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

December 19, 2016 updated by: Mayo Clinic

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

239

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Percentage of Participants Who Exhibit a Hematopoietic Response
Time Frame: 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
20 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mayo Clinic

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Charles L. Loprinzi, M.D., Mayo Clinic

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2007

Primary Completion (Actual)

June 1, 2009

Study Completion (Actual)

June 1, 2009

Study Registration Dates

First Submitted

December 27, 2006

First Submitted That Met QC Criteria

December 27, 2006

First Posted (Estimate)

December 28, 2006

Study Record Updates

Last Update Posted (Actual)

February 10, 2017

Last Update Submitted That Met QC Criteria

December 19, 2016

Last Verified

September 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000522677
  • P30CA015083 (U.S. NIH Grant/Contract)
  • RC05CB (Other Identifier: Mayo Clinic Cancer Center & MCCRC)
  • 06-002991 (Other Identifier: Mayo Clinic IRB)
  • EPOANE3015 (Other Identifier: Centocor protocol)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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