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
Overview
- Phase
- Phase 3
- Intervention
- darbepoetin alfa
- Conditions
- Anemia
- Sponsor
- Mayo Clinic
- Enrollment
- 502
- Locations
- 2
- Primary Endpoint
- Hematopoietic Response Rate Defined as the Number of Participants Who Exhibit a Hematopoietic Response
- Status
- Completed
- Last Updated
- 14 years ago
Overview
Brief Summary
RATIONALE: Darbepoetin alfa may cause the body to make more red blood cells. Red blood cells contain iron that is needed to carry oxygen to the tissues. It is not yet known whether giving darbepoetin alfa (DA) together with intravenous iron or oral iron is more effective than giving darbepoetin alfa together with a placebo in treating anemia caused by chemotherapy.
PURPOSE: This randomized phase III trial is studying giving darbepoetin alfa together with iron to see how well it works compared with giving darbepoetin alfa together with a placebo in treating anemia caused by chemotherapy in patients with cancer.
Detailed Description
OBJECTIVES: Primary \* 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 chemotherapy-associated anemia. Secondary * 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 ≥ 11g/dL. * 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 inflammation. 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 days 1-21. In all arms, treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity. Patients complete quality-of-life (QOL) questionnaires in weeks 1, 7, and 16.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Arm I
Patients receive darbepoetin alfa subcutaneously and sodium ferric gluconate complex IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
Intervention: darbepoetin alfa
Arm I
Patients receive darbepoetin alfa subcutaneously and sodium ferric gluconate complex IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
Intervention: sodium ferric gluconate complex in sucrose
Arm II
Patients receive darbepoetin alfa as in arm I and oral ferrous sulfate once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
Intervention: darbepoetin alfa
Arm II
Patients receive darbepoetin alfa as in arm I and oral ferrous sulfate once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
Intervention: ferrous sulfate
Arm III
Patients receive darbepoetin alfa as in arm I and oral placebo once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
Intervention: darbepoetin alfa
Arm III
Patients receive darbepoetin alfa as in arm I and oral placebo once daily on days 1-21. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
Intervention: placebo
Outcomes
Primary Outcomes
Hematopoietic Response Rate Defined as the Number of Participants Who Exhibit a Hematopoietic Response
Time Frame: 16 Weeks
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.
Secondary Outcomes
- Mean Increment in Hemoglobin Level at Week 7(Baseline and 7 weeks)
- Ferritin Level at Baseline, Week 7 and Week 16(Baseline, 7 weeks and 16 weeks)
- Soluble Transferrin Receptor (sTfR)Level at Week 1, Week 7 and Week 16(1 week, 7 weeks and 16 weeks)
- Mean Corpuscular Volume (MCV) Level at Baseline, Week 7 and Week 16(Baseline, 7 weeks and 16 weeks)
- Incidence of Patients Receiving at Least One Red Blood Cell (RBC) Transfusions(Week 1 to Week 16)
- Mean Increment in Hemoglobin Level at Week 16(Baseline and 16 weeks)
- Change From Baseline in Overall Quality of Life (QOL) Score as Measured by the Linear Analogue Self Assessment (LASA)(Baseline and 16 weeks)
- Percentage of Patients Maintaining an Average Hemoglobin Level Within the National Comprehensive Cancer Network (NCCN) Range (11-13 g/dL) Through Week 16, Once Achieving a Hemoglobin of ≥ 11 g/dL(16 Weeks)
- Time to Hematopoietic Response(16 weeks)
- Time to First Red Blood Cell (RBC) Transfusions(16 weeks)
- C-reactive Protein (CRP) Level at Week 1, Week 7 and Week 16(1 Week, 7 Weeks and 16 Weeks)
- Transferrin Saturation at Baseline, Week 7 and Week 16(Baseline, 7 weeks and 16 weeks)
- Change From Baseline in Quality of Life (QOL) Score as Measured by Brief Fatigue Inventory(BFI) Fatigue Now Scale at End of Study(Baseline and 16 weeks)
- Change From Baseline in Quality of Life (QOL) Score as Measured by Symptom Distress Scale (SDS) at End of Study(Baseline and 16 weeks)
- Change From Baseline in Quality of Life (QOL) Score as Measured by The Functional Assessment of Cancer Therapy-Anemia (FACT-An) at End of Study(Baseline and 16 weeks)