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
18 Years
N/A
Both
Anemia, Leukemia, Lymphoma, Lymphoproliferative Disorder, Multiple Myeloma and Plasma Cell Neoplasm, Precancerous Condition, Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
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
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Supportive Care
Outcome Measure:
Hematopoietic Response Rate Defined as the Number of Participants Who Exhibit a Hematopoietic Response
Outcome Description:
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.
Outcome Time Frame:
16 Weeks
Safety Issue:
No
Principal Investigator
Charles L. Loprinzi, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Mayo Clinic
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000593480
NCT ID:
NCT00661999
Start Date:
January 2006
Completion Date:
March 2009
Related Keywords:
- Anemia
- Leukemia
- Lymphoma
- Lymphoproliferative Disorder
- Multiple Myeloma and Plasma Cell Neoplasm
- Precancerous Condition
- Unspecified Adult Solid Tumor, Protocol Specific
- 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
- Anemia
- Neoplasms
- Leukemia
- Lymphoma
- Lymphoma, Non-Hodgkin
- Lymphoproliferative Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
- Precancerous Conditions
- Lymphoma, Large-Cell, Immunoblastic
Name | Location |
|---|---|
| Mayo Clinic | Rochester, Minnesota 55905 |
| Mayo Clinic in Arizona | Scottsdale, Arizona 85259-5404 |
