Anemia, Anemia of Cancer, Cancer, Carcinoma, Neoplasms, Non-Myeloid Malignancies
Conditions
Keywords
anemia of cancer, darbepoetin alfa, Aranesp
Brief summary
This phase 2, multicenter, randomized, open-label, comparative study was designed to determine the effect of darbepoetin alfa on hospital days, economic outcomes, and health related quality of life (HRQOL) in anemic patients with nonmyeloid malignancies who were not receiving chemotherapy. Participants were randomly assigned in a 4:1 allocation ratio to receive either 21 weeks of darbepoetin alfa treatment (treatment group) or 12 weeks of observation followed by up to 9 weeks of darbepoetin alfa treatment (observation group).
Interventions
BIOLOGICALdarbepoetin alfa
Administered subcutaneously.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* nonmyeloid malignancies (including lymphocytic leukemias) * anemia (hemoglobin concentration less than or equal to 11.0 g/dL) due to cancer and/or previous chemotherapy or radiotherapy * Eastern Cooperative Oncology Group performance status of 0 to 2 * adequate liver and renal functions * 18 years or older
Exclusion criteria
* history of recombinant human erythropoietin therapy, cytotoxic chemotherapy, or more than 30 Gy radiotherapy to the whole pelvis within 4 weeks before screening * acute myelogenous leukemia, chronic myelogenous leukemia, or myelodysplastic syndrome * known hematologic disorders that could cause anemia * inflammatory or cardiac disorders * previous positive antibody response to any erythropoietic agent * history of pure red cell aplasia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Hospitalized During the Test Period | Weeks 1- 12 | Number of participants hospitalized during Weeks 1-12 as self-reported in the Health Care Utilization portion of the Subject Outcome Questionaire. |
| Days of Hospitalization During the Test Period | Weeks 1-12 | Number of days hospitalized during Weeks 1-12 as self-reported in the Health Care Utilization portion of the Subject Outcome Questionaire; participants who were not hospitalized had a value of 0 days. |
| Number of Hospitalizations During the Test Period | Weeks 1-12 | Number of times participants were hospitalized as self-reported in the Health Care Utilization portion of the Subject Outcome Questionaire during Weeks 1-12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hematopoietic Response During the Test Period | Weeks 1-12 | The number of participants achieving a hematopoietic response, defined as an increase in hemoglobin from baseline of ≥ 2.0 g/dL or a concentration ≥ 12.0 g/dL both in the absence of red blood cell (RBC) transfusions during the preceding 28 days. |
| Change From Baseline in Hemoglobin Level | Baseline (Week 1) and Week 13 | The difference between hemoglobin concentrations after 12 weeks of treatment and the Baseline hemoglobin concentration value (Study Day 1 sample prior to first dose of darbepoetin alfa). |
| Number of Participants With Red Blood Cell (RBC) Transfusions During the Test Period | Weeks 1-12 | Number of participants with at least one RBC transfusion during Weeks 1 to 12. |
| Number of Units of Red Blood Cells Transfused During the Test Period | Weeks 1-12 | The average number of standard units of red blood cells transfused during Weeks 1 to 12. |
| Total Hospital Costs During the Test Period | Weeks 1-12 | The hospital bill database was used to determine the mean total hospital cost per participant during the test period. Participants who were not hospitalized had a cost of $0 imputed. |
| Number of Participants With Red Blood Cell (RBC) Transfusions During Weeks 5-12 | Weeks 5-12 | The number of participants with at least one RBC transfusion during weeks 5 to 12. |
| Number of Units of Red Blood Cells Transfused During Weeks 5-12 | Weeks 5-12 | The number of standard units of RBCs transfused during Weeks 5 to 12. |
