A Randomised Controlled Trial of Prolonged Treatment With Darbepoetin Alpha With or Without Recombinant Human Granulocyte Colony Stimulating Factor (G-CSF) Versus Best Supportive Care in Patients With Low-Risk Myelodysplastic Syndromes
试验速览
- 阶段
- 2 期
- 入组人数
- 360
- 试验地点
- 1
- 主要终点
- Quality of life (Functional Assessment of Cancer Therapy-Anemia [FACT-An] and EuroQOL-5D [EQ-5D])
研究概览
简要总结
Myelodysplastic syndromes (MDS) are acquired clonal disorders of the bone marrow. The clinical consequences of MDS are bone marrow failure and a predisposition to develop acute myeloid leukaemia (AML). Patients with 'low risk MDS' have less than 10% myeloblasts in the marrow and include the World Health Organization (WHO) subtypes refractory anaemia (RA), refractory anaemia with ring sideroblasts (RARS) and refractory anaemia with excess blasts-I (RAEB-I). This group of patients has a relatively low risk of leukaemic transformation and the major clinical problem is the manifestation of bone marrow failure. Up to 80% of these patients become red cell transfusion dependent. To date, the only curative therapy is allogeneic stem cell transplantation. Unfortunately, a median age at diagnosis of > 65 years excludes this type of therapy for most patients with MDS. The aim of treatment is, therefore, supportive therapy. Long term red cell transfusion therapy carries the problems of acute transfusion reactions: iron overload, alloantibody formation, poor venous access and the risk of transfusion transmitted infection. With time, such patients require increasing frequency of transfusion and obtain decreased length of benefit from transfusion. The quality of life of such patients is significantly reduced. Alternative therapies, therefore, aimed at promoting more effective haemopoiesis and reducing the need for red cell transfusion may improve quality of life, reduce the use of expensive resources such as red cells and iron chelation, and perhaps enhance survival.
Combined darbepoetin alfa (Aranesp) plus G-CSF (Neupogen; filgrastim) in low risk MDS is better than best supportive care, with respect to haemoglobin and quality of life. The study will assess:
- the costs of this approach
- long-term outcomes
- clinical/laboratory parameters allowing early cessation of therapy in patients destined not to respond
详细描述
STUDY OBJECTIVES:
Primary objectives:
- To compare the Quality of Life of Low-risk MDS patients randomised to receive prolonged treatment with EPO alone, EPO with G-CSF or best supportive care alone.
Secondary objectives:
- To compare the haemoglobin response and transfusion requirements of patients in each of these arms.
- To compare the economics costs of treating patients in each arm, in order to derive a cost:benefit analysis.
- To assess the utility of prognostic factor and predictive factor assessment, in particular against the predictive model proposed by Hellstrom-Lindberg.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A confirmed diagnosis of MDS - WHO type:
- •refractory anaemia (RA)
- •hypoplastic RA ineligible for or failed immunosuppressive therapy (ALG, cyclosporine)
- •refractory anaemia with ring sideroblasts (RARS)
- •refractory cytopenia with multilineage dysplasia
- •myelodysplastic syndrome unclassifiable
- •IPSS low or Int-1, but with BM blasts <5%
- •A haemoglobin concentration of < 10g/dl and/or red cell transfusion dependence
- •Written informed consent.
排除标准
- •MDS with bone marrow blasts ≥5%
- •Myelodysplastic syndrome associated with del(5q)(q31-33) syndrome
- •Chronic myelomonocytic leukaemia (monocytes >1.0x109/l)
- •therapy-related MDS
- •Splenomegaly, with spleen ≥ 5 cm from left costal margin
- •Platelets <30x109/l
- •Uncorrected haematinic deficiency
- •Age less than 18 years
- •Woman who are pregnant or lactating
- •Women of child bearing age unless using reliable contraception
- •Life expectancy < 6 months
- •Uncontrolled hypertension, previous venous thromboembolism, or uncontrolled cardiac or pulmonary disease
- •Previous adverse events to the study medications or its components
- •Patients who have had previous therapy with EPO ± G-CSF within 4 weeks of study entry
- •Patients currently receiving experimental therapy, e.g. with thalidomide, or who are participating in another clinical trial
- •Medical or psychiatric illness, which makes the patient unsuitable or unable to give, informed consent.
研究组 & 干预措施
Aranesp and Neupogen
solution for subcutaneous injection , syringe 500 mcg and 300 mcg respectively
干预措施: Darbepoetin and Filgrastim (Behavioral)
Aranesp
solution for subcutaneous injection, 500 mcg
干预措施: Darbepoetin (Drug)
结局指标
主要结局
Quality of life (Functional Assessment of Cancer Therapy-Anemia [FACT-An] and EuroQOL-5D [EQ-5D])
时间窗: at week 0, 12, 24, 36 and 52
次要结局
- Overall erythroid response (major and minor) at 6 months as defined by the Cheson criteria(week 24)
- Overall erythroid response (major and minor) at 2 and 12 months as defined by the Cheson criteria(week 8 and 52)
- Incidence of disease progression (i.e. to RAEB or AML) and overall survival(every 4 weeks until week 24 and at week 36 and 52)
- Multivariate analysis of prospective laboratory variables in order to generate a prognostic model(every 4 weeks until week 24 and at week 36 and 52)
- Economic costs of managing anaemia in both arms of the study(every 4 weeks until week 24 and at week 36 and 52)