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

Phase 2

Completed

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

Interventions: Drug: darbepoetin alfa
Drug: epoetin alfa
Procedure: fatigue assessment and management
Procedure: quality-of-life assessment

Registration Number: NCT00416624

Lead Sponsor: Mayo Clinic

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 239

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Epoetin alfa - 40000 units	epoetin alfa	40,000 Units
Epoetin alfa - 40000 units	fatigue assessment and management	40,000 Units
Epoetin alfa - 80000 units	fatigue assessment and management	80,000 Units
Epoetin alfa - 40000 units	darbepoetin alfa	40,000 Units
Darbepoetin alfa***	epoetin alfa	500 mcg
Epoetin alfa - 80000 units	quality-of-life assessment	80,000 Units
Darbepoetin alfa***	fatigue assessment and management	500 mcg
Epoetin alfa - 40000 units	quality-of-life assessment	40,000 Units
Epoetin alfa - 120000 Units	quality-of-life assessment	120,000 Units
Darbepoetin alfa***	quality-of-life assessment	500 mcg
Epoetin alfa - 120000 Units	epoetin alfa	120,000 Units
Epoetin alfa - 120000 Units	fatigue assessment and management	120,000 Units
Epoetin alfa - 80000 units	epoetin alfa	80,000 Units
Epoetin alfa - 80000 units	darbepoetin alfa	80,000 Units
Epoetin alfa - 120000 Units	darbepoetin alfa	120,000 Units
Darbepoetin alfa***	darbepoetin alfa	500 mcg

Primary Outcome Measures

Name	Time	Method
The Percentage of Participants Who Exhibit a Hematopoietic Response	20 weeks	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

Secondary Outcome Measures

Name	Time	Method
Weekly Change in Hemoglobin Levels	Baseline and Week 4, 7, 10, 13, 16	To compare the effects of the 3 different epoetin alfa dosing schedules and an every-3-weeks darbepoetin alfa schedule
Time Required to Achieve Hemoglobin Levels >= 11.5 g/dL	16 weeks	To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa schedule
Mean Hemoglobin Change From Week 1 to Week 16	Week 1 and 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.
The Total RBC Transfusion Needed	16 weeks	To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa schedule
The Percentage of Participants Reported Grade 3 or 4 Adverse Events	16 weeks	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.
The Percentage of Participants Requiring Red Blood Cell (RBC) Transfusions	16 weeks	To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa schedule
The Percentage of Participants With Dose Omitted Due to Hematologic Reason	16 Weeks	To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa schedule
Quality of Life as Measured by Symptom Distress Scale (SDS) Over All Follow-up Evaluations	Weeks 4, 7, 10, 13 and 16	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.
Quality of Life as Measured by Functional Assessment of Cancer Therapy Scales for Anemia (FACT-AN) Over All Follow-up Evaluations	Weeks 4, 7, 10, 13 and 16	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.
Quality of Life as Measured by Linear Analogue Self Assessment Over All Follow-up Evaluation	Weeks 4, 7, 10, 13 and 16	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.
Quality of Life as Measured by Brief Fatigue Inventory Overall All Follow-up Evaluations	Weeks 4, 7, 10, 13 and 16	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.