| Number of Days of Red Blood Cell Transfusions During Weeks 5-12 | Weeks 5-12 | The number of days when at least one RBC transfusion was administered during Weeks 5 to 12. |
| Number of Days of Red Blood Cell Transfusions During the Test Period | Weeks 1-12 | The number of days when at least one red blood cell transfusion was administered during Weeks 1 to 12. |
| Change in Functional Assessment of Cancer Therapy (FACT)-Fatigue Score at Week 13 | Baseline (Week 1) and Week 13 | The FACT-Fatigue scale comprises 13 questions evaluating the impact of anemia on cancer patients with various tumor types receiving chemotherapy. Fatigue scores range from 0 to 52, with a higher score indicating less fatigue. |
| Hemoglobin Response During the Test Period | Weeks 1-12 | The number of participants achieving a hemoglobin response, defined as an increase in hemoglobin from baseline of ≥ 2.0 g/dL in the absence of red blood cell (RBC) transfusions during the preceding 28 days. |
Participant flow
Recruitment details
First Patient Randomized: 24-Jun-2002 Last Patient Randomized: 08-Aug-2003
Participants by arm
| Arm | Count |
|---|---|
| Darbepoetin Alfa 3 μg/kg Participants in the treatment group received darbepoetin alfa subcutaneously (SC) at a dose of 3.0 μg/kg once every 2 weeks for 21 weeks. The dose of darbepoetin alfa could be increased at Week 7 (to 5.0 μg/kg once every 2 weeks) or at Week 13 (to 9.0 μg/kg once every 2 weeks) in participants with a hemoglobin change from baseline of less than 1.0 g/dL who dose escalated at Week 7. | 226 |
| Observation Participants in the observation group were evaluated once every 2 weeks for the first 12 weeks (test period). No darbepoetin alfa was administered during this period. Darbepoetin alfa could be initiated at a dose of 3.0 μg/kg once every 2 weeks beginning with the first visit after the test period at which the participant's hemoglobin concentration was less than or equal to 11.0 g/dL. The dose of darbepoetin alfa could be increased to 5.0 μg/kg once every 2 weeks after 6 weeks of darbepoetin alfa treatment in participants with a hemoglobin change from baseline of less than 1.0 g/dL. | 59 |
| Total | 285 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 20 | 1 |
| Overall Study | Chemotherapy initiated | 12 | 4 |
| Overall Study | Death | 14 | 2 |
| Overall Study | Did not receive study drug | 2 | 0 |
| Overall Study | Erythropoietin therapy initiated | 2 | 0 |
| Overall Study | Ineligibility determined | 3 | 3 |
| Overall Study | Lost to Follow-up | 6 | 2 |
| Overall Study | Other | 3 | 1 |
| Overall Study | Physician Decision | 9 | 6 |
| Overall Study | Protocol deviation | 2 | 0 |
| Overall Study | Withdrawal by Subject | 17 | 9 |
Baseline characteristics
| Characteristic | Observation | Total | Darbepoetin Alfa 3 μg/kg |
|---|---|---|---|
| Age, Continuous | 67.2 Years STANDARD_DEVIATION 12.5 | 70.8 Years STANDARD_DEVIATION 11 | 71.7 Years STANDARD_DEVIATION 10.4 |
| Race/Ethnicity, Customized Asian | 1 Participant | 6 Participant | 5 Participant |
| Race/Ethnicity, Customized Black | 12 Participant | 40 Participant | 28 Participant |
| Race/Ethnicity, Customized Other | 0 Participant | 5 Participant | 5 Participant |
| Race/Ethnicity, Customized White | 46 Participant | 234 Participant | 188 Participant |
| Sex: Female, Male Female | 36 Participants | 167 Participants | 131 Participants |
| Sex: Female, Male Male | 23 Participants | 118 Participants | 95 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 99 / 226 | 21 / 33 | 6 / 26 |
| serious Total, serious adverse events | 65 / 226 | 4 / 33 | 4 / 26 |
Outcome results
Primary
Days of Hospitalization During the Test Period
Number of days hospitalized during Weeks 1-12 as self-reported in the Health Care Utilization portion of the Subject Outcome Questionaire; participants who were not hospitalized had a value of 0 days.
