Epoetin Alfa or Darbepoetin Alfa in Treating Patients With Anemia Caused by Chemotherapy

Study Overview
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Brief Summary
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RATIONALE: Epoetin alfa and darbepoetin alfa may cause the body to make more red blood cells. They are used to treat anemia caused by chemotherapy in patients with cancer. PURPOSE: This randomized clinical trial is studying four different schedules of epoetin alfa or darbepoetin alfa to compare how well they work in treating patients with anemia caused by chemotherapy.

Detailed Description
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OBJECTIVES: Primary Compare the relative efficacy of four different erythropoietic agent dosing schedules comprising epoetin alfa or darbepoetin alfa, in terms of the proportion of patients with chemotherapy-associated anemia who achieve a weekly and overall hematopoietic response. Secondary Compare the effect of these regimens on the mean hemoglobin increment measured weekly from baseline to 15 weeks in patients with a baseline hemoglobin of less than or equal to 10.5 g/dL. Compare the time required to achieve hemoglobin levels within the goal range 11.0-12.0 g/dL in patients treated with these regimens. Compare the effect of these regimens on the proportion of patients requiring red blood cell transfusions and on the number of transfusions required. Compare the weekly change in hemoglobin in patients treated with these regimens. Compare the need for dose reduction in patients treated with these regimens. Compare the adverse event profiles of these regimens in these patients. Compare quality of life of patients treated with these regimens. OUTLINE: This is a randomized, unblinded, pilot study. Patients are stratified according to severity of anemia (mild [hemoglobin ≥ 9.5 g/dL] vs severe [hemoglobin < 9.5 g/dL]), platinum-containing regimen (yes vs no), and tumor type (nonmyeloid hematologic malignancy vs solid tumor). Patients are randomized to 1 of 4 treatment arms. Arm I: Patients receive epoetin alfa subcutaneously (SC) on day 1. Treatment repeats weekly for up to 15 courses in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive epoetin alfa SC on day 1 (at a higher dose than in arm I). Treatment repeats every 3 weeks for up to 5 courses in the absence of disease progression or unacceptable toxicity. Arm III: Patients receive epoetin alfa SC on day 1 (at a higher dose than in arm II). Treatment repeats every 3 weeks for up to 5 courses in the absence of disease progression or unacceptable toxicity. Arm IV: Patients receive darbepoetin alfa SC on day 1. Treatment repeats every 3 weeks for up to 5 courses in the absence of disease progression or unacceptable toxicity. Hemoglobin levels are monitored throughout the study on a weekly basis and before each drug dose is administered. Drug dosing is adjusted (e.g., held, reduced, resumed at a lower dose) as needed to maintain hemoglobin values within the desired ranges. Quality of life is assessed at baseline and at weeks 4, 7, 10, 13, and 16. After completion of study treatment, patients are followed at 30 days. PROJECTED ACCRUAL: A total of 320 patients will be accrued for this study.

Official Title
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RC05CB A Pilot, Randomized Comparison of Standard Weekly Epoetin Alfa to Every-3-Week-Epoetin Alfa and Every 3-Week Darbepoetin Alfa

Conditions
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Anemia, Leukemia, Lymphoma, Lymphoproliferative Disorder, Multiple Myeloma and Plasma Cell Neoplasm, Precancerous Condition, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: darbepoetin alfa
* Drug: epoetin alfa
* Procedure: fatigue assessment and management
* Procedure: quality-of-life assessment


