Comparison Study of Standard Care Against Combination of Growth Factors Agents for Low-risk Myelodysplastic Syndromes (REGIME)

REGIME: A Randomised Controlled Trial of Prolonged Treatment With Darbepoetin Alpha, With or Without Recombinant Human Granulocyte Colony Stimulating Factor, Versus Best Supportive Care in Patients With Low-risk Myelodysplastic Syndromes (MDS).

REGIME is comparing two treatments, with Darbepoetin Alpha (DA) and Filgrastim (Granulocyte Colony Stimulating Factor, G-CSF), to the standard treatment for Myelodysplastic Syndrome (MDS).

After giving Informed Consent patients will undergo a number of tests to confirm eligibility. Once eligibility is confirmed patients will be randomly assigned to one of the three treatments group: A: Darbepoetin Alpha (DA), B: Darbepoetin Alpha and Filgrastim (DA+G-CSF), C: Blood transfusion only. Patients will be required to attend the clinic once a month for 24 weeks. After 24 weeks if a patient has reacted favorably to the treatment they may continue on the treatment regime up to 52 weeks. After week 24 all patients will be required to attend the clinic twice more, at week 36 and 52.

Patients will be followed for a further 5 years to record loss of response, transformation to Acute Myeloid Leukaemia and/or Refractory Anemia with Excess Blasts and death.

Study Overview

• Status: Completed
• Conditions: Myelodysplastic Syndrome
• Intervention / Treatment: Drug: Darbepoetin alpha; Drug: Filgrastim; Procedure: Blood Red Cell Transfusion

• Study Type: Interventional
• Enrollment (Estimated): 360
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • Birmingham, United Kingdom, B15 2TT
    • Birmingham Cancer Research UK Clinical Trial Unit
  • London, United Kingdom, EC1A 7BE
    • St Bartholomew's Hospital
  • London, United Kingdom, EC1M 6BQ
    • CECM Institute of Cancer
  • London, United Kingdom, SE5 9RS
    • King's College Hospital Haematoloy Laboratory

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Males and females aged over 18 years, (no upper age limit)
2. ECOG performance status 0-2
3. Life expectancy more than 6 months

4. A confirmed diagnosis of MDS - WHO type:

   • refractory anaemia (RA)
   • hypoplastic RA ineligible for/or failed immunosuppressive therapy (ALG, cyclosporine)
   • refractory anaemia with ring sideroblasts (RARS)
   • refractory cytopenia with multilineage dysplasia
   • myelodysplastic syndrome unclassifiable
5. IPSS low or Int-1, but with BM blasts less than 5%
6. A haemoglobin concentration of less than 10g/dl and/or red cell transfusion dependence
7. Able to understand the implications of participation in the Trial and give written informed consent.

