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