Darbepoetin Alfa With or Without Iron in Treating Anemia Caused By Chemotherapy in Patients With Cancer

May 13, 2011 updated by: Mayo Clinic

A Phase III, Randomized Study of the Effects of Parenteral Iron, Oral Iron, or No Iron Supplementation on the Erythropoietic Response to Darbepoetin Alfa for Cancer Patients With Chemotherapy-Associated Anemia

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

502

Phase

  • Phase 3

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
    • Arizona
      • Scottsdale, Arizona, United States
        • Mayo Clinic in Arizona
    • 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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm I
Patients receive darbepoetin alfa subcutaneously and sodium ferric gluconate complex IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 15 weeks in the absence of unacceptable toxicity.
Biological: darbepoetin alfa
Given by injection
Drug: sodium ferric gluconate complex in sucrose
Given by IV
Experimental: Arm II
Patients receive darbepoetin alfa 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.
Biological: darbepoetin alfa
Given by injection
Dietary supplement: ferrous sulfate
Given by mouth
Experimental: Arm III
Patients receive darbepoetin alfa 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.
Biological: darbepoetin alfa
Given by injection
Other: placebo
Given by mouth

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hematopoietic Response Rate Defined as the Number of Participants Who Exhibit a Hematopoietic Response
Time Frame: 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.
16 Weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
16 Weeks
Incidence of Patients Receiving at Least One Red Blood Cell (RBC) Transfusions
Time Frame: Week 1 to Week 16
Week 1 to Week 16
Mean Increment in Hemoglobin Level at Week 7
Time Frame: Baseline and 7 weeks
Value at 7 weeks minus value at baseline.
Baseline and 7 weeks
Mean Increment in Hemoglobin Level at Week 16
Time Frame: Baseline and 16 weeks
Value at 16 weeks minus value at baseline.
Baseline and 16 weeks
Time to Hematopoietic Response
Time Frame: 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.
16 weeks
Time to First Red Blood Cell (RBC) Transfusions
Time Frame: 16 weeks
16 weeks
Change From Baseline in Overall Quality of Life (QOL) Score as Measured by the Linear Analogue Self Assessment (LASA)
Time Frame: Baseline and 16 weeks
Overall QOL item score range: 0 (Worst) to 10 (Best), ordinal. Change: score at 16 weeks minus score at baseline.
Baseline and 16 weeks
Change From Baseline in Quality of Life (QOL) Score as Measured by Symptom Distress Scale (SDS) at End of Study
Time Frame: 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.
Baseline 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
Time Frame: Baseline and 16 weeks
Fatigue Now Scale range: 0 (No Fatigue) to 10 (Worst), ordinal. Change: score at 16 weeks minus score at baseline.
Baseline and 16 weeks
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
Time Frame: 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.
Baseline and 16 weeks
C-reactive Protein (CRP) Level at Week 1, Week 7 and Week 16
Time Frame: 1 Week, 7 Weeks and 16 Weeks
1 Week, 7 Weeks and 16 Weeks
Soluble Transferrin Receptor (sTfR)Level at Week 1, Week 7 and Week 16
Time Frame: 1 week, 7 weeks and 16 weeks
1 week, 7 weeks and 16 weeks
Ferritin Level at Baseline, Week 7 and Week 16
Time Frame: Baseline, 7 weeks and 16 weeks
Baseline, 7 weeks and 16 weeks
Mean Corpuscular Volume (MCV) Level at Baseline, Week 7 and Week 16
Time Frame: Baseline, 7 weeks and 16 weeks
MCV is a measure of the average red blood cell volume.
Baseline, 7 weeks and 16 weeks
Transferrin Saturation at Baseline, Week 7 and Week 16
Time Frame: Baseline, 7 weeks and 16 weeks
Baseline, 7 weeks and 16 weeks

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

  • Principal Investigator: Tom R. Fitch, 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

January 1, 2006

Primary Completion (Actual)

March 1, 2009

Study Completion (Actual)

March 1, 2009

Study Registration Dates

First Submitted

April 18, 2008

First Submitted That Met QC Criteria

April 18, 2008

First Posted (Estimate)

April 21, 2008

Study Record Updates

Last Update Posted (Estimate)

May 17, 2011

Last Update Submitted That Met QC Criteria

May 13, 2011

Last Verified

May 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000593480
  • P30CA015083 (U.S. NIH Grant/Contract)
  • MC04CC (Other Identifier: Mayo Clinic Cancer Center)
  • NCI-2009-01226 (Registry Identifier: NCI-CTRP)
  • 1713-05 (Other Identifier: Mayo Clinic IRB)

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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