Clinical Trials /

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

NCT01196715

Description:

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.

Related Conditions:
  • Myelodysplastic Syndrome, Unclassifiable
  • Refractory Anemia
  • Refractory Cytopenia with Multilineage Dysplasia
  • Refractory anemia with ring sideroblasts
Recruiting Status:

Unknown status

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title:Comparison Study of Standard Care Against Combination of Growth Factors Agents for Low-risk Myelodysplastic Syndromes
  • Official Title: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).

Clinical Trial IDs

  • ORG STUDY ID: MDS201001
  • SECONDARY ID: 2009-017462-23
  • SECONDARY ID: CRUK/08/009
  • NCT ID: NCT01196715

Trial Conditions

  • Myelodysplastic Syndrome

Trial Interventions

DrugSynonymsArms
Darbepoetin alphaAranespDarbepoetin Alfa
FilgrastimNeupogenG-CSF

Trial Purpose

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.

Detailed Description

Trial Arms

NameTypeDescriptionInterventions
Darbepoetin AlfaActive Comparator
  • Darbepoetin alpha
    G-CSFActive Comparator
      • Filgrastim
      Best Supportive CareActive ComparatorRed 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

        Eligibility Criteria

        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

        Maximum Eligible Age:N/A
        Minimum Eligible Age:18 Years
        Eligible Gender:Both
        Healthy Volunteers:No

        Primary Outcome Measures

        Measure:Quality of Life
        Time Frame:weeks 0
        Safety Issue:No
        Description: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

        Secondary Outcome Measures

        Measure:Utility of prognostic factor and predictive factor assessment
        Time Frame:every week
        Safety Issue:No
        Description:To assess the utility of prognostic factor and predictive factor assessment, in particular against the predictive model proposed by Hellstrom-Lindberg.
        Measure:Utility of prognostic factor and predictive factor assessment
        Time Frame:week 4
        Safety Issue:No
        Description:To assess the utility of prognostic factor and predictive factor assessment, in particular against the predictive model proposed by Hellstrom-Lindberg.
        Measure:Utility of prognostic factor and predictive factor assessment
        Time Frame:week 8
        Safety Issue:No
        Description:To assess the utility of prognostic factor and predictive factor assessment, in particular against the predictive model proposed by Hellstrom-Lindberg.
        Measure:Utility of prognostic factor and predictive factor assessment
        Time Frame:week 12
        Safety Issue:No
        Description:To assess the utility of prognostic factor and predictive factor assessment, in particular against the predictive model proposed by Hellstrom-Lindberg.
        Measure:Utility of prognostic factor and predictive factor assessment
        Time Frame:week 16
        Safety Issue:No
        Description:To assess the utility of prognostic factor and predictive factor assessment, in particular against the predictive model proposed by Hellstrom-Lindberg.
        Measure:Utility of prognostic factor and predictive factor assessment
        Time Frame:week 20
        Safety Issue:No
        Description:To assess the utility of prognostic factor and predictive factor assessment, in particular against the predictive model proposed by Hellstrom-Lindberg.
        Measure:Utility of prognostic factor and predictive factor assessment
        Time Frame:week 24
        Safety Issue:No
        Description:To assess the utility of prognostic factor and predictive factor assessment, in particular against the predictive model proposed by Hellstrom-Lindberg.
        Measure:Utility of prognostic factor and predictive factor assessment
        Time Frame:week 36
        Safety Issue:No
        Description:To assess the utility of prognostic factor and predictive factor assessment, in particular against the predictive model proposed by Hellstrom-Lindberg.
        Measure:Utility of prognostic factor and predictive factor assessment
        Time Frame:week 52
        Safety Issue:No
        Description:To assess the utility of prognostic factor and predictive factor assessment, in particular against the predictive model proposed by Hellstrom-Lindberg.

        Trial 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