Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Epoetin alfa With or Without Filgrastim Compared With Blood Transfusions in Treating Patients With Myelodysplastic Syndrome

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Supportive care, Treatment	Closed	18 and over	NCI	ECOG-1996 E1996, NCT00003138

Objectives

1. Compare the benefit of epoetin alfa vs standard transfusion support in reducing transfusion requirements in patients with myelodysplastic syndromes.
2. Compare the clinical response, disease progression, and survival in patients treated with these regimens.
3. Compare the toxicity of these regimens in these patients.
4. Determine the effect of pretreatment epoetin alfa levels on the response to epoetin alfa in these patients.
5. 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.
6. 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.

Entry 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

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

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/mm³ (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

Expected Enrollment

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

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.

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.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Kenneth Miller, MD, Protocol chair(Contact information may not be current)		Ph: 617-667-4599

Registry Information
Official Title		Phase III Evaluation of EPO with or without G-CSF versus Supportive Therapy Alone in the Treatment of Myelodysplastic Syndromes
Trial Start Date		1997-11-04
Registered in ClinicalTrials.gov		NCT00003138
Date Submitted to PDQ		1997-11-07
Information Last Verified		2003-06-16
NCI Grant/Contract Number		U10-CA21115

Back to Top