Anemia, Leukemia, Lymphoma, Lymphoproliferative Disorder, Multiple Myeloma and Plasma Cell Neoplasm, Precancerous Condition, Unspecified Adult Solid Tumor, Protocol Specific
Conditions
Keywords
unspecified adult solid tumor, protocol specific, monoclonal gammopathy of undetermined significance, extramedullary plasmacytoma, isolated plasmacytoma of bone, refractory multiple myeloma, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, primary systemic amyloidosis, Waldenstrom macroglobulinemia, post-transplant lymphoproliferative disorder, stage I adult T-cell leukemia/lymphoma, stage II adult T-cell leukemia/lymphoma, stage III adult T-cell leukemia/lymphoma, stage IV adult T-cell leukemia/lymphoma, recurrent adult T-cell leukemia/lymphoma, angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, stage I cutaneous T-cell non-Hodgkin lymphoma, stage II cutaneous T-cell non-Hodgkin lymphoma, stage III cutaneous T-cell non-Hodgkin lymphoma, stage IV cutaneous T-cell non-Hodgkin lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, stage I mycosis fungoides/Sezary syndrome, stage II mycosis fungoides/Sezary syndrome, stage III mycosis fungoides/Sezary syndrome, stage IV mycosis fungoides/Sezary syndrome, recurrent mycosis fungoides/Sezary syndrome, stage I adult Hodgkin lymphoma, stage II adult Hodgkin lymphoma, stage III adult Hodgkin lymphoma, stage IV adult Hodgkin lymphoma, recurrent adult Hodgkin lymphoma, recurrent adult grade III lymphomatoid granulomatosis, stage I adult Burkitt lymphoma, stage III adult Burkitt lymphoma, stage IV adult Burkitt lymphoma, noncontiguous stage II adult Burkitt lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse mixed cell lymphoma, noncontiguous stage II adult diffuse small cleaved cell lymphoma, noncontiguous stage II adult immunoblastic large cell lymphoma, noncontiguous stage II adult lymphoblastic lymphoma, noncontiguous stage II grade 1 follicular lymphoma, noncontiguous stage II grade 2 follicular lymphoma, noncontiguous stage II grade 3 follicular lymphoma, noncontiguous stage II mantle cell lymphoma, noncontiguous stage II marginal zone lymphoma, noncontiguous stage II small lymphocytic lymphoma, contiguous stage II adult Burkitt lymphoma, contiguous stage II adult diffuse large cell lymphoma, contiguous stage II adult diffuse mixed cell lymphoma, contiguous stage II adult diffuse small cleaved cell lymphoma, contiguous stage II adult immunoblastic large cell lymphoma, contiguous stage II adult lymphoblastic lymphoma, contiguous stage II grade 1 follicular lymphoma, contiguous stage II grade 2 follicular lymphoma, contiguous stage II grade 3 follicular lymphoma, contiguous stage II mantle cell lymphoma, contiguous stage II marginal zone lymphoma, contiguous stage II small lymphocytic lymphoma, stage I adult diffuse large cell lymphoma, stage I adult diffuse mixed cell lymphoma, stage I adult diffuse small cleaved cell lymphoma, stage III adult diffuse large cell lymphoma, stage III adult diffuse mixed cell lymphoma, stage III adult diffuse small cleaved cell lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage I adult immunoblastic large cell lymphoma, stage III adult immunoblastic large cell lymphoma, stage IV adult immunoblastic large cell lymphoma, stage I adult lymphoblastic lymphoma, stage III adult lymphoblastic lymphoma, stage IV adult lymphoblastic lymphoma, stage I grade 1 follicular lymphoma, stage I grade 2 follicular lymphoma, stage I grade 3 follicular lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, stage I mantle cell lymphoma, stage I marginal zone lymphoma, stage III mantle cell lymphoma, stage III marginal zone lymphoma, stage IV mantle cell lymphoma, stage IV marginal zone lymphoma, stage I small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, recurrent adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, adult acute lymphoblastic leukemia in remission, recurrent adult acute lymphoblastic leukemia, untreated adult acute lymphoblastic leukemia, stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, refractory chronic lymphocytic leukemia, refractory hairy cell leukemia, progressive hairy cell leukemia, initial treatment, prolymphocytic leukemia, anemia, T-cell large granular lymphocyte leukemia, acute undifferentiated leukemia, mast cell leukemia, adult nasal type extranodal NK/T-cell lymphoma, untreated hairy cell leukemia
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.
