Myelodysplastic Syndrome
Conditions
Keywords
Quality of Life, Erythroid response, disease progression, survival, 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, Overall Survival
Brief summary
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.
Interventions
DRUGDarbepoetin alpha
Aranesp 500 mcg vials once every 2 weeks.
DRUGFilgrastim
300 mcg vials twice a week, 3-4 days apart
PROCEDUREBlood 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.
Sponsors
Cancer Research UK
Amgen
Barts & The London NHS Trust
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | weeks 0 | 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 |
| 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 | week 0 | 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 |
| 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 | week 4 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Utility of prognostic factor and predictive factor assessment | every week | To assess the utility of prognostic factor and predictive factor assessment, in particular against the predictive model proposed by Hellstrom-Lindberg. |
Countries
United Kingdom
Outcome results
None listed