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

Study Overview
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Brief Summary
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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.

Official Title
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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).

Conditions
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Myelodysplastic Syndrome

Intervention / Treatment
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* Drug: Darbepoetin alpha
* Drug: Filgrastim
* Procedure: Blood Red Cell Transfusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females aged over 18 years, (no upper age limit) ECOG performance status 0-2 Life expectancy more than 6 months 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 IPSS low or Int-1, but with BM blasts less than 5% A haemoglobin concentration of less than 10g/dl and/or red cell transfusion dependence Able to understand the implications of participation in the Trial and give written informed consent. Exclusion Criteria: MDS with bone marrow blasts greater or equal than 5% Myelodysplastic syndrome associated with del(5q)(q31-33) syndrome Chronic myelomonocytic leukaemia (monocytes greater than1.0x109/l) Therapy-related MDS Splenomegaly, with spleen greater or equal than 5 cm from left costal margin Platelets less than 30x109/l Uncorrected haematinic deficiency. Patient deplete to iron, B12 and folate according to local lab ranges Women who are pregnant or lactating. 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 Females of childbearing potential must have a negative pregnancy test prior to starting the study. Uncontrolled hypertension, previous venous thromboembolism, or uncontrolled cardiac or pulmonary disease Previous serious adverse events to the study medications or its components Patients who have had previous therapy with ESAs ± G-CSF within 4 weeks of study entry Patients currently receiving experimental therapy, e.g. with thalidomide, or who are participating in another CTIMP. Medical or psychiatric illness, which makes the patient unsuitable or unable to give informed consent. Patients with malignancy requiring active treatment (except hormonal therapy). Patients with a history of seizures

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Darbepoetin Alfa<br> | Drug: Darbepoetin alpha<br>* Aranesp 500 mcg vials once every 2 weeks.<br>* Other names: Aranesp;|
| Active Comparator: G-CSF<br> | Drug: Filgrastim<br>* 300 mcg vials twice a week, 3-4 days apart<br>* Other names: Neupogen;|
| Active Comparator: Best Supportive Care<br>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<br>* 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.<br>* Other names: Blood transfusion.;|

What is the study measuring?
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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 | weeks 0 | 
| 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 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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