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:	National Cancer Institute (NCI)
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 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/Nonmalignant 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:	Supportive Care, Randomized, Double-Blind, Placebo Control
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:

Genetics Home Reference related topics: aceruloplasminemia hemophilia transthyretin amyloidosis

MedlinePlus related topics: Anemia Cancer Dietary Supplements Fungal Infections Hodgkin Disease Leukemia, Adult Acute Leukemia, Adult Chronic Lymphoma Multiple Myeloma

Drug Information available for: Sucrose Sodium ferric gluconate complex Darbepoetin alfa Gluconic acid D-Gluconic acid, monosodium salt Manganese gluconate Ferrous sulfate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Proportion of patients who exhibit a hematopoietic response [ Designated as safety issue: No ]

Secondary Outcome Measures:

Percentage of patients maintaining an average hemoglobin level within the NCCN range (11-13 g/dL) through week 16, once achieving a hemoglobin of ≥ 11 g/dL [ Designated as safety issue: No ]
Incidence of patients receiving at least one RBC transfusion from week 1 to week 16 [ Designated as safety issue: No ]
Comparison of mean hemoglobin increment at weeks 7 and 16 with the baseline hemoglobin value [ Designated as safety issue: No ]
Time to hematopoietic response [ Designated as safety issue: No ]
Time to first RBC transfusion [ Designated as safety issue: No ]
Overall quality of life as measured by the UNISCALE, LASA, SDS, BFI, and FACT-An questionnaires [ Designated as safety issue: No ]
Effect of CRP, serum hepcidin levels, sTfR/log ferritin ratio, ferritin, MCV, red cell distribution width, and transferrin saturation on response rates [ Designated as safety issue: No ]

Estimated Enrollment:	582
Study Start Date:	January 2006
Estimated Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Experimental 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
Arm II: Experimental 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
Arm III: Experimental 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 ASCO/ASH and 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 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 CRP and serum hepcidin levels or low 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 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, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

Mayo Clinic

National Cancer Institute (NCI)

Investigators

Study Chair:	David P. Steensma, MD	Mayo Clinic
Investigator:	Charles L. Loprinzi, MD	Mayo Clinic

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:	Mayo Clinic Cancer Center ( David P. Steensma )
Study ID Numbers:	CDR0000593480, MAYO-MC04CC
Study First Received:	April 18, 2008
Last Updated:	May 9, 2009
ClinicalTrials.gov Identifier:	NCT00661999 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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:

Ferric Compounds
Precancerous Conditions
Blood Protein Disorders
Hematologic Agents
Paraproteinemias
Hemostatic Disorders
Leukemia
Pathologic Processes
Hemorrhagic Disorders
Therapeutic Uses
Lymphoma, Large-Cell, Immunoblastic
Cardiovascular Diseases
Lymphoma
Disease
Neoplasms by Histologic Type

Immunoproliferative Disorders
Immune System Diseases
Hematinics
Hematologic Diseases
Anemia
Vascular Diseases
Darbepoetin alfa
Pharmacologic Actions
Multiple Myeloma
Lymphatic Diseases
Neoplasms
Ferric gluconate
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin
Neoplasms, Plasma Cell

ClinicalTrials.gov processed this record on November 09, 2009