A Phase III, Randomized Study of the Effects of Parenteral Iron, Oral Iron, or No Iron Supplementation on the Erythropoietic Response to Darbepoetin Alfa for Cancer Patients With Chemotherapy-Associated Anemia
* To compare the effects of IV iron, oral iron, or placebo in combination with darbepoetin
alfa on the hematopoietic response rate, defined as a hemoglobin increment of ≥ 2.0 g/dL
from baseline or achievement of hemoglobin of ≥ 11 g/dL in the absence of red blood cell
transfusions (RBC) in the preceding 28 days of the treatment period, in cancer patients with
- To compare the effects of these regimens on the mean hemoglobin increment from baseline
to weeks 7 and 16 in these patients.
- To compare the effects of these regimens on the percentage of patients maintaining an
average hemoglobin level within the American Society of Hematology/American Society of
Clinical Oncology (ASH/ASCO)and National Comprehensive Cancer Network(NCCN)
guideline-based target hemoglobin range (11-13 g/dL), once achieving a hemoglobin of ≥
11 g/dL from week 1 to week 16 in the absence of RBC transfusions in the preceding 28
days of the treatment period.
- To compare the effects of intravenously (IV) iron, oral iron, or placebo on the
response to darbepoetin alfa, in terms of time to achieving hemoglobin levels of ≥
- To compare the effects of these regimens on the percentage of patients who require RBC
transfusions and the total transfusion needs.
- To compare the effects of these regimens on the change in hemoglobin week by week.
- To compare the effects of these regimens on quality-of-life changes from baseline to
weeks 7 and 16.
- To identify if patients with inflammation (as indicated by elevated C-reactive protein
(CRP) and serum hepcidin levels or low soluble transferrin receptor (sTfR)/log ferritin
ratios) respond differently to darbepoetin alfa and iron therapy than patients without
OUTLINE: Patients are stratified according to severity of anemia (mild [hemoglobin ≥ 9.5
g/dL] vs severe [hemoglobin < 9.5 g/dL]), treatment with a platinum-containing regimen (yes
vs no), and gender. Patients are randomized to 1 of 3 treatment arms.
- Arm I: Patients receive darbepoetin alfa subcutaneously and sodium ferric gluconate
complex IV over 90 minutes on day 1.
- Arm II: Patients receive darbepoetin alfa as in arm I and oral ferrous sulfate once
daily on days 1-21.
- Arm III: Patients receive darbepoetin alfa as in arm I and oral placebo once daily on
In all arms, treatment repeats every 21 days for up to 15 weeks in the absence of
Patients complete quality-of-life (QOL) questionnaires in weeks 1, 7, and 16.
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Supportive Care
Hematopoietic Response Rate Defined as the Number of Participants Who Exhibit a Hematopoietic Response
Hematopoietic response was defined as Hemoglobin (Hb) increment of 2.0 g/dL from baseline or achievement of Hb >= 11 g/dL (whichever occurs first) in the absence of red blood cell transfusions during the preceding 28 days during the treatment period.
Charles L. Loprinzi, MD
United States: Food and Drug Administration
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