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 than1.0x109/l)
4. Therapy-related MDS
5. Splenomegaly, with spleen greater or equal than 5 cm from left costal margin
6. Platelets less than 30x109/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 postmenopausal
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 ESAs ± G-CSF within 4 weeks of study entry
14. Patients currently receiving experimental therapy, e.g. with thalidomide, or who are participating in another CTIMP.
15. Medical or psychiatric illness, which makes the patient unsuitable or unable to give informed consent.
16. Patients with malignancy requiring active treatment (except hormonal therapy).
17. Patients with a history of seizures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Darbepoetin Alfa	Drug: Darbepoetin alpha; Aranesp 500 mcg vials once every 2 weeks.; Other Names: Aranesp
Active Comparator: G-CSF	Drug: Filgrastim; 300 mcg vials twice a week, 3-4 days apart; Other Names: Neupogen
Active Comparator: Best Supportive Care; 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 the minimum haemoglobin is never below 8.0 g/dl	Procedure: Blood Red Cell Transfusion; 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 the minimum haemoglobin is never below 8.0 g/dl or such that the patient is never excessively symptomatic, according to local transfusion guidelines/policy.; Other Names: Blood transfusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life - To compare the Quality of Life of low risk Myelodysplastic Syndrome (MDS) patients randomised to receive prolonged treatment with DA alone, DA with G-CSF or best supportive care alone	To compare the Quality of Life of low risk Myelodysplastic Syndrome (MDS) patients randomised to receive prolonged treatment with DA alone, DA with G-CSF or best supportive care alone	weeks 0
Haemoglobin response - To compare the haemoglobin response of low risk Myelodysplastic Syndrome (MDS) patients randomised to receive prolonged treatment with DA alone, DA with G-CSF or best supportive care alone	To compare the haemoglobin response of low risk Myelodysplastic Syndrome (MDS) patients randomised to receive prolonged treatment with DA alone, DA with G-CSF or best supportive care alone	week 0
Quality of Life - To compare the Quality of Life of low risk Myelodysplastic Syndrome (MDS) patients randomised to receive prolonged treatment with DA alone, DA with G-CSF or best supportive care alone	To compare the Quality of Life of low risk Myelodysplastic Syndrome (MDS) patients randomised to receive prolonged treatment with DA alone, DA with G-CSF or best supportive care alone	weeks 12
Quality of Life - To compare the Quality of Life of low risk Myelodysplastic Syndrome (MDS) patients randomised to receive prolonged treatment with DA alone, DA with G-CSF or best supportive care alone	To compare the Quality of Life of low risk Myelodysplastic Syndrome (MDS) patients randomised to receive prolonged treatment with DA alone, DA with G-CSF or best supportive care alone	weeks 24
Quality of Life - To compare the Quality of Life of low risk Myelodysplastic Syndrome (MDS) patients randomised to receive prolonged treatment with DA alone, DA with G-CSF or best supportive care alone	To compare the Quality of Life of low risk Myelodysplastic Syndrome (MDS) patients randomised to receive prolonged treatment with DA alone, DA with G-CSF or best supportive care alone	weeks 36
Quality of Life - To compare the Quality of Life of low risk Myelodysplastic Syndrome (MDS) patients randomised to receive prolonged treatment with DA alone, DA with G-CSF or best supportive care alone	To compare the Quality of Life of low risk Myelodysplastic Syndrome (MDS) patients randomised to receive prolonged treatment with DA alone, DA with G-CSF or best supportive care alone	weeks 52
Haemoglobine response - To compare the haemoglobin response of low risk Myelodysplastic Syndrome (MDS) patients randomised to receive prolonged treatment with DA alone, DA with G-CSF or best supportive care alone	To compare the haemoglobin response of low risk Myelodysplastic Syndrome (MDS) patients randomised to receive prolonged treatment with DA alone, DA with G-CSF or best supportive care alone	week 4
Haemoglobine response - To compare the haemoglobin response of low risk Myelodysplastic Syndrome (MDS) patients randomised to receive prolonged treatment with DA alone, DA with G-CSF or best supportive care alone	To compare the haemoglobin response of low risk Myelodysplastic Syndrome (MDS) patients randomised to receive prolonged treatment with DA alone, DA with G-CSF or best supportive care alone	week 8
Haemoglobine response - To compare the haemoglobin response of low risk Myelodysplastic Syndrome (MDS) patients randomised to receive prolonged treatment with DA alone, DA with G-CSF or best supportive care alone	To compare the haemoglobin response of low risk Myelodysplastic Syndrome (MDS) patients randomised to receive prolonged treatment with DA alone, DA with G-CSF or best supportive care alone	week 12
