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

Phase 3
Completed
Conditions
Myelodysplastic Syndrome
Interventions
Procedure: Blood Red Cell Transfusion
Registration Number
NCT01196715
Lead Sponsor
Barts & The London NHS Trust
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
360
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 & Design

Study Type
INTERVENTIONAL
Study Design
FACTORIAL
Arm && Interventions
GroupInterventionDescription
G-CSFFilgrastim-
Darbepoetin AlfaDarbepoetin alpha-
Best Supportive CareBlood Red Cell TransfusionRed 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
Primary Outcome Measures
NameTimeMethod
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 aloneweeks 52

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 aloneweek 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 aloneweek 52

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 Outcome Measures
NameTimeMethod
Utility of prognostic factor and predictive factor assessmentweek 52

To assess the utility of prognostic factor and predictive factor assessment, in particular against the predictive model proposed by Hellstrom-Lindberg.

Trial Locations

Locations (4)

Birmingham Cancer Research UK Clinical Trial Unit

🇬🇧

Birmingham, United Kingdom

St Bartholomew's Hospital

🇬🇧

London, United Kingdom

CECM Institute of Cancer

🇬🇧

London, United Kingdom

King's College Hospital Haematoloy Laboratory

🇬🇧

London, United Kingdom

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