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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified July 2010 by Barts & The London NHS Trust
Sponsor:
Collaborators:
Cancer Research UK
Amgen
Information provided by:
Barts & The London NHS Trust
ClinicalTrials.gov Identifier:
NCT01196715
First received: July 26, 2010
Last updated: March 14, 2012
Last verified: July 2010
  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.


Condition Intervention Phase
Myelodysplastic Syndrome
Drug: Darbepoetin alpha
Drug: Filgrastim
Procedure: Blood Red Cell Transfusion
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
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).

Resource links provided by NLM:


Further study details as provided by Barts & The London NHS Trust:

Primary Outcome Measures:
  • Quality of Life [ Time Frame: weeks 0 ] [ Designated as safety issue: No ]
    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

  • Haemoglobine response [ Time Frame: week 0 ] [ Designated as safety issue: No ]
    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

  • Quality of Life [ Time Frame: weeks 12 ] [ Designated as safety issue: No ]
    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

  • Quality of Life [ Time Frame: weeks 24 ] [ Designated as safety issue: No ]
    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

  • Quality of Life [ Time Frame: weeks 36 ] [ Designated as safety issue: No ]
    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

  • Quality of Life [ Time Frame: weeks 52 ] [ Designated as safety issue: No ]
    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

  • Haemoglobine response [ Time Frame: week 4 ] [ Designated as safety issue: No ]
    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 [ Time Frame: week 8 ] [ Designated as safety issue: No ]
    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 [ Time Frame: week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: week 16 ] [ Designated as safety issue: No ]
    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 [ Time Frame: week 20 ] [ Designated as safety issue: No ]
    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 [ Time Frame: week 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: week 36 ] [ Designated as safety issue: No ]
    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 [ Time Frame: week 52 ] [ Designated as safety issue: No ]
    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:
  • Utility of prognostic factor and predictive factor assessment [ Time Frame: every week ] [ Designated as safety issue: No ]
    To assess the utility of prognostic factor and predictive factor assessment, in particular against the predictive model proposed by Hellstrom-Lindberg.

  • Utility of prognostic factor and predictive factor assessment [ Time Frame: week 4 ] [ Designated as safety issue: No ]
    To assess the utility of prognostic factor and predictive factor assessment, in particular against the predictive model proposed by Hellstrom-Lindberg.

  • Utility of prognostic factor and predictive factor assessment [ Time Frame: week 8 ] [ Designated as safety issue: No ]
    To assess the utility of prognostic factor and predictive factor assessment, in particular against the predictive model proposed by Hellstrom-Lindberg.

  • Utility of prognostic factor and predictive factor assessment [ Time Frame: week 12 ] [ Designated as safety issue: No ]
    To assess the utility of prognostic factor and predictive factor assessment, in particular against the predictive model proposed by Hellstrom-Lindberg.

  • Utility of prognostic factor and predictive factor assessment [ Time Frame: week 16 ] [ Designated as safety issue: No ]
    To assess the utility of prognostic factor and predictive factor assessment, in particular against the predictive model proposed by Hellstrom-Lindberg.

  • Utility of prognostic factor and predictive factor assessment [ Time Frame: week 20 ] [ Designated as safety issue: No ]
    To assess the utility of prognostic factor and predictive factor assessment, in particular against the predictive model proposed by Hellstrom-Lindberg.

  • Utility of prognostic factor and predictive factor assessment [ Time Frame: week 24 ] [ Designated as safety issue: No ]
    To assess the utility of prognostic factor and predictive factor assessment, in particular against the predictive model proposed by Hellstrom-Lindberg.

  • Utility of prognostic factor and predictive factor assessment [ Time Frame: week 36 ] [ Designated as safety issue: No ]
    To assess the utility of prognostic factor and predictive factor assessment, in particular against the predictive model proposed by Hellstrom-Lindberg.

  • Utility of prognostic factor and predictive factor assessment [ Time Frame: week 52 ] [ Designated as safety issue: No ]
    To assess the utility of prognostic factor and predictive factor assessment, in particular against the predictive model proposed by Hellstrom-Lindberg.


Estimated Enrollment: 360
Study Start Date: November 2010
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Darbepoetin Alfa Drug: Darbepoetin alpha
Aranesp 500 mcg vials once every 2 weeks.
Other Name: Aranesp
Active Comparator: G-CSF Drug: Filgrastim
300 mcg vials twice a week, 3-4 days apart
Other Name: 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 Name: Blood transfusion.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01196715

Contacts
Contact: Eva Controle, BSc 00442078828499 ext 8499 e.controle@qmul.ac.uk
Contact: REGIME Coordinators 00442078828499 ext 8499 regime@qmcr.qmul.qc.uk

Locations
United Kingdom
Birmingham Cancer Research UK Clinical Trial Unit Not yet recruiting
Birmingham, United Kingdom, B15 2TT
Contact: Data Manager    00441214159132    regime@trials.bham.ac.uk   
CECM Institute of Cancer Not yet recruiting
London, United Kingdom, EC1M 6BQ
Contact: Eva Controle, BSc    00442078828499    e.controle@qmul.ac.uk   
Contact: REGIME Coordinators    00442078828499    regime@qmcr.qmul.ac.uk   
St Bartholomew's Hospital Not yet recruiting
London, United Kingdom, EC1A 7BE
Contact: Sarah Knight       sarah.knight@bartsandthelondon.nhs.uk   
Principal Investigator: Samir G Agrawal         
King's College Hospital Haematoloy Laboratory Not yet recruiting
London, United Kingdom, SE5 9RS
Contact: Aloysius Ho    00442077374000 ext 4153      
Sponsors and Collaborators
Barts & The London NHS Trust
Cancer Research UK
Amgen
Investigators
Study Director: Samir G Agrawal, MRCP FRCPath PhD Barts and The London NHS Trust
  More Information

No publications provided

Responsible Party: Dr Samir G. Agrawal, Barts & The London NHS Trust
ClinicalTrials.gov Identifier: NCT01196715     History of Changes
Other Study ID Numbers: MDS201001, 2009-017462-23, CRUK/08/009
Study First Received: July 26, 2010
Last Updated: March 14, 2012
Health Authority: United Kingdom: Research Ethics Committee
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Barts & The London NHS Trust:
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

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Lenograstim
Darbepoetin alfa
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Hematinics
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014