Contact information
Type
Scientific
Primary contact
Ms Eva Controle
ORCID ID
Contact details
Institute of Cancer
Rutland Place
Charterhouse Square
London
EC1M 6BQ
United Kingdom
+44 20 7882 8499
e.controle@qmul.ac.uk
Additional identifiers
EudraCT number
2004-002862-39
ClinicalTrials.gov number
NCT00234143
Protocol/serial number
4658
Study information
Scientific title
A randomised controlled trial of prolonged treatment with darbepoetin alpha (EPO), with or without recombinant human granulocyte colony stimulating factor (G-CSF), versus best supportive care in patients with low-risk myelodysplastic syndromes (MDS)
Acronym
REGiM
Study hypothesis
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 have a relatively low risk of leukaemic transformation and the major clinical problem is the manifestations 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 more than 65 years excludes this type of therapy for most patients with MDS. The aim of treatment is, therefore, supportive therapy (long term red cell transfusions).
In this clinical study we are investigating if treatment with an erythropoiesis stimulating agent (darbepoetin alpha) with or without G-CSF therapy can increase haemoglobin concentration and reduce/eliminate red cell transfusion in selected patients with MDS. Our primary endpoints include a measure of erythroid response and quality of life to see if treatment with darbepoetin alpha with/without G-CSF is more effective than best supportive care (long term red cell transfusions).
The trial is a multi-centre, randomised, triple arm, open-label study. We aim to open 40 sites in the UK in the first instance recruiting 360 patients in total. When the eligibility is confirmed, patients will be randomised within 42 days into a 1:1:1 ratio to either:
1. Arm A: Darbepoetin alpha and best supportive care
2. Arm B: Darbepoetin alpha with G-CSF and best supportive care
3. Arm C: Best supportive care only
Ethics approval
Brighton East Research Ethics Committee approved on the 8th November 2004 (ref: 04/Q1907/94)
Study design
Multicentre randomised interventional treatment trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
GP practices
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Topic: National Cancer Research Network; Subtopic: Haematological Oncology; Disease: Leukaemia (acute myeloid)
Intervention
The treatment schedule uses the concept of 'frontloading' to give patients the highest doses of DA at the start of therapy in order to induce a response as quickly as possible. The long-acting nature of darbepoetin alpha avoids excessive frequency of injections, but allows delivery of high doses of ESA. At week 24, if no response is achieved, the study treatment is deemed to have failed and is stopped and patients will receive 'best supportive care' only.
Arm A: Darbepoetin Alpha (Aranesp®) 500 mcg subcutaneously (s.c.) once every 2 weeks
Arm B: Aranesp® and G-CSF (Neupogen®) 300 mcg s.c. twice a week, 3 - 4 days apart
Arm C: Best supportive care; patients randomised to no growth factor treatment
Study entry: registration and one or more randomisations
Intervention type
Drug
Phase
Phase III
Drug names
Darbepoetin alpha (EPO), recombinant human granulocyte colony stimulating factor (G-CSF)
Primary outcome measure
Quality of life at 24 weeks
Secondary outcome measures
1. Quality of life at 12, 36 and 52 weeks
2. Overall erythroid response (major and minor) at 24 weeks (main analysis point) and also at 12 and 52 weeks, as defined by the International Working Group criteria
3. Incidence of disease progression
4. Overall survival
5. Economic costs of managing anaemia in each arm of the study
Overall trial start date
13/07/2005
Overall trial end date
11/12/2009
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. A confirmed diagnosis of MDS - WHO type:
1.1. Refractory anaemia (RA)
1.2. Hypoplastic RA ineligible for or failed immunosuppressive therapy (ALG, cyclosporine)
1.3. Refractory anaemia with ring sideroblasts (RARS)
1.4. Refractory cytopenia with multilineage dysplasia
1.5. Myelodysplastic syndrome unclassifiable
2. IPSS low or Int-1, but with BM blasts less than 5%
3. A haemoglobin concentration of less than 10 g/dl and/or red cell transfusion dependence
4. Written informed consent
5. Aged more than 18 years old, no upper limit, either sex
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned sample size: 1200; UK sample size: 360
Participant exclusion criteria
1. MDS with bone marrow blasts greater than or equal to 5%
2. Myelodysplastic syndrome associated with del(5q)(q31-33) syndrome
3. Chronic myelomonocytic leukaemia (monocytes greater than 1.0 x 10^9/l)
4. Therapy-related MDS
5. Splenomegaly, with spleen greater than or equal to 5 cm from left costal margin
6. Platelets less than 30 x 10^9/l
7. Uncorrected haematinic deficiency
8. Age less than 18 years
9. Woman who are pregnant or lactating
10. Women of child bearing age unless using reliable contraception
11. Life expectancy less than 6 months
12. Uncontrolled hypertension, previous venous thromboembolism, or uncontrolled cardiac or pulmonary disease
13. Previous adverse events to the study medications or its components
14. Patients who have had previous therapy with EPO ± G-CSF within 4 weeks of study entry
15. Patients currently receiving experimental therapy, e.g. with thalidomide, or who are participating in another clinical trial
16. Medical or psychiatric illness, which makes the patient unsuitable or unable to give, informed consent
Recruitment start date
13/07/2005
Recruitment end date
11/12/2009
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Institute of Cancer
London
EC1M 6BQ
United Kingdom
Sponsor information
Organisation
Barts and The London NHS Trust (UK)
Sponsor details
Queen Mary's Innovation Centre
5 Walden Street
London
E1 2EF
United Kingdom
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Charity
Funder name
Cancer Research UK (CRUK) (UK) (ref: C4047)
Alternative name(s)
CRUK
Funding Body Type
private sector organisation
Funding Body Subtype
Other non-profit organizations
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list