Trial Information

Phase III Evaluation of EPO With or Without G-CSF Versus Supportive Therapy Alone in the Treatment of Myelodysplastic Syndromes

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.