Interventions
BIOLOGICALdarbepoetin alfa
Given by injection
DIETARY_SUPPLEMENTferrous sulfate
Given by mouth
Given by IV
OTHERplacebo
Given by mouth
Sponsors
National Cancer Institute (NCI)
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Diagnosis of a non-myeloid cancer (other than non-melanomatous skin cancer) * Receiving or scheduled to receive chemotherapy (biological agents, such as small molecules/tyrosine kinase inhibitors and antibody-based therapies, are allowed) * Has chemotherapy-related anemia (hemoglobin \< 11 g/dL) * No anemia known to be secondary to gastrointestinal bleeding or hemolysis * No anemia known to be secondary to vitamin B12 or folic acid deficiency \+ Vitamin B12 and folic acid deficiency must be ruled out if the mean corpuscular volume (MCV) is \> 100 fL * No anemia secondary to chemotherapy-induced myelodysplastic syndromes * No primary hematologic disorder causing moderate to severe anemia (e.g., congenital dyserythropoietic anemia, homozygous hemoglobin S disease or compound heterozygous sickling states, or thalassemia major) \- Carriers for these disease states are eligible * No first-degree relative with primary hemochromatosis (unless the patient has undergone HFE genotyping and was found to have at least one wild-type allele, while the proband in the family demonstrated to have either the common C282Y or H63D mutation) PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Ferritin \> 20 mcg/L (i.e., not obviously iron deficient) * ALT or AST \< 5 times upper limit of normal * Alert, mentally competent, and able to sign informed consent * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 3 months after completion of study treatment * Willing or able to be randomized and undergo study treatment * Willing or able to fill out quality-of-life forms * No uncontrolled hypertension (i.e., systolic blood pressure \[BP\] ≥ 180 mm Hg or diastolic BP ≥ 100 mm Hg) * No history of uncontrolled cardiac arrhythmias * No pulmonary embolism or deep venous thrombosis within the past year (unless the patient is on anticoagulation therapy and planning to continue it during study participation) * No known hypersensitivity to darbepoetin alfa, erythropoietin, mammalian cell-derived products, iron, or human albumin * No seizures within the past 3 months * No gastrointestinal conditions expected to cause significant impairment of oral iron, such as untreated celiac disease or amyloidosis involving the gut - Patients with celiac disease who are adhering to a gluten-free diet are eligible PRIOR CONCURRENT THERAPY: * See Disease Characteristics * More than 3 months since prior darbepoetin alfa, epoetin alfa, or any investigational forms of erythropoietin (e.g., gene-activated erythropoietin or novel erythropoiesis-stimulating protein) * More than 1 year since prior peripheral blood stem cell or bone marrow transplantation * More than 2 weeks since prior red blood cell transfusions * More than 14 days since prior major surgery * No prior gastrectomy or resection of \> 100 cm of small intestine * Not planning to undergo stem cell or bone marrow transplantation within the next 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hematopoietic Response Rate Defined as the Number of Participants Who Exhibit a Hematopoietic Response | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Incidence of Patients Receiving at Least One Red Blood Cell (RBC) Transfusions | Week 1 to Week 16 | — |
| Mean Increment in Hemoglobin Level at Week 7 | Baseline and 7 weeks | Value at 7 weeks minus value at baseline. |
| Mean Increment in Hemoglobin Level at Week 16 | Baseline and 16 weeks | Value at 16 weeks minus value at baseline. |
| Time to Hematopoietic Response | 16 weeks | Hematopoietic response was defined as 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. |
| Time to First Red Blood Cell (RBC) Transfusions | 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 | Overall QOL item score range: 0 (Worst) to 10 (Best), ordinal. Change: score at 16 weeks minus score at baseline. |
| C-reactive Protein (CRP) Level at Week 1, Week 7 and Week 16 | 1 Week, 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 | Fatigue Now Scale range: 0 (No Fatigue) to 10 (Worst), ordinal. Change: score at 16 weeks minus score at baseline. |
| 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 | FACT-AN Scale range: 0 (Worst) to 100 (Best), ordinal. Change: score at 16 weeks minus score at baseline. A clinically significant result will be defined as a shift of 10 points on a 0-100 point transformed scale between the average QOL scores of the 3 variants of iron therapy. |
| Soluble Transferrin Receptor (sTfR)Level at Week 1, Week 7 and Week 16 | 1 week, 7 weeks and 16 weeks | — |
| Ferritin Level at Baseline, Week 7 and Week 16 | Baseline, 7 weeks and 16 weeks | — |
| Mean Corpuscular Volume (MCV) Level at Baseline, Week 7 and Week 16 | Baseline, 7 weeks and 16 weeks | MCV is a measure of the average red blood cell volume. |
| 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 Symptom Distress Scale (SDS) at End of Study | Baseline and 16 weeks | SDS Scale range: 0 (Worst), 100 (Best), ordinal. Change: score at 16 weeks minus score at baseline. A clinically significant result will be defined as a shift of 10 points on a 0-100 point transformed scale between the average QOL scores of the 3 variants of iron therapy. |
Countries
United States
Participant flow
Recruitment details
Five-hundred and two (502) participants were recruited between February 2006 and December 2008 at Mayo Clinic Cancer Research Consortium (MCCRC) sites.
