darbepoetin alfa with or without iron in treating anemia caused by chemotherapy in patients with cancer

Conditions: Anemia; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Precancerous Condition; Unspecified Adult Solid Tumor, Protocol Specific

Summary: 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.

Eligibility 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

Keywords: 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 stage iii adult hodgkin lymphoma stage iv adult hodgkin lymphoma recurrent adult hodgkin lymphoma recurrent adult grade iii lymphomatoid granulomatosis stage i adult burkitt lymphoma stage iii adult burkitt lymphoma stage iv adult burkitt lymphoma noncontiguous stage ii adult burkitt lymphoma noncontiguous stage ii adult diffuse large cell lymphoma noncontiguous stage ii adult diffuse mixed cell lymphoma noncontiguous stage ii adult diffuse small cleaved cell lymphoma noncontiguous stage ii adult immunoblastic large cell lymphoma noncontiguous stage ii adult lymphoblastic lymphoma noncontiguous stage ii grade 1 follicular lymphoma noncontiguous stage ii grade 2 follicular lymphoma noncontiguous stage ii grade 3 follicular lymphoma noncontiguous stage ii mantle cell lymphoma noncontiguous stage ii marginal zone lymphoma noncontiguous stage ii small lymphocytic lymphoma contiguous stage ii adult burkitt lymphoma contiguous stage ii adult diffuse large cell lymphoma contiguous stage ii adult diffuse mixed cell lymphoma contiguous stage ii adult diffuse small cleaved cell lymphoma contiguous stage ii adult immunoblastic large cell lymphoma contiguous stage ii adult lymphoblastic lymphoma contiguous stage ii grade 1 follicular lymphoma contiguous stage ii grade 2 follicular lymphoma contiguous stage ii grade 3 follicular lymphoma contiguous stage ii mantle cell lymphoma contiguous stage ii marginal zone lymphoma contiguous stage ii small lymphocytic lymphoma stage i adult diffuse large cell lymphoma stage i adult diffuse mixed cell lymphoma stage i adult diffuse small cleaved cell lymphoma stage iii adult diffuse large cell lymphoma stage iii adult diffuse mixed cell lymphoma stage iii adult diffuse small cleaved cell lymphoma stage iv adult diffuse large cell lymphoma stage iv adult diffuse mixed cell lymphoma stage iv adult diffuse small cleaved cell lymphoma stage i adult immunoblastic large cell lymphoma stage iii adult immunoblastic large cell lymphoma stage iv adult immunoblastic large cell lymphoma stage i adult lymphoblastic lymphoma stage iii adult lymphoblastic lymphoma stage iv adult lymphoblastic lymphoma stage i grade 1 follicular lymphoma stage i grade 2 follicular lymphoma stage i grade 3 follicular lymphoma stage iii grade 1 follicular lymphoma stage iii grade 2 follicular lymphoma stage iii grade 3 follicular lymphoma stage iv grade 1 follicular lymphoma stage iv grade 2 follicular lymphoma stage iv grade 3 follicular lymphoma stage i mantle cell lymphoma stage i marginal zone lymphoma stage iii mantle cell lymphoma stage iii marginal zone lymphoma stage iv mantle cell lymphoma stage iv marginal zone lymphoma stage i small lymphocytic lymphoma stage iii small lymphocytic lymphoma stage iv small lymphocytic lymphoma extranodal marginal zone b-cell lymphoma of mucosa-associated lymphoid tissue nodal marginal zone b-cell lymphoma splenic marginal zone lymphoma recurrent adult burkitt lymphoma recurrent adult diffuse large cell lymphoma recurrent adult diffuse mixed cell lymphoma recurrent adult diffuse small cleaved cell lymphoma recurrent adult immunoblastic large cell lymphoma recurrent adult lymphoblastic lymphoma recurrent grade 1 follicular lymphoma recurrent grade 2 follicular lymphoma recurrent grade 3 follicular lymphoma recurrent mantle cell lymphoma recurrent marginal zone lymphoma recurrent small lymphocytic lymphoma adult acute lymphoblastic leukemia in remission recurrent adult acute lymphoblastic leukemia untreated adult acute lymphoblastic leukemia stage i chronic lymphocytic leukemia stage ii chronic lymphocytic leukemia stage iii chronic lymphocytic leukemia stage iv chronic lymphocytic leukemia refractory chronic lymphocytic leukemia refractory hairy cell leukemia progressive hairy cell leukemia, initial treatment prolymphocytic leukemia anemia t-cell large granular lymphocyte leukemia acute undifferentiated leukemia mast cell leukemia adult nasal type extranodal nk/t-cell lymphoma untreated hairy cell leukemia