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of solid tumor or nonmyeloid hematologic malignancy (e.g., plasma cell dyscrasia or lymphoproliferative disorder) No nonmelanomatous skin cancer Hemoglobin ≤ 10.5 g/dL Ferritin > 20 ng/mL (i.e., not obviously iron deficient) Planning to receive ≥ 12 weeks of anticancer chemotherapy Biological therapy (e.g., hypomethylating agents, monoclonal antibodies, or small molecule pathway inhibitors) with an individual or cumulative regimen incidence of grade 3 or 4 anemia > 10% is considered chemotherapy for purposes of this study No known anemia secondary to any of the following: Cyanocobalamin (vitamin B_12) or folic acid deficiency Gastrointestinal bleeding within the past 2 weeks Hemolysis Myelodysplastic syndromes, myeloproliferative disorders, or acute myeloid leukemia No primary hematologic disorder causing chronic moderate to severe anemia (e.g., congenital dyserythropoietic anemia, homozygous hemoglobin S disease or compound heterozygous sickling states, or thalassemia major) Carriers of these disease states allowed provided they are not anemic prior to cancer diagnosis PATIENT CHARACTERISTICS: ECOG performance status 0-2 Life expectancy ≥ 6 months Not pregnant or nursing No delivery of a baby of ≥ 18 weeks estimated gestational age within the past 3 months (90 days) Negative pregnancy test Fertile patients must use effective contraception Weight > 40.0 kg and < 150.0 kg No known hypersensitivity to epoetin alfa, darbepoetin alfa, mammalian-cell derived products, or human albumin No uncontrolled hypertension, defined as systolic blood pressure (BP) ≥ 180 mm Hg and/or diastolic BP ≥ 100 mm Hg, despite medical therapy No pulmonary emboli and/or deep vein thrombosis within the past 12 months Patients actively receiving warfarin for a minimum of 4 weeks are exempted from this requirement Prior superficial thrombophlebitis allowed No cerebrovascular accident, ischemic stroke, acute coronary syndrome (e.g., unstable angina or Q-wave or non-Q wave myocardial infarction), or other arterial or venous thrombotic events within the past 6 months No history of chronic hypercoagulable disorders (e.g., activated protein C resistance, anti-cardiolipin disorder, protein C deficiency, or protein S deficiency) Patients receiving anticoagulation therapy (warfarin or acetylsalicyclic acid [aspirin] at a dose of ≥ 325 mg/day) for these conditions are eligible provided therapy is continued during the study period History of previously treated seizures allowed provided the patient has been seizure-free for a minimum of 3 months PRIOR CONCURRENT THERAPY: See Disease Characteristics More than 1 year since prior peripheral blood stem cell, bone marrow, or cord blood transplantation More than 14 days since prior red blood cell transfusion More than 14 days since prior major surgery, including, but not limited to, any of the following: Amputation Invasion of a body cavity or of the central nervous system using a scalpel, saw, or laser cutting tool Resection of a body part (or parts), whether solid or liquid tissue or both, that includes ≥ 1% of a patient's preoperative weight The following are not considered major surgery: Diagnostic/therapeutic thoracentesis or paracentesis Diagnostic skin biopsy Digit or fingernail/thumbnail resection or laceration repair under local anesthesia Diagnostic fat aspiration Otic irrigation to remove cerumen impaction Tympanocentesis Uncomplicated dental extraction Uncomplicated tonsillectomy Laser corneal remodeling for refraction purposes Cosmetic or therapeutic eyelid surgery Bone marrow aspiration and biopsy More than 10 weeks since prior darbepoetin alfa, epoetin alfa, or any investigational form of erythropoietin (e.g., gene-activated erythropoietin or novel erythropoiesis stimulating protein) No planned stem cell transplantation within the next 4 months (18 weeks)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Epoetin alfa - 40000 units<br>40,000 Units | Drug: darbepoetin alfa<br> <br> Drug: epoetin alfa<br> <br> Procedure: fatigue assessment and management<br> <br> Procedure: quality-of-life assessment<br> <br> |
| Experimental: Epoetin alfa - 80000 units<br>80,000 Units | Drug: darbepoetin alfa<br> <br> Drug: epoetin alfa<br> <br> Procedure: fatigue assessment and management<br> <br> Procedure: quality-of-life assessment<br> <br> |
| Experimental: Epoetin alfa - 120000 Units<br>120,000 Units | Drug: darbepoetin alfa<br> <br> Drug: epoetin alfa<br> <br> Procedure: fatigue assessment and management<br> <br> Procedure: quality-of-life assessment<br> <br> |
