Darbepoetin Alfa With or Without Intravenous (IV) Iron

Phase 2

Completed

Conditions: Non-Myeloid Malignancies
Anemia

Interventions: Drug: darbepoetin alfa
Drug: IV iron dextran

Registration Number: NCT00401544

Lead Sponsor: Amgen

Brief Summary: To deterime the efficacy of 500 μg and 300 μg darbepoetin alfa administered subcutaneously (SC) on an every 3 weeks (Q3W) schedule, and the effect of intravenous (IV) iron supplementation in the treatment of anemia in patients with non-myeloid malignancies who were receiving multicycle chemotherapy.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 243

Inclusion Criteria

Active non myeloid malignancy(cies) including lymphocytic leukemias
Received chemotherapy and expected to receive at least 8 additional weeks of cyclic cytotoxic chemotherapy
Anemia due to chemotherapy (screening Hgb <or = 10.0 g/dL)
at least 18 years of age at screening

Exclusion Criteria

Acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), or myelodysplastic syndromes (MDS)
Other underlying hematologic disorder, which could cause anemia, other than a non myeloid malignancy
Active bleeding
Severe, unstable, active chronic inflammatory disease (eg ulcerative disease, peptic ulcer disease, rheumatoid arthritis)
Active, unstable systemic or chronic infection
Planned elective surgery during the study where significant blood loss is expected
Unstable angina, or uncontrolled cardiac arrhythmia
Uncontrolled hypertension (diastolic blood pressure > 100 mmHg)
History of pure red cell aplasia (PRCA)
History of deep venous thrombosis
Known positive human immunodeficiency virus (HIV) test or acquired immune deficiency syndrome (AIDS) status
Any red-blood-cell (RBC) transfusion within 28 days before randomization and/or during screening
Currently receiving thalidomide or lenalidomide without prophylactic anticoagulant therapy
Currently receiving or planned to receive myeloablative radiation therapy
Received bone marrow or stem cell transplant in the 6 months prior to screening or planned during the study
Received any erythropoietic therapy within 28 days before randomization and/or during screening (eg rHuEPO or darbepoetin alfa)
Known sensitivity to any erythropoietic agents, the investigational product or its excipients to be administered during this study
Known sensitivity to iron administration
Pregnant or breast feeding

Study & Design

Study Type: INTERVENTIONAL

Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Darbepoetin alfa 500 μg plus IV Iron	IV iron dextran	Darbepoetin alfa 500 μg subcutaneous injection plus intravenous (IV) iron 400 mg, every three weeks (Q3W), for up to 15 weeks (a total of 5 doses).
Darbepoetin alfa 300 μg plus IV Iron	IV iron dextran	Darbepoetin alfa 300 μg subcutaneous injection plus intravenous (IV) iron 400 mg, every three weeks (Q3W), for up to 15 weeks (a total of 5 doses).
Darbepoetin alfa 500 μg	darbepoetin alfa	Darbepoetin alfa 500 μg subcutaneous injection every three weeks (Q3W), for up to 15 weeks (a total of 5 doses).
Darbepoetin alfa 300 μg plus IV Iron	darbepoetin alfa	Darbepoetin alfa 300 μg subcutaneous injection plus intravenous (IV) iron 400 mg, every three weeks (Q3W), for up to 15 weeks (a total of 5 doses).
Darbepoetin alfa 300 μg	darbepoetin alfa	Darbepoetin alfa 300 μg subcutaneous injection every three weeks (Q3W), for up to 15 weeks (a total of 5 doses).
Darbepoetin alfa 500 μg plus IV Iron	darbepoetin alfa	Darbepoetin alfa 500 μg subcutaneous injection plus intravenous (IV) iron 400 mg, every three weeks (Q3W), for up to 15 weeks (a total of 5 doses).

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Achieved the Target Hemoglobin Level, by Darbepoetin Alfa Dose	From Week 1 to Week 16	Target hemoglobin was defined as ≥ 11 g/dL during the treatment period in the absence of a red blood cell (RBC) transfusion on the day of measurement or during the preceding 28 days.
Number of Participants Who Achieved the Target Hemoglobin Levels, by IV Iron Usage	From Week 1 to Week 16	Target hemoglobin was defined as ≥ 11 g/dL during the treatment period in the absence of a red blood cell (RBC) transfusion on the day of measurement or during the preceding 28 days.

