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

Myelodysplastic Syndrome Clinical Trial

— REGIME  

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 Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01196715
• Other study ID #: MDS201001
• Secondary ID: 2009-017462-23CR
• Status: Not yet recruiting
• Phase: Phase 3
• First received: July 26, 2010
• Last updated: March 14, 2012
• Start date: November 2010
• Est. completion date: November 2015

Study information

• Verified date: July 2010
• Source: Barts & The London NHS Trust
• Contact: Eva Controle, BSc
• Phone: 00442078828499
• Email: e.controle[@]qmul.ac.uk
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics CommitteeUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 360
• Est. completion date: November 2015
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• Darbepoetin alpha
Aranesp 500 mcg vials once every 2 weeks.
• Filgrastim
300 mcg vials twice a week, 3-4 days apart

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.

Locations

Country	Name	City	State
United Kingdom	Birmingham Cancer Research UK Clinical Trial Unit	Birmingham
United Kingdom	CECM Institute of Cancer	London
United Kingdom	King's College Hospital Haematoloy Laboratory	London
United Kingdom	St Bartholomew's Hospital	London

Sponsors (3)

Lead Sponsor	Collaborator
Barts & The London NHS Trust	Amgen, Cancer Research UK

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No