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

NCT00234143 | Unknown Phase 2 DMC

• 1 other identifier: 04/Q1907/94
• Study Type: interventional
• Target: 360
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Myelodysplastic Syndromes

Keywords

MDS; EPO; G-CSF; REGiM

Outcome Measures

Primary Outcomes (1)

• Quality of life (Functional Assessment of Cancer Therapy-Anemia [FACT-An] and EuroQOL-5D [EQ-5D])

  at week 0, 12, 24, 36 and 52

Secondary Outcomes (5)

• 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

Study Arms (3)

Aranesp and Neupogen

ACTIVE COMPARATOR

solution for subcutaneous injection , syringe 500 mcg and 300 mcg respectively

Behavioral: Darbepoetin and Filgrastim

Aranesp

ACTIVE COMPARATOR

solution for subcutaneous injection, 500 mcg

Drug: Darbepoetin

Best supportive care

NO INTERVENTION

Red cell transfusion support

Interventions

Darbepoetin and Filgrastim BEHAVIORAL

Aranesp and Neupogen G-CSF (Neupogen) 300 mcg s.c. twice a week, 3-4 days apart and EPO (Aranesp) 500 mcg s.c. once every 2 weeks until week 24, titrate depending of response

Aranesp and Neupogen

Darbepoetin DRUG

Aranesp EPO (Aranesp) 500 mcg s.c. once every 2 weeks until 24 weeks, titrate depending of response

Aranesp

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• St. Bartholomew's Hospital: lead

Study Sites (1)

St Bartholomew's Hospital

London, EC1A 7BE, United Kingdom

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Darbepoetin alfa; Filgrastim

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Erythropoietin; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Proteins; Amino Acids, Peptides, and Proteins; Granulocyte Colony-Stimulating Factor; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors

Study Officials

• Samir G Agrawal, MD, PhD

  St. Bartholomew's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 5, 2005
• First Posted: October 6, 2005
• Study Start: October 1, 2004
• Last Updated: March 12, 2009

Record last verified: 2009-03

Locations

GB (1)