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 standardblood transfusions in reducing the need for transfusions in patients who have anemia associated with myelodysplastic syndrome.

PURPOSE: Randomizedphase 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	Treatment or Intervention	Phase
Anemia Myelodysplastic Syndromes Quality of Life	Drug: epoetin alfa  Drug: filgrastim  Procedure: biological response modifier therapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: hematologic toxicity attenuation  Procedure: quality-of-life assessment  Procedure: supportive care/therapy	Phase III

Further Study Details: 

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.
• 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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

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

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

Study chairs or principal investigators

Kenneth B. Miller, MD,  Study Chair,  Beth Israel Deaconess Medical Center   

Study ID Numbers:  CDR0000065907; ECOG-1996
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003138
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08