Epoetin Alfa With or Without Filgrastim Compared With Blood Transfusions in Treating Patients With Myelodysplastic Syndrome - Full Text View

Sponsors and Collaborators:	Eastern Cooperative Oncology Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00003138

Purpose

RATIONALE: Epoetin alfa and colony-stimulating factors such as filgrastim stimulate the production of blood cells. It is not yet known whether epoetin alfa with or without filgrastim is more effective than standard blood transfusions in reducing the need for transfusions in patients who have anemia associated with myelodysplastic syndrome.

PURPOSE: Randomized phase III trial to compare the effectiveness of epoetin alfa with or without filgrastim with that of standard blood transfusions in reducing the need for transfusions in patients who have anemia associated with myelodysplastic syndrome.

Condition	Intervention	Phase
Anemia Myelodysplastic Syndromes Quality of Life	Biological: epoetin alfa Biological: filgrastim Procedure: quality-of-life assessment	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
Official Title:	Phase III Evaluation of EPO With or Without G-CSF Versus Supportive Therapy Alone in the Treatment of Myelodysplastic Syndromes

Resource links provided by NLM:

MedlinePlus related topics: Anemia Blood Transfusion and Donation Cancer

Drug Information available for: Erythropoietin Epoetin alfa Filgrastim

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment:	139
Study Start Date:	November 1997

Detailed Description:

OBJECTIVES:

Compare the benefit of epoetin alfa vs standard transfusion support in reducing transfusion requirements in patients with myelodysplastic syndromes.
Compare the clinical response, disease progression, and survival in patients treated with these regimens.
Compare the toxicity of these regimens in these patients.
Determine the effect of pretreatment epoetin alfa levels on the response to epoetin alfa in these patients.
Evaluate whether adding filgrastim (G-CSF) or increasing the epoetin alfa dose will reduce the transfusion requirement in patients who do not respond to epoetin alfa alone.
Assess quality of life (QOL) of these patients and determine whether either cross-sectional or longitudinal differences in patients' QOL and fatigue are correlated with the use of the growth factors.

OUTLINE: This is a randomized, controlled, multicenter, cross-over study. Patients are stratified according to morphologic subtype (refractory anemia [RA] vs RA with ringed sideroblasts vs RA with excess blasts), transfusion requirement (yes vs no), prior epoetin alfa treatment (yes vs no), and epoetin alfa level (at least 200 mU/mL vs less than 200 mU/mL). Patients are randomized to one of two treatment arms.

Arm I (standard transfusion support): Patients receive red cell and platelet transfusions for symptoms or to maintain hematocrit level of 25% or above. Patients undergo bone marrow aspirate and biopsy at 4 months and then every year until development of acute leukemia or completion of study.

Patients with progressive disease may cross over to arm II after at least 4 months on study and up to 1 year from the time of randomization. Patients who cross over receive epoetin alfa alone.

Arm II (epoetin alfa support): Patients receive epoetin alfa subcutaneously (SC) or IV daily. Patients undergo bone marrow aspirate and biopsy as in arm I. Treatment continues daily for a maximum of 1 year. Patients with stable or progressive disease at day 120 receive filgrastim (G-CSF) SC daily or 3 days a week and epoetin alfa SC daily for up to 6 months. Patients with no response to G-CSF and lower-dose epoetin alfa may proceed to a higher dose of epoetin alfa.

Quality of life is assessed at baseline, every 4 months during study, and at study completion.

Patients are followed every 4 months for 2 years, every 6 months for 3 years, and then annually for 5 years.

PROJECTED ACCRUAL: A total of 139 patients will be accrued for this study within 3.6 years.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically proven myelodysplastic syndromes
- Refractory anemia (RA)
- RA with ringed sideroblasts
- RA with excess blasts (RAEB)
RAEB patients must have a bone marrow blast count of less than 20% and less than 5% blast forms on peripheral blood
No RAEB in transformation
No chronic myelomonocytic leukemia
- Secondary myelodysplastic syndromes allowed
No splenomegaly greater than 6 cm below the left costal margin or greater than 3 times normal size

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

ECOG 0-3

Life expectancy:

Not specified

Hematopoietic:

See Disease Characteristics
Platelet count greater than 30,000/mm^3 (without platelet transfusions)
Hematocrit less than 30% (pretransfusion)

Hepatic:

Bilirubin less than 3 mg/dL

Renal:

BUN less than 40 mg/dL OR
Creatinine less than 2.0 mg/dL

Cardiovascular:

No uncontrolled hypertension

Other:

No sensitivity to E. coli-derived proteins
No sensitivity to epoetin alfa or any of its components (e.g., human albumin)
No documented iron deficiency
- If marrow iron stain is not available, the transferrin saturation must be greater than 20% or ferritin greater than 100 ng/dL
No active infection or bleeding
No other uncontrolled malignancy
Not pregnant or nursing
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Prior epoetin alfa allowed provided dosage was less than 30,000 units per week for less than 1 month duration
At least 1 month since prior epoetin alfa
At least 2 months since prior recombinant growth factor

Chemotherapy:

At least 2 months since prior chemotherapy for other malignancy or autoimmune disease

Endocrine therapy:

At least 2 weeks since prior androgens or steroids for treatment of myelodysplastic syndromes

Radiotherapy:

Not specified

Surgery:

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003138

Show 28 Study Locations

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Kenneth B. Miller, MD

Beth Israel Deaconess Medical Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Miller KB, Kim HT, Greenberg P, et al.: Phase III prospective randomized trial of EPO with or without G-CSF versus supportive therapy alone in the treatment of myelodysplastic syndromes (MDS): results of the ECOG- CLSG trial (E1996). [Abstract] Blood 104 (11): A-70, 2004.

Dewald G, Hicks G, Higgins RR, et al.: Comparison of interphase fish and metaphase cytogenetics to study myelodysplasia: an Eastern Cooperative Oncology Group (ECOG) study. [Abstract] Blood 96 (11 Pt 1): A-635, 148a, 2000.

Study ID Numbers:	CDR0000065907, ECOG-1996
Study First Received:	November 1, 1999
Last Updated:	May 9, 2009
ClinicalTrials.gov Identifier:	NCT00003138 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

quality of life
anemia
refractory anemia
refractory anemia with ringed sideroblasts

refractory anemia with excess blasts
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes

Study placed in the following topic categories:

Epoetin Alfa
Precancerous Conditions
Hematologic Diseases
Hematinics
Myelodysplastic Syndromes
Anemia
Quality of Life

Refractory Anemia
Preleukemia
Anemia, Refractory
Neoplasm Metastasis
Anemia, Refractory, with Excess of Blasts
Bone Marrow Diseases

Additional relevant MeSH terms:

Epoetin Alfa
Disease
Precancerous Conditions
Hematologic Diseases
Hematinics
Myelodysplastic Syndromes
Hematologic Agents
Anemia

Pharmacologic Actions
Preleukemia
Neoplasms
Pathologic Processes
Therapeutic Uses
Syndrome
Bone Marrow Diseases

ClinicalTrials.gov processed this record on July 02, 2009