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

NCT01196715 | Completed Phase 3 DMC

• 3 other identifiers: MDS2010012009-017462-23CRUK/08/009
• Study Type: interventional
• Target: 360
• Locations: 1 country
• Sites: 4

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.

Conditions

Myelodysplastic Syndrome

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

Outcome Measures

Primary Outcomes (14)

• 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

  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

• 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

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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 Outcomes (9)

• Utility of prognostic factor and predictive factor assessment

  every week

• Utility of prognostic factor and predictive factor assessment

  week 4

• Utility of prognostic factor and predictive factor assessment

  week 8

• Utility of prognostic factor and predictive factor assessment

  week 12

• Utility of prognostic factor and predictive factor assessment

  week 16

Study Arms (3)

Darbepoetin Alfa

ACTIVE COMPARATOR

Drug: Darbepoetin alpha

G-CSF

ACTIVE COMPARATOR

Drug: Filgrastim

Best Supportive Care

ACTIVE COMPARATOR

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

Interventions

Darbepoetin alpha DRUG

Aranesp 500 mcg vials once every 2 weeks.

Also known as: Aranesp

Darbepoetin Alfa

Filgrastim DRUG

300 mcg vials twice a week, 3-4 days apart

Also known as: Neupogen

G-CSF

Blood Red Cell Transfusion PROCEDURE

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.

Also known as: Blood transfusion.

Best Supportive Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Barts & The London NHS Trust: lead
• Cancer Research UK: collaborator
• Amgen: collaborator

Study Sites (4)

Birmingham Cancer Research UK Clinical Trial Unit

Birmingham, B15 2TT, United Kingdom

Location

St Bartholomew's Hospital

London, EC1A 7BE, United Kingdom

Location

CECM Institute of Cancer

London, EC1M 6BQ, United Kingdom

Location

King's College Hospital Haematoloy Laboratory

London, SE5 9RS, United Kingdom

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Disease Progression

Interventions

Darbepoetin alfa; Filgrastim; Erythrocyte Transfusion; Blood Transfusion

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Erythropoietin; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Proteins; Amino Acids, Peptides, and Proteins; Granulocyte Colony-Stimulating Factor; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Blood Component Transfusion; Biological Therapy; Therapeutics

Study Officials

• Samir G Agrawal, MRCP FRCPath PhD

  Barts and The London NHS Trust

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2010
• First Posted: September 8, 2010
• Study Start: November 1, 2010
• Primary Completion: October 31, 2015
• Study Completion: October 31, 2015
• Last Updated: February 6, 2025

Record last verified: 2025-02

Locations

GB (4)