Darbepoetin Alfa With or Without Iron in Treating Anemia Caused By Chemotherapy in Patients With Cancer - Full Text View

Sponsor:	Mayo Clinic
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Mayo Clinic
ClinicalTrials.gov Identifier:	NCT00661999

Purpose

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.

Condition	Intervention	Phase
Anemia Leukemia Lymphoma Lymphoproliferative Disorder Multiple Myeloma and Plasma Cell Neoplasm Precancerous Condition Unspecified Adult Solid Tumor, Protocol Specific	Biological: darbepoetin alfa Dietary Supplement: ferrous sulfate Drug: sodium ferric gluconate complex in sucrose Other: placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Supportive Care
Official Title:	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

Resource links provided by NLM:

Further study details as provided by Mayo Clinic:

Primary Outcome Measures:

Hematopoietic Response Rate Defined as the Number of Participants Who Exhibit a Hematopoietic Response [ Time Frame: 16 Weeks ] [ Designated as safety issue: No ]
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 Outcome Measures:

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 ] [ Designated as safety issue: No ]
Incidence of Patients Receiving at Least One Red Blood Cell (RBC) Transfusions [ Time Frame: Week 1 to Week 16 ] [ Designated as safety issue: No ]
Mean Increment in Hemoglobin Level at Week 7 [ Time Frame: Baseline and 7 weeks ] [ Designated as safety issue: No ]
Value at 7 weeks minus value at baseline.
Mean Increment in Hemoglobin Level at Week 16 [ Time Frame: Baseline and 16 weeks ] [ Designated as safety issue: No ]
Value at 16 weeks minus value at baseline.
Time to Hematopoietic Response [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
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 [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Overall QOL item score range: 0 (Worst) to 10 (Best), ordinal. Change: score at 16 weeks minus score at baseline.
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 ] [ Designated as safety issue: No ]
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.
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 ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline and 16 weeks ] [ Designated as safety issue: No ]
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.
C-reactive Protein (CRP) Level at Week 1, Week 7 and Week 16 [ Time Frame: 1 Week, 7 Weeks and 16 Weeks ] [ Designated as safety issue: No ]
Soluble Transferrin Receptor (sTfR)Level at Week 1, Week 7 and Week 16 [ Time Frame: 1 week, 7 weeks and 16 weeks ] [ Designated as safety issue: No ]
Ferritin Level at Baseline, Week 7 and Week 16 [ Time Frame: Baseline, 7 weeks and 16 weeks ] [ Designated as safety issue: No ]
Mean Corpuscular Volume (MCV) Level at Baseline, Week 7 and Week 16 [ Time Frame: Baseline, 7 weeks and 16 weeks ] [ Designated as safety issue: No ]
MCV is a measure of the average red blood cell volume.
Transferrin Saturation at Baseline, Week 7 and Week 16 [ Time Frame: Baseline, 7 weeks and 16 weeks ] [ Designated as safety issue: No ]

Enrollment:	502
Study Start Date:	January 2006
Study Completion Date:	March 2009
Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00661999

Locations

United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

Mayo Clinic

National Cancer Institute (NCI)

Investigators

Study Chair:	Charles L. Loprinzi, MD	Mayo Clinic
Principal Investigator:	Tom R. Fitch, M.D.	Mayo Clinic in Arizona

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Charles Lawrence Loprinzi, M.D., Mayo Clinic Cancer Center
ClinicalTrials.gov Identifier:	NCT00661999 History of Changes
Other Study ID Numbers:	CDR0000593480, P30CA015083, MC04CC, NCI-2009-01226, 1713-05
Study First Received:	April 18, 2008
Results First Received:	February 14, 2011
Last Updated:	May 13, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Mayo Clinic:

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

Additional relevant MeSH terms:

Anemia
Neoplasms
Disease
Leukemia
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Precancerous Conditions
Lymphoma, Large-Cell, Immunoblastic
Hematologic Diseases
Pathologic Processes
Neoplasms by Histologic Type

Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hemorrhagic Disorders
Ferric gluconate
Darbepoetin alfa
Ferric Compounds
Hematinics
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 09, 2012