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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


Phase 3
18 Years
N/A
Not Enrolling
Both
Anemia, Leukemia, Lymphoma, Lymphoproliferative Disorder, Multiple Myeloma and Plasma Cell Neoplasm, Precancerous Condition, Unspecified Adult Solid Tumor, Protocol Specific

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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 ClinicRochester, Minnesota  55905
Mayo Clinic in ArizonaScottsdale, Arizona  85259-5404