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
DOI https://doi.org/10.1186/ISRCTN65652441
EudraCT/CTIS number 2004-002862-39
ClinicalTrials.gov number NCT00234143
Secondary identifying numbers 4658
Submission date
24/06/2010
Registration date
24/06/2010
Last edited
28/02/2019
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Ms Eva Controle
Scientific

Institute of Cancer
Rutland Place
Charterhouse Square
London
EC1M 6BQ
United Kingdom

Phone +44 20 7882 8499
Email e.controle@qmul.ac.uk

Study information

Study designMulticentre randomised interventional treatment trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)GP practice
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titleA 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)
Study acronymREGiM
Study objectivesMyelodysplastic 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(s)Brighton East Research Ethics Committee approved on the 8th November 2004 (ref: 04/Q1907/94)
Health condition(s) or problem(s) studiedTopic: National Cancer Research Network; Subtopic: Haematological Oncology; Disease: Leukaemia (acute myeloid)
InterventionThe 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 typeDrug
Pharmaceutical study type(s)
PhasePhase III
Drug / device / biological / vaccine name(s)Darbepoetin alpha (EPO), recombinant human granulocyte colony stimulating factor (G-CSF)
Primary outcome measureQuality of life at 24 weeks
Secondary outcome measures1. 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 study start date13/07/2005
Completion date11/12/2009

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participantsPlanned sample size: 1200; UK sample size: 360
Key inclusion criteria1. 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
Key exclusion criteria1. 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
Date of first enrolment13/07/2005
Date of final enrolment11/12/2009

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

Institute of Cancer
London
EC1M 6BQ
United Kingdom

Sponsor information

Barts and The London NHS Trust (UK)
Hospital/treatment centre

Queen Mary's Innovation Centre
5 Walden Street
London
E1 2EF
England
United Kingdom

Website http://www.bartsandthelondon.nhs.uk/
ROR logo "ROR" https://ror.org/00b31g692

Funders

Funder type

Charity

Cancer Research UK (CRUK) (UK) (ref: C4047)
Private sector organisation / Other non-profit organizations
Alternative name(s)
CR_UK, Cancer Research UK - London, CRUK
Location
United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Editorial Notes

28/02/2019: No publications found, verifying study status with principal investigator.
06/03/2018: No publications found, verifying study status with principal investigator.
09/02/2016: No publications found, verifying study status with principal investigator.