Condition category
Cancer
Date applied
16/06/2010
Date assigned
12/10/2010
Last edited
25/04/2012
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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 below 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 post–transfusion 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 measures

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

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

Stem Cell Laboratories
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

http://www.bartsandthelondon.nhs.uk/

Funders

Funder type

Charity

Funder name

Cancer Research UK (CRUK) (UK) (ref: C17401/A9616)

Alternative name(s)

CRUK

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes