Darbepoetin Alfa With or Without Intravenous (IV) Iron

Study Overview
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Brief Summary
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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.

Official Title
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Once Per Cycle Treatment of Anemia With Darbepoetin Alfa With Iron in Subjects With Non Myeloid Malignancies

Conditions
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Anemia, Non-Myeloid Malignancies

Intervention / Treatment
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* Drug: darbepoetin alfa
* Drug: IV iron dextran


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Darbepoetin alfa 300 μg plus IV Iron<br>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). | Drug: darbepoetin alfa<br>* Darbepoetin alfa administered by subcutaneous injection.<br>* Other names: Aranesp®;Drug: IV iron dextran<br>* Administered by intravenous (IV) injection.<br>* Other names: Cosmofer®;|
| Experimental: Darbepoetin alfa 300 μg<br>Darbepoetin alfa 300 μg subcutaneous injection every three weeks (Q3W), for up to 15 weeks (a total of 5 doses). | Drug: darbepoetin alfa<br>* Darbepoetin alfa administered by subcutaneous injection.<br>* Other names: Aranesp®;|
| Experimental: Darbepoetin alfa 500 μg<br>Darbepoetin alfa 500 μg subcutaneous injection every three weeks (Q3W), for up to 15 weeks (a total of 5 doses). | Drug: darbepoetin alfa<br>* Darbepoetin alfa administered by subcutaneous injection.<br>* Other names: Aranesp®;|
| Active Comparator: Darbepoetin alfa 500 μg plus IV Iron<br>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). | Drug: darbepoetin alfa<br>* Darbepoetin alfa administered by subcutaneous injection.<br>* Other names: Aranesp®;Drug: IV iron dextran<br>* Administered by intravenous (IV) injection.<br>* Other names: Cosmofer®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Achieved the Target Hemoglobin Level, by Darbepoetin Alfa Dose | 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. | From Week 1 to Week 16 | 
| Number of Participants Who Achieved the Target Hemoglobin Levels, by IV Iron Usage | 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. | From Week 1 to Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Achieve Target Hemoglobin Level, by Darbepoetin Alfa Dose | 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. | From Week 1 to Week 16 | 
| Time to Achieve the Target Hemoglobin Level, by IV Iron Usage | 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. | From Week 1 to Week 16 | 
| Change From Baseline in Hemoglobin Concentration, by Darbepoetin Alfa Dose | Change in hemoglobin concentration from Baseline to the end of the treatment period (Week 16). | Baseline and Week 16 | 
| Change From Baseline in Hemoglobin Concentration, by IV Iron Usage | Change in hemoglobin concentration from Baseline to the end of the treatment period (Week 16). | Baseline and Week 16 | 
| Number of Participants With ≥ 1 Red Blood Cell Transfusion From Week 1 to End of Study, by Darbepoetin Alfa Dose | 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. | From Week 1 to Week 16 | 
| Number of Participants With ≥ 1 Red Blood Cell Transfusion From Week 1 to End of Study, by IV Iron Usage | 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. | From Week 1 to Week 16 | 
| Number of Participants With ≥ 1 Red Blood Cell Transfusion From Week 5 to End of Study | 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. | From Week 5 to Week 16 | 
| Number of Participants With a Hematopoietic Response, by Darbepoetin Alfa Dose | 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. | From Week 1 to Week 16 | 
| Number of Participants With a Hematopoietic Response, by IV Iron Usage | 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. | From Week 1 to Week 16 | 
| Time to Hematopoietic Response, by Darbepoetin Alfa Dose | 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. | From Week 1 to Week 16 | 
| Time to Hematopoietic Response, by IV Iron Usage | 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. | From Week 1 to Week 16 | 
| Change From Baseline in Functional Assessment of Cancer Therapy (FACT) - Fatigue Score, by Darbepoetin Alfa Dose | 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. | Baseline and Week 16 | 
| Change From Baseline in Functional Assessment of Cancer Therapy (FACT) - Fatigue Score, by IV Iron Usage | 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. | Baseline and Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anemia, chemotherapy induced anemia, darbepoetin alfa, cancer