Pre-assignment details
Eight patients canceled before the first dose of darbepoetin alfa (DA) (3 DA + Intravenously (IV) Iron, 3 DA + Oral Iron and 2 DA + Placebo); and 4 patients were ineligible (2 DA + Oral Iron, 2 DA + Placebo). These 12 patients were excluded from all analysis.
Participants by arm
| Arm | Count |
|---|---|
| DA + IV Iron Patients receive darbepoetin alfa (DA) subcutaneously and sodium ferric gluconate complex intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity. | 164 |
| DA + Oral Iron Patients receive darbepoetin alfa (DA) 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. | 163 |
| DA + Placebo Patients receive darbepoetin alfa (DA) 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. | 163 |
| Total | 490 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 11 | 5 | 8 |
| Overall Study | Alternative Treatment | 1 | 0 | 0 |
| Overall Study | Death | 8 | 6 | 3 |
| Overall Study | Other Medical Problems | 4 | 4 | 9 |
| Overall Study | Other Reasons | 5 | 12 | 23 |
| Overall Study | Withdrawal by Subject | 30 | 23 | 14 |
Baseline characteristics
| Characteristic | DA + IV Iron | DA + Oral Iron | DA + Placebo | Total |
|---|---|---|---|---|
| Age Continuous | 64 years STANDARD_DEVIATION 11 | 63 years STANDARD_DEVIATION 13 | 63 years STANDARD_DEVIATION 11 | 63 years STANDARD_DEVIATION 12 |
| Baseline Ferritin | 460.5 µg/L STANDARD_DEVIATION 526.99 | 479.5 µg/L STANDARD_DEVIATION 484.15 | 456.0 µg/L STANDARD_DEVIATION 479.27 | 465.3 µg/L STANDARD_DEVIATION 496.41 |
| Baseline Transferrin Saturation | 22.5 Percentage Saturation STANDARD_DEVIATION 12.81 | 19.6 Percentage Saturation STANDARD_DEVIATION 11.7 | 22.2 Percentage Saturation STANDARD_DEVIATION 13.36 | 21.5 Percentage Saturation STANDARD_DEVIATION 12.69 |
| Degree of Anemia Mild: Hemoglobin>=9.5 | 123 Participants | 123 Participants | 123 Participants | 369 Participants |
| Degree of Anemia Severe: Hemoglobin <9.5 | 41 Participants | 40 Participants | 40 Participants | 121 Participants |
| Height | 166.9 cm STANDARD_DEVIATION 9.44 | 167.7 cm STANDARD_DEVIATION 8.93 | 166.8 cm STANDARD_DEVIATION 9.36 | 167.1 cm STANDARD_DEVIATION 9.24 |
| Platinum-Containing Regimen No | 85 Participants | 84 Participants | 85 Participants | 254 Participants |
| Platinum-Containing Regimen Yes | 79 Participants | 79 Participants | 78 Participants | 236 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 7 Participants | 4 Participants | 17 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants | 1 Participants | 7 Participants |
| Race (NIH/OMB) White | 155 Participants | 147 Participants | 156 Participants | 458 Participants |
| Sex: Female, Male Female | 109 Participants | 106 Participants | 105 Participants | 320 Participants |
| Sex: Female, Male Male | 55 Participants | 57 Participants | 58 Participants | 170 Participants |
| Tumor Type Both | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Tumor Type Hematologic Neoplasm | 6 Participants | 8 Participants | 11 Participants | 25 Participants |
| Tumor Type Solid Tumor | 157 Participants | 154 Participants | 151 Participants | 462 Participants |
| Weight | 77.4 kg STANDARD_DEVIATION 18.74 | 79.4 kg STANDARD_DEVIATION 19.75 | 76.4 kg STANDARD_DEVIATION 17.68 | 77.7 kg STANDARD_DEVIATION 18.75 |
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 | 150 / 164 | 147 / 163 | 141 / 163 |
| serious Total, serious adverse events | 5 / 164 | 3 / 163 | 2 / 163 |
Outcome results
Primary
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.
