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Erythropoietin (EPO) and Granulocyte-Colony Stimulating Factor (G-CSF) for Low-Risk Myelodysplastic Syndromes (MDS)

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified March 2009 by St. Bartholomew's Hospital.
Recruitment status was:  Active, not recruiting
Sponsor:
ClinicalTrials.gov Identifier:
NCT00234143
First Posted: October 6, 2005
Last Update Posted: March 12, 2009
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by:
St. Bartholomew's Hospital
  Purpose

Myelodysplastic syndromes (MDS) are acquired clonal disorders of the bone marrow. The clinical consequences of MDS are bone marrow failure and a predisposition to develop acute myeloid leukaemia (AML). Patients with 'low risk MDS' have less than 10% myeloblasts in the marrow and include the World Health Organization (WHO) subtypes refractory anaemia (RA), refractory anaemia with ring sideroblasts (RARS) and refractory anaemia with excess blasts-I (RAEB-I). This group of patients has a relatively low risk of leukaemic transformation and the major clinical problem is the manifestation of bone marrow failure. Up to 80% of these patients become red cell transfusion dependent. To date, the only curative therapy is allogeneic stem cell transplantation. Unfortunately, a median age at diagnosis of > 65 years excludes this type of therapy for most patients with MDS. The aim of treatment is, therefore, supportive therapy. Long term red cell transfusion therapy carries the problems of acute transfusion reactions: iron overload, alloantibody formation, poor venous access and the risk of transfusion transmitted infection. With time, such patients require increasing frequency of transfusion and obtain decreased length of benefit from transfusion. The quality of life of such patients is significantly reduced. Alternative therapies, therefore, aimed at promoting more effective haemopoiesis and reducing the need for red cell transfusion may improve quality of life, reduce the use of expensive resources such as red cells and iron chelation, and perhaps enhance survival.

Combined darbepoetin alfa (Aranesp) plus G-CSF (Neupogen; filgrastim) in low risk MDS is better than best supportive care, with respect to haemoglobin and quality of life. The study will assess:

  • the costs of this approach
  • long-term outcomes
  • clinical/laboratory parameters allowing early cessation of therapy in patients destined not to respond

Condition Intervention Phase
Myelodysplastic Syndromes Behavioral: Darbepoetin and Filgrastim Drug: Darbepoetin Phase 2 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomised Controlled Trial of Prolonged Treatment With Darbepoetin Alpha With or Without Recombinant Human Granulocyte Colony Stimulating Factor (G-CSF) Versus Best Supportive Care in Patients With Low-Risk Myelodysplastic Syndromes

Resource links provided by NLM:


Further study details as provided by St. Bartholomew's Hospital:

Primary Outcome Measures:
  • Quality of life (Functional Assessment of Cancer Therapy-Anemia [FACT-An] and EuroQOL-5D [EQ-5D]) [ Time Frame: at week 0, 12, 24, 36 and 52 ]

Secondary Outcome Measures:
  • Overall erythroid response (major and minor) at 6 months as defined by the Cheson criteria [ Time Frame: week 24 ]
  • Overall erythroid response (major and minor) at 2 and 12 months as defined by the Cheson criteria [ Time Frame: week 8 and 52 ]
  • Incidence of disease progression (i.e. to RAEB or AML) and overall survival [ Time Frame: every 4 weeks until week 24 and at week 36 and 52 ]
  • Multivariate analysis of prospective laboratory variables in order to generate a prognostic model [ Time Frame: every 4 weeks until week 24 and at week 36 and 52 ]
  • Economic costs of managing anaemia in both arms of the study [ Time Frame: every 4 weeks until week 24 and at week 36 and 52 ]

Estimated Enrollment: 360
Study Start Date: October 2004
Arms Assigned Interventions
Active Comparator: Aranesp and Neupogen
solution for subcutaneous injection , syringe 500 mcg and 300 mcg respectively
Behavioral: Darbepoetin and Filgrastim
Aranesp and Neupogen G-CSF (Neupogen) 300 mcg s.c. twice a week, 3-4 days apart and EPO (Aranesp) 500 mcg s.c. once every 2 weeks until week 24, titrate depending of response
Active Comparator: Aranesp
solution for subcutaneous injection, 500 mcg
Drug: Darbepoetin
Aranesp EPO (Aranesp) 500 mcg s.c. once every 2 weeks until 24 weeks, titrate depending of response
No Intervention: Best supportive care
Red cell transfusion support

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 <5%
  • A haemoglobin concentration of < 10g/dl and/or red cell transfusion dependence
  • Written informed consent.

Exclusion Criteria:

  • MDS with bone marrow blasts ≥5%
  • Myelodysplastic syndrome associated with del(5q)(q31-33) syndrome
  • Chronic myelomonocytic leukaemia (monocytes >1.0x109/l)
  • therapy-related MDS
  • Splenomegaly, with spleen ≥ 5 cm from left costal margin
  • Platelets <30x109/l
  • Uncorrected haematinic deficiency
  • Age less than 18 years
  • Woman who are pregnant or lactating
  • Women of child bearing age unless using reliable contraception
  • Life expectancy < 6 months
  • Uncontrolled hypertension, previous venous thromboembolism, or uncontrolled cardiac or pulmonary disease
  • Previous adverse events to the study medications or its components
  • Patients who have had previous therapy with EPO ± G-CSF within 4 weeks of study entry
  • Patients currently receiving experimental therapy, e.g. with thalidomide, or who are participating in another clinical trial
  • Medical or psychiatric illness, which makes the patient unsuitable or unable to give, informed consent.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00234143


Locations
United Kingdom
St Bartholomew's Hospital
London, United Kingdom, EC1A 7BE
Sponsors and Collaborators
St. Bartholomew's Hospital
Investigators
Principal Investigator: Samir G Agrawal, MD, PhD St. Bartholomew's Hospital
  More Information

Responsible Party: Dr. S. Agrawal, St Bartholomew's Hospital
ClinicalTrials.gov Identifier: NCT00234143     History of Changes
Other Study ID Numbers: 04/Q1907/94
First Submitted: October 5, 2005
First Posted: October 6, 2005
Last Update Posted: March 12, 2009
Last Verified: March 2009

Keywords provided by St. Bartholomew's Hospital:
MDS
EPO
G-CSF
REGiM

Additional relevant MeSH terms:
Syndrome
Myelodysplastic Syndromes
Preleukemia
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Darbepoetin alfa
Lenograstim
Hematinics
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs