Erythropoietin (EPO) and Granulocyte-Colony Stimulating Factor (G-CSF) for Low-Risk Myelodysplastic Syndromes (MDS)

• Status: Unknown status
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: St. Bartholomew's Hospital
• Treatments: Darbepoetin alfa; Lenograstim

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.