| Experimental: Darbepoetin alfa***<br>500 mcg | Drug: darbepoetin alfa<br> <br> Drug: epoetin alfa<br> <br> Procedure: fatigue assessment and management<br> <br> Procedure: quality-of-life assessment<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Participants Who Exhibit a Hematopoietic Response | A hematopoietic response was defined as Hb rise >2 g/dL from baseline or achieving Hb ≥ 11.5 g/dL, whichever occurs first, in the absence of RBC transfusions within 14 days of measurement) during the treatment period | 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weekly Change in Hemoglobin Levels | To compare the effects of the 3 different epoetin alfa dosing schedules and an every-3-weeks darbepoetin alfa schedule | Baseline and Week 4, 7, 10, 13, 16 | 
| Time Required to Achieve Hemoglobin Levels >= 11.5 g/dL | To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa schedule | 16 weeks | 
| Mean Hemoglobin Change From Week 1 to Week 16 | To compare the effects of the 3 different epoetin alfa dosing schedules and an every-3-weeks darbepoetin alfa schedule. The positive numbers represent hemoglobin increases and negative numbers represent hemoglobin decreases. | Week 1 and Week 16 | 
| The Percentage of Participants Requiring Red Blood Cell (RBC) Transfusions | To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa schedule | 16 weeks | 
| The Total RBC Transfusion Needed | To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa schedule | 16 weeks | 
| The Percentage of Participants With Dose Omitted Due to Hematologic Reason | To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa schedule | 16 Weeks | 
| The Percentage of Participants Reported Grade 3 or 4 Adverse Events | To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa schedule. Adverse events were measured by Common Terminology Criteria for Adverse Events (CTCAE) v3.0. | 16 weeks | 
| Quality of Life as Measured by Functional Assessment of Cancer Therapy Scales for Anemia (FACT-AN) Over All Follow-up Evaluations | To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa schedule. FACT-AN consist of Fatigue concerns subscale and non-fatigue concerns subscale. FACT Total Anemia score was calculated by adding the two subscales scores and transformed into 0-100 scale. FACT Total Anemia, Fatigue concerns scale and Non-Fatigue concerns scale are all ranges: 0 (Worst QOL) to 100 (Best QOL). Average scores across all time points for each subscale and total scale were calculated. | Weeks 4, 7, 10, 13 and 16 | 
| Quality of Life as Measured by Linear Analogue Self Assessment Over All Follow-up Evaluation | To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa schedule. Linear Analogue Self Assessment (LASA) consists of 10 single-item numeric analogue scales on a scale of 0 to 10. Higher scores indicate better quality of life (QOL) on overall QOL, mental, physical, emotional spiritual QOL and Social activity; and constant pain, highest pain severity, level of fatigue and anxiety. Average scores across all time points for each item were calculated. | Weeks 4, 7, 10, 13 and 16 | 
| Quality of Life as Measured by Brief Fatigue Inventory Overall All Follow-up Evaluations | To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa schedule. Brief Fatigue Inventory (BFI) consist of 3 single-item numeric analogue scales on a scale of 0 to 10; and an interference scale formed by 6 single-item numeric scales on a scale of 0 to 10. Higher scores indicate fatigue as bad as you can imagine for fatigue now, usual fatigue and worse fatigue; and completely interferes for BFI interference. Average scores across all time points for fatigue now, usual fatigue, worst fatigue and BFI interference subscale were calculated. | Weeks 4, 7, 10, 13 and 16 | 
| Quality of Life as Measured by Symptom Distress Scale (SDS) Over All Follow-up Evaluations | To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa schedule. SDS Scale range: 1 (No Symptom), 5 (Worst Symptom). Average scores across all time points for each item were calculated. | Weeks 4, 7, 10, 13 and 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific, extramedullary plasmacytoma, isolated plasmacytoma of bone, refractory multiple myeloma, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, 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, AIDS-related peripheral/systemic lymphoma, AIDS-related primary CNS 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, 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 grade III lymphomatoid granulomatosis, 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, monoclonal gammopathy of undetermined significance, primary systemic amyloidosis, T-cell large granular lymphocyte leukemia, acute undifferentiated leukemia, mast cell leukemia, adult nasal type extranodal NK/T-cell lymphoma, untreated hairy cell leukemia