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

Sponsor:	Eastern Cooperative Oncology Group
Collaborator:	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	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

Hide Study Locations

Locations

United States, Colorado
CCOP - Colorado Cancer Research Program, Incorporated
Denver, Colorado, United States, 80224
United States, Illinois
CCOP - Carle Cancer Center
Urbana, Illinois, United States, 61801
CCOP - Illinois Oncology Research Association
Peoria, Illinois, United States, 61602
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611
Veterans Affairs Medical Center - Lakeside Chicago
Chicago, Illinois, United States, 60611-4494
United States, Iowa
CCOP - Cedar Rapids Oncology Project
Cedar Rapids, Iowa, United States, 52403-1206
CCOP - Iowa Oncology Research Association
Des Moines, Iowa, United States, 50309-1016
United States, Louisiana
MBCCOP - LSU Health Sciences Center
New Orleans, Louisiana, United States, 70112
United States, Massachusetts
Tufts - New England Medical Center
Boston, Massachusetts, United States, 02111
United States, Michigan
CCOP - Kalamazoo
Kalamazoo, Michigan, United States, 49007-3731
CCOP - Michigan Cancer Research Consortium
Ann Arbor, Michigan, United States, 48106
West Michigan Cancer Center
Kalamazoo, Michigan, United States, 49007
United States, Minnesota
CCOP - Metro-Minnesota
Saint Louis Park, Minnesota, United States, 55416
United States, Nebraska
CCOP - Missouri Valley Cancer Consortium
Omaha, Nebraska, United States, 68106
United States, Nevada
CCOP - Southern Nevada Cancer Research Foundation
Las Vegas, Nevada, United States, 89106
United States, New Jersey
Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08903
CCOP - Northern New Jersey
Hackensack, New Jersey, United States, 07601
Veterans Affairs Medical Center - East Orange
East Orange, New Jersey, United States, 07019
United States, New York
NYU School of Medicine's Kaplan Comprehensive Cancer Center
New York, New York, United States, 10016
United States, North Dakota
CCOP - Merit Care Hospital
Fargo, North Dakota, United States, 58122
United States, Ohio
CCOP - Columbus
Columbus, Ohio, United States, 43206
MetroHealth's Cancer Care Center at MetroHealth Medical Center
Cleveland, Ohio, United States, 44109
United States, Pennsylvania
CCOP - Geisinger Clinic and Medical Center
Danville, Pennsylvania, United States, 17822-2001
United States, South Dakota
CCOP - Sioux Community Cancer Consortium
Sioux Falls, South Dakota, United States, 57104
United States, Texas
CCOP - Scott and White Hospital
Temple, Texas, United States, 76508
United States, Wisconsin
Medical College of Wisconsin Cancer Center
Milwaukee, Wisconsin, United States, 53226-3596
CCOP - St. Vincent Hospital Cancer Center, Green Bay
Green Bay, Wisconsin, United States, 54307-3453
CCOP - Marshfield Clinic Research Foundation
Marshfield, Wisconsin, United States, 54449

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:

Greenberg PL, Sun Z, Miller KB, Bennett JM, Tallman MS, Dewald G, Paietta E, van der Jagt R, Houston J, Thomas ML, Cella D, Rowe JM. Treatment of myelodysplastic syndromes patients with erythropoietin with or without granulocyte colony-stimulating factor: results of a prospective randomized phase III trial by the Eastern Cooperative Oncology Group (E1996). Blood. 2009 Jun 29; [Epub ahead of print]

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:	August 19, 2009
ClinicalTrials.gov Identifier:	NCT00003138 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

anemia
refractory anemia
refractory anemia with ringed sideroblasts
refractory anemia with excess blasts

de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes

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 November 27, 2009