Time frame: 16 Weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DA + IV Iron | Hematopoietic Response Rate Defined as the Number of Participants Who Exhibit a Hematopoietic Response | Yes | 114 Participants |
| DA + IV Iron | Hematopoietic Response Rate Defined as the Number of Participants Who Exhibit a Hematopoietic Response | No | 50 Participants |
| DA + Oral Iron | Hematopoietic Response Rate Defined as the Number of Participants Who Exhibit a Hematopoietic Response | Yes | 109 Participants |
| DA + Oral Iron | Hematopoietic Response Rate Defined as the Number of Participants Who Exhibit a Hematopoietic Response | No | 54 Participants |
| DA + Placebo | Hematopoietic Response Rate Defined as the Number of Participants Who Exhibit a Hematopoietic Response | Yes | 106 Participants |
| DA + Placebo | Hematopoietic Response Rate Defined as the Number of Participants Who Exhibit a Hematopoietic Response | No | 57 Participants |
Comparison: With 176 evaluable participants per treatment arm, there would have been \>=80% power to detect a difference across two treatment arms of 15% in the primary hematopoietic response endpoint through Fisher's exact test, if the true percentage of patients that experience a hematopoietic response was at least 30% in the superior group, with a 2.5% type I error rate.p-value: 0.39Fisher Exact
Comparison: With 176 evaluable participants per treatment arm, there would have been \>=80% power to detect a difference across two treatment arms of 15% in the primary hematopoietic response endpoint through Fisher's exact test, if the true percentage of patients that experience a hematopoietic response was at least 30% in the superior group, with a 2.5% type I error rate.p-value: 0.73Fisher Exact
Secondary
Change From Baseline in Overall Quality of Life (QOL) Score as Measured by the Linear Analogue Self Assessment (LASA)
Overall QOL item score range: 0 (Worst) to 10 (Best), ordinal. Change: score at 16 weeks minus score at baseline.
Time frame: Baseline and 16 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DA + IV Iron | Change From Baseline in Overall Quality of Life (QOL) Score as Measured by the Linear Analogue Self Assessment (LASA) | 0.4 Scores on a scale | Standard Deviation 2.18 |
| DA + Oral Iron | Change From Baseline in Overall Quality of Life (QOL) Score as Measured by the Linear Analogue Self Assessment (LASA) | 0.2 Scores on a scale | Standard Deviation 2.23 |
| DA + Placebo | Change From Baseline in Overall Quality of Life (QOL) Score as Measured by the Linear Analogue Self Assessment (LASA) | 0.5 Scores on a scale | Standard Deviation 2.28 |
Comparison: With 176 evaluable participants per treatment arm, there would have been \>=80% power to detect a difference across two treatment arms of 33% of the standard deviation in participant QOL through t-test/Wilcoxon test, with a 2.5% type I error rate. A 10 points shift on a 0-100 point scale in QOL measures is generally considered clinically relevant and specifically important in the use of UNISCALE, BFI and FACT-An.p-value: 0.61t-test, 2 sided
Comparison: With 176 evaluable participants per treatment arm, there would have been \>=80% power to detect a difference across two treatment arms of 33% of the standard deviation in participant QOL through t-test/Wilcoxon test, with a 2.5% type I error rate. A 10 points shift on a 0-100 point scale in QOL measures is generally considered clinically relevant and specifically important in the use of UNISCALE, BFI and FACT-An.p-value: 0.44t-test, 2 sided
Secondary
Change From Baseline in Quality of Life (QOL) Score as Measured by Brief Fatigue Inventory(BFI) Fatigue Now Scale at End of Study
Fatigue Now Scale range: 0 (No Fatigue) to 10 (Worst), ordinal. Change: score at 16 weeks minus score at baseline.
