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

Phase 3
18 Years
Open (Enrolling)
Anemia, Myelodysplastic Syndromes

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Trial Information

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


- 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

- 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

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.

Inclusion Criteria


- 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



- 18 and over

Performance status:

- ECOG 0-3

Life expectancy:

- Not specified


- See Disease Characteristics

- Platelet count greater than 30,000/mm^3 (without platelet transfusions)

- Hematocrit less than 30% (pretransfusion)


- Bilirubin less than 3 mg/dL


- BUN less than 40 mg/dL OR

- Creatinine less than 2.0 mg/dL


- No uncontrolled hypertension


- 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


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


- 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


- Not specified


- Not specified

Type of Study:


Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Principal Investigator

Kenneth B. Miller, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Beth Israel Deaconess Medical Center


United States: Federal Government

Study ID:




Start Date:

November 1997

Completion Date:

Related Keywords:

  • Anemia
  • Myelodysplastic Syndromes
  • anemia
  • refractory anemia
  • refractory anemia with ringed sideroblasts
  • refractory anemia with excess blasts
  • de novo myelodysplastic syndromes
  • previously treated myelodysplastic syndromes
  • secondary myelodysplastic syndromes
  • Anemia
  • Myelodysplastic Syndromes
  • Preleukemia



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