Secondary Outcome Measures

Name	Time	Method
Time to Achieve Target Hemoglobin Level, by Darbepoetin Alfa Dose	From Week 1 to Week 16	The time to target hemoglobin is the interval in weeks between study day 1 and the first day that a hemoglobin value ≥ 11.0 g/dL is observed during the treatment period. If a participant did not achieve the target hemoglobin by the time of withdrawal or the end of the treatment period (EOTP), the time to target hemoglobin was censored on the day of the last hemoglobin measurement or the EOTP, whichever was earlier. Median was calculated using Kaplan-Meier estimates.
Time to Achieve the Target Hemoglobin Level, by IV Iron Usage	From Week 1 to Week 16	The time to target hemoglobin is the interval in weeks between study day 1 and the first day that a hemoglobin value ≥ 11.0 g/dL is observed during the treatment period. If a participant did not achieve the target hemoglobin by the time of withdrawal or the end of the treatment period (EOTP), the time to target hemoglobin was censored on the day of the last hemoglobin measurement or the EOTP, whichever was earlier. Median was calculated using Kaplan-Meier estimates.
Change From Baseline in Hemoglobin Concentration, by Darbepoetin Alfa Dose	Baseline and Week 16	Change in hemoglobin concentration from Baseline to the end of the treatment period (Week 16).
Change From Baseline in Hemoglobin Concentration, by IV Iron Usage	Baseline and Week 16	Change in hemoglobin concentration from Baseline to the end of the treatment period (Week 16).
Number of Participants With ≥ 1 Red Blood Cell Transfusion From Week 1 to End of Study, by Darbepoetin Alfa Dose	From Week 1 to Week 16	The number of participants with ≥ 1 red blood cell (RBC) transfusion from week 1 to end of study (EOS). Participants with a hemoglobin value ≤ 8 g/dL but no RBC transfusion were counted as having had a transfusion.
Number of Participants With ≥ 1 Red Blood Cell Transfusion From Week 1 to End of Study, by IV Iron Usage	From Week 1 to Week 16	The number of participants with ≥ 1 red blood cell (RBC) transfusion from week 1 to end of study (EOS). Participants with a hemoglobin value ≤ 8 g/dL but no RBC transfusion were counted as having had a transfusion.
Number of Participants With ≥ 1 Red Blood Cell Transfusion From Week 5 to End of Study	From Week 5 to Week 16	Number of participants with ≥ 1 RBC transfusion from Week 5 to end of study (Week 16)). Participants with a hemoglobin value ≤ 8 g/dL but no RBC transfusion were counted as having had a transfusion.
Number of Participants With a Hematopoietic Response, by Darbepoetin Alfa Dose	From Week 1 to Week 16	Number of participants with a hematopoietic response, defined as \> 2 g/dL increase from baseline or hemoglobin ≥ 12 g/dL during the treatment period in the absence of a red blood cell transfusion within the prior 28 days.
Number of Participants With a Hematopoietic Response, by IV Iron Usage	From Week 1 to Week 16	Number of participants with a hematopoietic response, defined as \> 2 g/dL increase from baseline or hemoglobin ≥ 12 g/dL during the treatment period in the absence of a red blood cell transfusion within the prior 28 days. Assessing the effect of iron in a factorial experiment.
Time to Hematopoietic Response, by Darbepoetin Alfa Dose	From Week 1 to Week 16	The time to hematopoietic response is the interval in weeks between study day 1 and the first day that a hematopoietic response is observed during the treatment period. Hematopoietic response is defined as an increase in hemoglobin concentration of ≥ 2.0 g/dL from baseline or a hemoglobin concentration ≥ 12.0 g/dL in the absence of RBC transfusions on the day of measurement and during the preceding 28 days of the treatment period. If a participant did not achieve a hematopoietic response by the time of withdrawal or the end of the treatment period (EOTP), the time to hematopoietic response was censored on the day of the last hemoglobin measurement or the EOTP, whichever was earlier. Median was calculated using using Kaplan-Meier estimates.
Time to Hematopoietic Response, by IV Iron Usage	From Week 1 to Week 16	The time to hematopoietic response is the interval in weeks between study day 1 and the first day that a hematopoietic response is observed during the treatment period. Hematopoietic response is defined as an increase in hemoglobin concentration of ≥ 2.0 g/dL from baseline or a hemoglobin concentration ≥ 12.0 g/dL in the absence of RBC transfusions on the day of measurement and during the preceding 28 days of the treatment period. If a participant did not achieve a hematopoietic response by the time of withdrawal or the end of the treatment period (EOTP), the time to hematopoietic response was censored on the day of the last hemoglobin measurement or the EOTP, whichever was earlier. Median was calculated using using Kaplan-Meier estimates.
Change From Baseline in Functional Assessment of Cancer Therapy (FACT) - Fatigue Score, by Darbepoetin Alfa Dose	Baseline and Week 16	Health related quality of life was measured using the Functional Assessment of Cancer Therapy (FACT) - Fatigue subscale. The FACT-F includes 13 fatigue items, with each item assessed on a 5-point scale (ie, response values of 0 to 4). The FACT-F subscale score ranges from 0 to 52, where a higher score represents less fatigue.
Change From Baseline in Functional Assessment of Cancer Therapy (FACT) - Fatigue Score, by IV Iron Usage	Baseline and Week 16	Health related quality of life was measured using the Functional Assessment of Cancer Therapy (FACT) - Fatigue subscale. The FACT-F includes 13 fatigue items, with each item assessed on a 5-point scale (ie, response values of 0 to 4). The FACT-F subscale score ranges from 0 to 52, where a higher score represents less fatigue.