Time frame: Baseline and 16 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DA + IV Iron | Change From Baseline in Quality of Life (QOL) Score as Measured by Brief Fatigue Inventory(BFI) Fatigue Now Scale at End of Study | -1.1 Scores on a scale | Standard Deviation 3.08 |
| DA + Oral Iron | Change From Baseline in Quality of Life (QOL) Score as Measured by Brief Fatigue Inventory(BFI) Fatigue Now Scale at End of Study | -1.1 Scores on a scale | Standard Deviation 2.95 |
| DA + Placebo | Change From Baseline in Quality of Life (QOL) Score as Measured by Brief Fatigue Inventory(BFI) Fatigue Now Scale at End of Study | -1.6 Scores on a scale | Standard Deviation 2.82 |
Comparison: With 176 evaluable participants per treatment arm, there would have been \>=80% power to detect a difference across two treatment arms of 33% of the standard deviation in participant QOL through t-test/Wilcoxon test, with a 2.5% type I error rate. A 10 points shift on a 0-100 point scale in QOL measures is generally considered clinically relevant and specifically important in the use of UNISCALE, BFI and FACT-An.p-value: 0.19t-test, 2 sided
Comparison: With 176 evaluable participants per treatment arm, there would have been \>=80% power to detect a difference across two treatment arms of 33% of the standard deviation in participant QOL through t-test/Wilcoxon test, with a 2.5% type I error rate. A 10 points shift on a 0-100 point scale in QOL measures is generally considered clinically relevant and specifically important in the use of UNISCALE, BFI and FACT-An.p-value: 0.17t-test, 2 sided
Secondary
Change From Baseline in Quality of Life (QOL) Score as Measured by Symptom Distress Scale (SDS) at End of Study
SDS Scale range: 0 (Worst), 100 (Best), ordinal. Change: score at 16 weeks minus score at baseline. A clinically significant result will be defined as a shift of 10 points on a 0-100 point transformed scale between the average QOL scores of the 3 variants of iron therapy.
Time frame: Baseline and 16 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DA + IV Iron | Change From Baseline in Quality of Life (QOL) Score as Measured by Symptom Distress Scale (SDS) at End of Study | 6.0 Scores on a scale | Standard Deviation 11.73 |
| DA + Oral Iron | Change From Baseline in Quality of Life (QOL) Score as Measured by Symptom Distress Scale (SDS) at End of Study | 3.5 Scores on a scale | Standard Deviation 11.54 |
| DA + Placebo | Change From Baseline in Quality of Life (QOL) Score as Measured by Symptom Distress Scale (SDS) at End of Study | 5.4 Scores on a scale | Standard Deviation 10.5 |
Comparison: With 176 evaluable participants per treatment arm, there would have been \>=80% power to detect a difference across two treatment arms of 33% of the standard deviation in participant QOL through t-test/Wilcoxon test, with a 2.5% type I error rate. A 10 points shift on a 0-100 point scale in QOL measures is generally considered clinically relevant and specifically important in the use of UNISCALE, BFI and FACT-An.p-value: 0.62t-test, 2 sided
Comparison: With 176 evaluable participants per treatment arm, there would have been \>=80% power to detect a difference across two treatment arms of 33% of the standard deviation in participant QOL through t-test/Wilcoxon test, with a 2.5% type I error rate. A 10 points shift on a 0-100 point scale in QOL measures is generally considered clinically relevant and specifically important in the use of UNISCALE, BFI and FACT-An.p-value: 0.3t-test, 2 sided
Secondary
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
FACT-AN Scale range: 0 (Worst) to 100 (Best), ordinal. Change: score at 16 weeks minus score at baseline. A clinically significant result will be defined as a shift of 10 points on a 0-100 point transformed scale between the average QOL scores of the 3 variants of iron therapy.
Time frame: Baseline and 16 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DA + IV Iron | 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 | 8.1 Scores on a scale | Standard Deviation 16.57 |
| DA + Oral Iron | 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 | 8.9 Scores on a scale | Standard Deviation 18.97 |
| DA + Placebo | 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 | 9.5 Scores on a scale | Standard Deviation 18.79 |
Comparison: With 176 evaluable participants per treatment arm, there would have been \>=80% power to detect a difference across two treatment arms of 33% of the standard deviation in participant QOL through t-test/Wilcoxon test, with a 2.5% type I error rate. A 10 points shift on a 0-100 point scale in QOL measures is generally considered clinically relevant and specifically important in the use of UNISCALE, BFI and FACT-An.p-value: 0.73t-test, 2 sided
