and the transplantation phases during study, and measured and graded by CTC criteria.
时间窗: From inclusion to 1 months post transplantation
次要结局
- To compare the time dependent level of blood circulating and harvested haematopoietic stem cells and progenitors (PBSC) in patients treated with either a combination of r-metHuSCF and Filgrastim, or conventional chemotherapy plus Filgrastim.(From inclusion to 1 months post transplantation)