Contact information
Type
Scientific
Primary contact
Dr Samir Agrawal
ORCID ID
Contact details
Stem Cell Laboratories
St Bartholomew's Hospital
West Smithfield
London
EC1A 7BE
United Kingdom
-
s.g.agrawal@qmul.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
NCT01196715
Protocol/serial number
version 1.1 dated 21 May 2010
Study information
Scientific title
REGiME Trial: A randomised controlled trial of prolonged treatment with darbepoetin alpha (DA) with/without recombinant human granulocyte colony stimulating factor (G-CSF), versus best supportive care in patients with low-risk myelodysplastic syndromes
Acronym
REGiME
Study hypothesis
To compare the haemoglobin response and quality of life of low risk myelodysplastic syndrome (MDS) patients randomised to receive prolonged treatment with darbepoetin alpha (DA) alone, DA with recombinant human granulocyte colony stimulating factor (G-CSF) or best supportive care alone.
Ethics approval
Not provided at time of registration
Study design
Randomised controlled triple-arm study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Low-risk myelodysplastic syndrome
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. Response assessment will follow IWG criteria.
Arm A:
Darbepoetin alpha (Aranesp®) and best supportive care if applicable:
1. Aranesp® 500 µg subcutaneous (s.c.) once every 2 weeks:
1.1. If a rapid response is obtained (haemoglobin [Hb] increase greater than or equal to 2 g/dl in any 4 week period), titrate down the dose frequency of Aranesp®
1.2. If major response, titrate Aranesp® to lowest dose frequency that maintains the response
2. At 24 weeks:
2.1. If no response, stop Aranesp® and give supportive therapy only
2.2. If minor response, continue Aranesp® 500 µg once every 2 weeks s.c.
2.3. If major response, titrate Aranesp® to lowest dose frequency that maintains the response
3. If patients present symptoms, they will receive red cell transfusion support to achieve a predicted posttransfusion haemoglobin of 11.0 to 12.0 g/dl at a quantity and frequency such that:
3.1. The minimum haemoglobin is never below 8.0 g/dl, or
3.2. The patient is never excessively symptomatic, according to local transfusion guidelines/policy
Arm B:
Darbepoetin alpha (Aranesp®) and recombinant human granulocyte colony stimulating factor (G-CSF) and best supportive care if applicable:
1. G-CSF (Neupogen®) 300 µg s.c. twice a week, 3 - 4 days apart
2. Aranesp® 500 µg s.c. once every 2 weeks:
2.1. If a rapid response is obtained (Hb increase greater than or equal to 2 g/dl in any 4 week period), titrate down the dose frequency of Aranesp®
2.2. If major response, titrate Aranesp® and G-CSF to lowest dose frequency that maintains the response
3. At 24 weeks:
3.1. If no response, stop Aranesp® and G-CSF and give supportive therapy only
3.2. If minor response, continue Aranesp® 500 µg every 2 weeks s.c. and G-CSF 300 µg s.c. twice a week, 3 - 4 days apart
3.3. If major response, titrate Aranesp® and G-CSF to lowest dose frequency that maintains the response
4. If patients present symptoms, they will receive red cell transfusion support to achieve a predicted post-transfusion haemoglobin of 11.0 to 12.0 g/dl at a quantity and frequency such that:
4.1. The minimum haemoglobin is never below 8.0 g/dl, or
4.2. The patient is never excessively symptomatic, according to local transfusion guidelines/policy
Arm C:
Best supportive care only:
Patients randomised to no growth factor treatment will receive best supportive care only, which is defined as red cell transfusion support to achieve a predicted post-transfusion haemoglobin of 11.0 to 12.0 g/dl at a quantity and frequency such that;
1. The minimum haemoglobin is never below 8.0 g/dl, or
2. The patient is never excessively symptomatic, according to local transfusion guidelines/policy
Intervention type
Drug
Phase
Phase III
Drug names
Darbepoetin alpha, recombinant human granulocyte colony stimulating factor
Primary outcome measure
1. Quality of life, measured at weeks 0, 12, 24, 36 and 52
2. Haemoglobine response, measured every week until 24 weeks and then at weeks 36 and 52
Secondary outcome measures
1. Economic costs measured at baseline
2. Utility of prognostic factor and predictive factor assessment, measured weekly
Overall trial start date
01/11/2010
Overall trial end date
31/10/2015
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Males and females aged over 18 years (no upper age limit)
2. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2
3. Life expectancy more than 6 months
4. A confirmed diagnosis of MDS - World Health Organization (WHO) type:
4.1. Refractory anaemia (RA)
4.2. Hypoplastic RA ineligible for or failed immunosuppressive therapy (antilymphocyte globulin [ALG], cyclosporine)
4.3. Refractory anaemia with ring sideroblasts (RARS)
4.4. Refractory cytopenia with multilineage dysplasia
4.5. Myelodysplastic syndrome unclassifiable
5. International Prognostic Scoring System (IPSS) low or Int-1, but with bone marrow (BM) blasts less than 5%
6. A haemoglobin concentration of less than 10 g/dl and/or red cell transfusion dependence
7. Able to understand the implications of participation in the trial and give written informed consent
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
360
Participant exclusion criteria
1. MDS with bone marrow blasts greater or equal than 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 or equal than 5 cm from left costal margin
6. Platelets less than 30 x 10^9/l
7. Uncorrected haematinic deficiency. Patient deplete to iron, B12 and folate according to local lab ranges.
8. Women who are pregnant or lactating
9. Females of childbearing potential and all males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) for the duration of the study and for up to 3 months after the last dose of study medication. Note: Subjects are not considered of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are post-menopausal.
10. Females of childbearing potential must have a negative pregnancy test prior to starting the study
11. Uncontrolled hypertension, previous venous thromboembolism, or uncontrolled cardiac or pulmonary disease
12. Previous serious adverse events to the study medications or its components
13. Patients who have had previous therapy with erythropoiesis-stimulating agents (ESAs) with/without G-CSF within 4 weeks of study entry
14. Patients currently receiving experimental therapy, e.g. with thalidomide, or who are participating in another clinical trial of investigational medicinal product (CTIMP)
15. Medical or psychiatric illness, which makes the patient unsuitable or unable to give informed consent
Recruitment start date
01/11/2010
Recruitment end date
31/10/2015
Locations
Countries of recruitment
United Kingdom
Trial participating centre
St Bartholomew's Hospital
London
EC1A 7BE
United Kingdom
Sponsor information
Organisation
Barts and The London NHS Trust (UK)
Sponsor details
Queen Mary's Innovation Centre
Lower Ground Floor
5 Walden Street
London
E1 2AN
United Kingdom
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Charity
Funder name
Cancer Research UK (CRUK) (UK) (ref: C17401/A9616)
Alternative name(s)
Funding Body Type
unknown
Funding Body Subtype
Location
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