Comparison: With 176 evaluable participants per treatment arm, there would have been \>=80% power to detect a difference across two treatment arms of 33% of the standard deviation in participant QOL through t-test/Wilcoxon test, with a 2.5% type I error rate. A 10 points shift on a 0-100 point scale in QOL measures is generally considered clinically relevant and specifically important in the use of UNISCALE, BFI and FACT-An.p-value: 0.83t-test, 2 sided
Secondary
C-reactive Protein (CRP) Level at Week 1, Week 7 and Week 16
Time frame: 1 Week, 7 Weeks and 16 Weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DA + IV Iron | C-reactive Protein (CRP) Level at Week 1, Week 7 and Week 16 | Week 7 | 28.6 mg/L | Standard Deviation 51.09 |
| DA + IV Iron | C-reactive Protein (CRP) Level at Week 1, Week 7 and Week 16 | Week 1 | 24.8 mg/L | Standard Deviation 38.12 |
| DA + IV Iron | C-reactive Protein (CRP) Level at Week 1, Week 7 and Week 16 | Week 16 | 25.6 mg/L | Standard Deviation 46.3 |
| DA + Oral Iron | C-reactive Protein (CRP) Level at Week 1, Week 7 and Week 16 | Week 7 | 16.6 mg/L | Standard Deviation 25.25 |
| DA + Oral Iron | C-reactive Protein (CRP) Level at Week 1, Week 7 and Week 16 | Week 1 | 25.4 mg/L | Standard Deviation 36.36 |
| DA + Oral Iron | C-reactive Protein (CRP) Level at Week 1, Week 7 and Week 16 | Week 16 | 16.7 mg/L | Standard Deviation 36.98 |
| DA + Placebo | C-reactive Protein (CRP) Level at Week 1, Week 7 and Week 16 | Week 1 | 31.6 mg/L | Standard Deviation 58.68 |
| DA + Placebo | C-reactive Protein (CRP) Level at Week 1, Week 7 and Week 16 | Week 16 | 21.2 mg/L | Standard Deviation 39.07 |
| DA + Placebo | C-reactive Protein (CRP) Level at Week 1, Week 7 and Week 16 | Week 7 | 27.0 mg/L | Standard Deviation 49.2 |
p-value: 0.3852Kruskal-Wallis
p-value: 0.0663Kruskal-Wallis
p-value: 0.322Kruskal-Wallis
Secondary
Ferritin Level at Baseline, Week 7 and Week 16
Time frame: Baseline, 7 weeks and 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DA + IV Iron | Ferritin Level at Baseline, Week 7 and Week 16 | Week 16 | 726.0 µg/L | Standard Deviation 1037.43 |
| DA + IV Iron | Ferritin Level at Baseline, Week 7 and Week 16 | Week 7 | 699.1 µg/L | Standard Deviation 645.31 |
| DA + IV Iron | Ferritin Level at Baseline, Week 7 and Week 16 | Baseline | 460.5 µg/L | Standard Deviation 526.99 |
| DA + Oral Iron | Ferritin Level at Baseline, Week 7 and Week 16 | Week 16 | 425.9 µg/L | Standard Deviation 717.43 |
| DA + Oral Iron | Ferritin Level at Baseline, Week 7 and Week 16 | Baseline | 479.5 µg/L | Standard Deviation 484.15 |
| DA + Oral Iron | Ferritin Level at Baseline, Week 7 and Week 16 | Week 7 | 420.6 µg/L | Standard Deviation 498.24 |
| DA + Placebo | Ferritin Level at Baseline, Week 7 and Week 16 | Week 7 | 478.4 µg/L | Standard Deviation 607.89 |
| DA + Placebo | Ferritin Level at Baseline, Week 7 and Week 16 | Baseline | 456.0 µg/L | Standard Deviation 479.27 |
| DA + Placebo | Ferritin Level at Baseline, Week 7 and Week 16 | Week 16 | 371.5 µg/L | Standard Deviation 479.87 |
p-value: 0.9022Kruskal-Wallis
p-value: 0.0002Kruskal-Wallis
p-value: 0.0022Kruskal-Wallis
Secondary
Incidence of Patients Receiving at Least One Red Blood Cell (RBC) Transfusions
Time frame: Week 1 to Week 16
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DA + IV Iron | Incidence of Patients Receiving at Least One Red Blood Cell (RBC) Transfusions | Yes | 20 Participants |
| DA + IV Iron | Incidence of Patients Receiving at Least One Red Blood Cell (RBC) Transfusions | No | 144 Participants |
| DA + Oral Iron | Incidence of Patients Receiving at Least One Red Blood Cell (RBC) Transfusions | No | 142 Participants |
| DA + Oral Iron | Incidence of Patients Receiving at Least One Red Blood Cell (RBC) Transfusions | Yes | 21 Participants |
| DA + Placebo | Incidence of Patients Receiving at Least One Red Blood Cell (RBC) Transfusions | Yes | 22 Participants |
| DA + Placebo | Incidence of Patients Receiving at Least One Red Blood Cell (RBC) Transfusions | No | 141 Participants |
Comparison: With 176 evaluable participants per treatment arm, there would have been \>=80% power to detect a difference across two treatment arms of 15% in the true percentage of patients that need transfusion was at least 30% in the superior group, with a 2.5% type I error rate.p-value: 0.725Fisher Exact
Comparison: With 176 evaluable participants per treatment arm, there would have been \>=80% power to detect a difference across two treatment arms of 15% in the true percentage of patients that need transfusion was at least 30% in the superior group, with a 2.5% type I error rate.p-value: 0.87Fisher Exact
Secondary
Mean Corpuscular Volume (MCV) Level at Baseline, Week 7 and Week 16
MCV is a measure of the average red blood cell volume.