Haemoglobine response - To compare the haemoglobin response of low risk Myelodysplastic Syndrome (MDS) patients randomised to receive prolonged treatment with DA alone, DA with G-CSF or best supportive care alone	To compare the haemoglobin response of low risk Myelodysplastic Syndrome (MDS) patients randomised to receive prolonged treatment with DA alone, DA with G-CSF or best supportive care alone	week 16
Haemoglobine response - To compare the haemoglobin response of low risk Myelodysplastic Syndrome (MDS) patients randomised to receive prolonged treatment with DA alone, DA with G-CSF or best supportive care alone	To compare the haemoglobin response of low risk Myelodysplastic Syndrome (MDS) patients randomised to receive prolonged treatment with DA alone, DA with G-CSF or best supportive care alone	week 20
Haemoglobine response - To compare the haemoglobin response of low risk Myelodysplastic Syndrome (MDS) patients randomised to receive prolonged treatment with DA alone, DA with G-CSF or best supportive care alone	To compare the haemoglobin response of low risk Myelodysplastic Syndrome (MDS) patients randomised to receive prolonged treatment with DA alone, DA with G-CSF or best supportive care alone	week 24
Haemoglobine response - To compare the haemoglobin response of low risk Myelodysplastic Syndrome (MDS) patients randomised to receive prolonged treatment with DA alone, DA with G-CSF or best supportive care alone	To compare the haemoglobin response of low risk Myelodysplastic Syndrome (MDS) patients randomised to receive prolonged treatment with DA alone, DA with G-CSF or best supportive care alone	week 36
Haemoglobine response - To compare the haemoglobin response of low risk Myelodysplastic Syndrome (MDS) patients randomised to receive prolonged treatment with DA alone, DA with G-CSF or best supportive care alone	To compare the haemoglobin response of low risk Myelodysplastic Syndrome (MDS) patients randomised to receive prolonged treatment with DA alone, DA with G-CSF or best supportive care alone	week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Utility of prognostic factor and predictive factor assessment	To assess the utility of prognostic factor and predictive factor assessment, in particular against the predictive model proposed by Hellstrom-Lindberg.	every week
Utility of prognostic factor and predictive factor assessment	To assess the utility of prognostic factor and predictive factor assessment, in particular against the predictive model proposed by Hellstrom-Lindberg.	week 4
Utility of prognostic factor and predictive factor assessment	To assess the utility of prognostic factor and predictive factor assessment, in particular against the predictive model proposed by Hellstrom-Lindberg.	week 8
Utility of prognostic factor and predictive factor assessment	To assess the utility of prognostic factor and predictive factor assessment, in particular against the predictive model proposed by Hellstrom-Lindberg.	week 12
Utility of prognostic factor and predictive factor assessment	To assess the utility of prognostic factor and predictive factor assessment, in particular against the predictive model proposed by Hellstrom-Lindberg.	week 16
Utility of prognostic factor and predictive factor assessment	To assess the utility of prognostic factor and predictive factor assessment, in particular against the predictive model proposed by Hellstrom-Lindberg.	week 20
Utility of prognostic factor and predictive factor assessment	To assess the utility of prognostic factor and predictive factor assessment, in particular against the predictive model proposed by Hellstrom-Lindberg.	week 24
Utility of prognostic factor and predictive factor assessment	To assess the utility of prognostic factor and predictive factor assessment, in particular against the predictive model proposed by Hellstrom-Lindberg.	week 36
Utility of prognostic factor and predictive factor assessment	To assess the utility of prognostic factor and predictive factor assessment, in particular against the predictive model proposed by Hellstrom-Lindberg.	week 52

Collaborators and Investigators

• Sponsor: Barts & The London NHS Trust
• Collaborators: Cancer Research UK; Amgen
• Investigators: Study Director: Samir G Agrawal, MRCP FRCPath PhD, Barts and The London NHS Trust

Publications and helpful links

Helpful Links

• CR-UK funded Trial research

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2010
• Primary Completion (Actual): October 31, 2015
• Study Completion (Actual): October 31, 2015

Study Registration Dates

• First Submitted: July 26, 2010
• First Submitted That Met QC Criteria: September 6, 2010
• First Posted (Estimated): September 8, 2010

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 4, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Quality of Life; survival; disease progression; Overall Survival; Erythroid response; Overall erythroid response at 24 weeks; Quality of life at 24 weeks; Quality of life at 12, 36 and 52 weeks; Overall erythroid response at 12 and 52 weeks; Incidence of disease progression
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Hematologic Diseases; Precancerous Conditions; Bone Marrow Diseases; Syndrome; Preleukemia; Myelodysplastic Syndromes; Hematinics; Darbepoetin alfa
• Other Study ID Numbers: MDS201001; 2009-017462-23 (EudraCT Number); CRUK/08/009 (Other Grant/Funding Number: CR-UK)