Time frame: Weeks 1-12
Population: Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm. Patients also needed to have completed the baseline and at least 1 post-baseline subject outcome questionaire.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Darbepoetin Alfa 3 μg/kg | Days of Hospitalization During the Test Period | 0.5 days | Standard Deviation 2.2 |
| Observation | Days of Hospitalization During the Test Period | 0.5 days | Standard Deviation 1.7 |
Primary
Number of Hospitalizations During the Test Period
Number of times participants were hospitalized as self-reported in the Health Care Utilization portion of the Subject Outcome Questionaire during Weeks 1-12
Time frame: Weeks 1-12
Population: Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm. Patients also needed to have completed the baseline and at least 1 post-baseline subject outcome questionaire.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Darbepoetin Alfa 3 μg/kg | Number of Hospitalizations During the Test Period | 0.1 hospitalizations | Standard Deviation 0.5 |
| Observation | Number of Hospitalizations During the Test Period | 0.2 hospitalizations | Standard Deviation 0.4 |
Primary
Number of Participants Hospitalized During the Test Period
Number of participants hospitalized during Weeks 1-12 as self-reported in the Health Care Utilization portion of the Subject Outcome Questionaire.
Time frame: Weeks 1- 12
Population: Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm. Patients also needed to have completed the baseline and at least 1 post-baseline subject outcome questionaire.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Darbepoetin Alfa 3 μg/kg | Number of Participants Hospitalized During the Test Period | 23 Participants |
| Observation | Number of Participants Hospitalized During the Test Period | 6 Participants |
Secondary
Change From Baseline in Hemoglobin Level
The difference between hemoglobin concentrations after 12 weeks of treatment and the Baseline hemoglobin concentration value (Study Day 1 sample prior to first dose of darbepoetin alfa).
Time frame: Baseline (Week 1) and Week 13
Population: Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm. Patients also needed to have a baseline hemoglobin that was not affected by a red blood cell transfusion. LVCF imputation was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Darbepoetin Alfa 3 μg/kg | Change From Baseline in Hemoglobin Level | 2.1 g/dL | Standard Deviation 1.9 |
| Observation | Change From Baseline in Hemoglobin Level | 0.1 g/dL | Standard Deviation 0.8 |
Secondary
Change in Functional Assessment of Cancer Therapy (FACT)-Fatigue Score at Week 13
The FACT-Fatigue scale comprises 13 questions evaluating the impact of anemia on cancer patients with various tumor types receiving chemotherapy. Fatigue scores range from 0 to 52, with a higher score indicating less fatigue.
Time frame: Baseline (Week 1) and Week 13
Population: Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm. Participants also needed to have completed the baseline and at least 1 post-baseline FACT-Fatigue questionaire. Last Value Carried Forward (LVCF) imputation used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Darbepoetin Alfa 3 μg/kg | Change in Functional Assessment of Cancer Therapy (FACT)-Fatigue Score at Week 13 | 6.0 units on a scale | Standard Deviation 12 |
| Observation | Change in Functional Assessment of Cancer Therapy (FACT)-Fatigue Score at Week 13 | 2.2 units on a scale | Standard Deviation 7.6 |
Secondary
Hematopoietic Response During the Test Period
The number of participants achieving a hematopoietic response, defined as an increase in hemoglobin from baseline of ≥ 2.0 g/dL or a concentration ≥ 12.0 g/dL both in the absence of red blood cell (RBC) transfusions during the preceding 28 days.
Time frame: Weeks 1-12
Population: Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm. Patients also needed to have a baseline hemoglobin that was not affected by a red blood cell transfusion.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Darbepoetin Alfa 3 μg/kg | Hematopoietic Response During the Test Period | 145 Participants |
| Observation | Hematopoietic Response During the Test Period | 10 Participants |
Secondary
Hemoglobin Response During the Test Period
The number of participants achieving a hemoglobin response, defined as an increase in hemoglobin from baseline of ≥ 2.0 g/dL in the absence of red blood cell (RBC) transfusions during the preceding 28 days.
Time frame: Weeks 1-12
Population: Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm. Patients also needed to have a baseline hemoglobin that was not affected by a red blood cell transfusion.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Darbepoetin Alfa 3 μg/kg | Hemoglobin Response During the Test Period | 128 Participants |
| Observation | Hemoglobin Response During the Test Period | 4 Participants |
Secondary
Number of Days of Red Blood Cell Transfusions During the Test Period
The number of days when at least one red blood cell transfusion was administered during Weeks 1 to 12.