Time frame: Baseline, 7 weeks and 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DA + IV Iron | Mean Corpuscular Volume (MCV) Level at Baseline, Week 7 and Week 16 | Week 7 | 93.0 fL | Standard Deviation 9.21 |
| DA + IV Iron | Mean Corpuscular Volume (MCV) Level at Baseline, Week 7 and Week 16 | Baseline | 90.0 fL | Standard Deviation 5.92 |
| DA + IV Iron | Mean Corpuscular Volume (MCV) Level at Baseline, Week 7 and Week 16 | Week 16 | 94.0 fL | Standard Deviation 11.37 |
| DA + Oral Iron | Mean Corpuscular Volume (MCV) Level at Baseline, Week 7 and Week 16 | Week 7 | 92.3 fL | Standard Deviation 9.7 |
| DA + Oral Iron | Mean Corpuscular Volume (MCV) Level at Baseline, Week 7 and Week 16 | Baseline | 88.5 fL | Standard Deviation 9.05 |
| DA + Oral Iron | Mean Corpuscular Volume (MCV) Level at Baseline, Week 7 and Week 16 | Week 16 | 94.4 fL | Standard Deviation 7.55 |
| DA + Placebo | Mean Corpuscular Volume (MCV) Level at Baseline, Week 7 and Week 16 | Baseline | 90.1 fL | Standard Deviation 8.19 |
| DA + Placebo | Mean Corpuscular Volume (MCV) Level at Baseline, Week 7 and Week 16 | Week 16 | 92.3 fL | Standard Deviation 9.31 |
| DA + Placebo | Mean Corpuscular Volume (MCV) Level at Baseline, Week 7 and Week 16 | Week 7 | 92.8 fL | Standard Deviation 8.56 |
p-value: 0.1137Kruskal-Wallis
p-value: 0.8042Kruskal-Wallis
p-value: 0.2016Kruskal-Wallis
Secondary
Mean Increment in Hemoglobin Level at Week 16
Value at 16 weeks minus value at baseline.
Time frame: Baseline and 16 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DA + IV Iron | Mean Increment in Hemoglobin Level at Week 16 | 2.1 g/dL | Standard Deviation 1.46 |
| DA + Oral Iron | Mean Increment in Hemoglobin Level at Week 16 | 2.0 g/dL | Standard Deviation 1.61 |
| DA + Placebo | Mean Increment in Hemoglobin Level at Week 16 | 1.7 g/dL | Standard Deviation 1.64 |
Comparison: With 176 evaluable participants per treatment arm, there would have been \>=80% power to detect a difference across two treatment arms of 33% of the standard deviation in average hemoglobin levels through two-sided alternative, with a 2.5% type I error rate.p-value: 0.1124t-test, 2 sided
Comparison: With 176 evaluable participants per treatment arm, there would have been \>=80% power to detect a difference across two treatment arms of 33% of the standard deviation in average hemoglobin levels through two-sided alternative, with a 2.5% type I error rate.p-value: 0.2051t-test, 2 sided
Secondary
Mean Increment in Hemoglobin Level at Week 7
Value at 7 weeks minus value at baseline.
