Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Supportive care, Treatment	Closed	18 and over	NCI, Other	CDR0000065907 ECOG-1996, NCT00003138

Trial Description

Summary

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.

Further Study Information

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 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

Trial Contact Information

Trial Lead Organizations/Sponsors

Eastern Cooperative Oncology Group

Kenneth B. Miller

Study Chair

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00003138
Information obtained from ClinicalTrials.gov on March 18, 2010

Back to Top