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11 February 2012
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| [ Print-friendly version ] |
| REGiM: Prolonged treatment with darbepoetin alpha (EPO), with/without recombinant human granulocyte colony stimulating factor (G-CSF), versus best supportive care in patients with low-risk myelodysplastic syndromes (MDS) |
| ISRCTN | ISRCTN65652441 |
| ClinicalTrials.gov identifier | NCT00234143 |
| Public title | REGiM: Prolonged treatment with darbepoetin alpha (EPO), with/without recombinant human granulocyte colony stimulating factor (G-CSF), versus best supportive care in patients with low-risk myelodysplastic syndromes (MDS) |
| 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 |
| Serial number at source | 4658 |
| 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 |
| Lay summary | Not provided at time of registration |
| Ethics approval | Brighton East Research Ethics Committee approved on the 8th November 2004 (ref: 04/Q1907/94) |
| Study design | Multicentre randomised interventional treatment trial |
| Countries of recruitment | United Kingdom |
| Disease/condition/study domain | Topic: National Cancer Research Network; Subtopic: Haematological Oncology; Disease: Leukaemia (acute myeloid) |
| Participants - 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 |
| Participants - 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 |
| Anticipated start date | 13/07/2005 |
| Anticipated end date | 11/12/2009 |
| Status of trial | Completed |
| Patient information material | Not available in web format, please use the contact details below to request a patient information sheet |
| Target number of participants | Planned sample size: 1200; UK sample size: 360 |
| Interventions |
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 |
| Primary outcome measure(s) | Quality of life at 24 weeks |
| Secondary outcome measure(s) |
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 |
| Sources of funding | Cancer Research UK (CRUK) (UK) (ref: C4047) |
| Trial website | |
| Publications | |
| Contact name | Ms Eva Controle |
| Address |
Institute of Cancer
Rutland Place Charterhouse Square |
| City/town | London |
| Zip/Postcode | EC1M 6BQ |
| Country | United Kingdom |
| e.controle@qmul.ac.uk | |
| Sponsor | Barts and The London NHS Trust (UK) |
| Address |
Queen Mary's Innovation Centre
5 Walden Street |
| City/town | London |
| Zip/Postcode | E1 2EF |
| Country | United Kingdom |
| Sponsor website: | http://www.bartsandthelondon.nhs.uk/ |
| Date applied | 24/06/2010 |
| Last edited | 30/11/2011 |
| Date ISRCTN assigned | 24/06/2010 |
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