Time frame: Weeks 1-12
Population: Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Darbepoetin Alfa 3 μg/kg | Number of Days of Red Blood Cell Transfusions During the Test Period | 0.2 days | Standard Deviation 0.6 |
| Observation | Number of Days of Red Blood Cell Transfusions During the Test Period | 0.4 days | Standard Deviation 1 |
Secondary
Number of Days of Red Blood Cell Transfusions During Weeks 5-12
The number of days when at least one RBC transfusion was administered during Weeks 5 to 12.
Time frame: Weeks 5-12
Population: Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm, and who were on-study as of the beginning of Week 5 (Study Day 29).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Darbepoetin Alfa 3 μg/kg | Number of Days of Red Blood Cell Transfusions During Weeks 5-12 | 0.1 days | Standard Deviation 0.5 |
| Observation | Number of Days of Red Blood Cell Transfusions During Weeks 5-12 | 0.4 days | Standard Deviation 0.8 |
Secondary
Number of Participants With Red Blood Cell (RBC) Transfusions During the Test Period
Number of participants with at least one RBC transfusion during Weeks 1 to 12.
Time frame: Weeks 1-12
Population: Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm with available data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Darbepoetin Alfa 3 μg/kg | Number of Participants With Red Blood Cell (RBC) Transfusions During the Test Period | 25 Participants |
| Observation | Number of Participants With Red Blood Cell (RBC) Transfusions During the Test Period | 11 Participants |
Secondary
Number of Participants With Red Blood Cell (RBC) Transfusions During Weeks 5-12
The number of participants with at least one RBC transfusion during weeks 5 to 12.
Time frame: Weeks 5-12
Population: Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm, and who were on-study as of the beginning of Week 5 (Study Day 29).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Darbepoetin Alfa 3 μg/kg | Number of Participants With Red Blood Cell (RBC) Transfusions During Weeks 5-12 | 16 Participants |
| Observation | Number of Participants With Red Blood Cell (RBC) Transfusions During Weeks 5-12 | 10 Participants |
Secondary
Number of Units of Red Blood Cells Transfused During the Test Period
The average number of standard units of red blood cells transfused during Weeks 1 to 12.
Time frame: Weeks 1-12
Population: Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Darbepoetin Alfa 3 μg/kg | Number of Units of Red Blood Cells Transfused During the Test Period | 0.4 units of red blood cells | Standard Deviation 1.4 |
| Observation | Number of Units of Red Blood Cells Transfused During the Test Period | 0.9 units of red blood cells | Standard Deviation 2.4 |
Secondary
Number of Units of Red Blood Cells Transfused During Weeks 5-12
The number of standard units of RBCs transfused during Weeks 5 to 12.
Time frame: Weeks 5-12
Population: Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm, and who were on-study as of the beginning of week 5 (study day 29).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Darbepoetin Alfa 3 μg/kg | Number of Units of Red Blood Cells Transfused During Weeks 5-12 | 0.2 units of red blood cells | Standard Deviation 1 |
| Observation | Number of Units of Red Blood Cells Transfused During Weeks 5-12 | 0.8 units of red blood cells | Standard Deviation 1.8 |
Secondary
Total Hospital Costs During the Test Period
The hospital bill database was used to determine the mean total hospital cost per participant during the test period. Participants who were not hospitalized had a cost of $0 imputed.
Time frame: Weeks 1-12
Population: Includes all randomized patients in the darbepoetin alfa arm who received at least 1 dose of study drug or all randomized patients in the observation arm, and were included in the hospital bill database. Participants who were not hospitalized had a cost of $0 imputed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Darbepoetin Alfa 3 μg/kg | Total Hospital Costs During the Test Period | 1474.58 dollars | Standard Deviation 5528.61 |
| Observation | Total Hospital Costs During the Test Period | 487.31 dollars | Standard Deviation 1821.43 |