Time frame: Baseline and 7 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DA + IV Iron | Mean Increment in Hemoglobin Level at Week 7 | 1.3 g/dL | Standard Deviation 1.35 |
| DA + Oral Iron | Mean Increment in Hemoglobin Level at Week 7 | 1.1 g/dL | Standard Deviation 1.37 |
| DA + Placebo | Mean Increment in Hemoglobin Level at Week 7 | 1.2 g/dL | Standard Deviation 1.35 |
Comparison: With 176 evaluable participants per treatment arm, there would have been \>=80% power to detect a difference across two treatment arms of 33% of the standard deviation in average hemoglobin levels through two-sided alternative, with a 2.5% type I error rate.p-value: 0.6639t-test, 2 sided
Comparison: With 176 evaluable participants per treatment arm, there would have been \>=80% power to detect a difference across two treatment arms of 33% of the standard deviation in average hemoglobin levels through two-sided alternative, with a 2.5% type I error rate.p-value: 0.566t-test, 2 sided
Secondary
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
Time frame: 16 Weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DA + IV Iron | 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 | 10 Percentage of Participants |
| DA + Oral Iron | 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 | 12 Percentage of Participants |
| DA + Placebo | 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 | 11 Percentage of Participants |
Secondary
Soluble Transferrin Receptor (sTfR)Level at Week 1, Week 7 and Week 16
Time frame: 1 week, 7 weeks and 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DA + IV Iron | Soluble Transferrin Receptor (sTfR)Level at Week 1, Week 7 and Week 16 | Week 7 | 6.1 mg/L | Standard Deviation 3.04 |
| DA + IV Iron | Soluble Transferrin Receptor (sTfR)Level at Week 1, Week 7 and Week 16 | Week 1 | 3.9 mg/L | Standard Deviation 2.14 |
| DA + IV Iron | Soluble Transferrin Receptor (sTfR)Level at Week 1, Week 7 and Week 16 | Week 16 | 5.1 mg/L | Standard Deviation 3.07 |
| DA + Oral Iron | Soluble Transferrin Receptor (sTfR)Level at Week 1, Week 7 and Week 16 | Week 7 | 6.2 mg/L | Standard Deviation 2.4 |
| DA + Oral Iron | Soluble Transferrin Receptor (sTfR)Level at Week 1, Week 7 and Week 16 | Week 1 | 4.0 mg/L | Standard Deviation 1.99 |
| DA + Oral Iron | Soluble Transferrin Receptor (sTfR)Level at Week 1, Week 7 and Week 16 | Week 16 | 5.2 mg/L | Standard Deviation 2.19 |
| DA + Placebo | Soluble Transferrin Receptor (sTfR)Level at Week 1, Week 7 and Week 16 | Week 1 | 4.5 mg/L | Standard Deviation 4.52 |
| DA + Placebo | Soluble Transferrin Receptor (sTfR)Level at Week 1, Week 7 and Week 16 | Week 16 | 5.6 mg/L | Standard Deviation 2.6 |
| DA + Placebo | Soluble Transferrin Receptor (sTfR)Level at Week 1, Week 7 and Week 16 | Week 7 | 7.1 mg/L | Standard Deviation 2.92 |
p-value: 0.1826Kruskal-Wallis
p-value: 0.0113Kruskal-Wallis
p-value: 0.3358Kruskal-Wallis
Secondary
Time to First Red Blood Cell (RBC) Transfusions
Time frame: 16 weeks
Population: Only 63 participants (20 DA + IV Iron, 21 DA + Oral Iron and 22 DA + Placebo) needed RBC transfusion during 16 weeks of treatment period. Thus, median of time to first RBC transfusion and 95 % confidence interval are not attainable.
Secondary
Time to Hematopoietic Response
Hematopoietic response was defined as 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.
Time frame: 16 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DA + IV Iron | Time to Hematopoietic Response | 43 Days |
| DA + Oral Iron | Time to Hematopoietic Response | 61 Days |
| DA + Placebo | Time to Hematopoietic Response | 50 Days |
p-value: 0.0648Log Rank
Secondary
Transferrin Saturation at Baseline, Week 7 and Week 16
Time frame: Baseline, 7 weeks and 16 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DA + IV Iron | Transferrin Saturation at Baseline, Week 7 and Week 16 | Week 7 | 25.6 Percentage Saturation | Standard Deviation 17.48 |
| DA + IV Iron | Transferrin Saturation at Baseline, Week 7 and Week 16 | Baseline | 22.5 Percentage Saturation | Standard Deviation 12.81 |
| DA + IV Iron | Transferrin Saturation at Baseline, Week 7 and Week 16 | Week 16 | 26.9 Percentage Saturation | Standard Deviation 14.16 |
| DA + Oral Iron | Transferrin Saturation at Baseline, Week 7 and Week 16 | Week 7 | 26.4 Percentage Saturation | Standard Deviation 23.56 |
| DA + Oral Iron | Transferrin Saturation at Baseline, Week 7 and Week 16 | Baseline | 19.6 Percentage Saturation | Standard Deviation 11.7 |
| DA + Oral Iron | Transferrin Saturation at Baseline, Week 7 and Week 16 | Week 16 | 27.6 Percentage Saturation | Standard Deviation 17.81 |
| DA + Placebo | Transferrin Saturation at Baseline, Week 7 and Week 16 | Baseline | 22.2 Percentage Saturation | Standard Deviation 13.36 |
| DA + Placebo | Transferrin Saturation at Baseline, Week 7 and Week 16 | Week 16 | 23.9 Percentage Saturation | Standard Deviation 15.54 |
| DA + Placebo | Transferrin Saturation at Baseline, Week 7 and Week 16 | Week 7 | 21.2 Percentage Saturation | Standard Deviation 13.12 |
p-value: 0.1139Kruskal-Wallis
p-value: 0.0424Kruskal-Wallis
p-value: 0.2025Kruskal-Wallis