Clinical trial NCT00661999: Darbepoetin Alfa With or Without Iron in Treating Anemia Caused By Chemotherapy in Patients With Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anemia
Leukemia
Lymphoma
Lymphoproliferative Disorder
Multiple Myeloma and Plasma Cell Neoplasm
Precancerous Condition
Unspecified Adult Solid Tumor, Protocol Specific
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
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-04-21
Enrollment: 502
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief 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.

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 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

Primary outcomes:
measure: Hematopoietic Response Rate Defined as the Number of Participants Who Exhibit a Hematopoietic Response
timeFrame: 16 Weeks
Secondary outcomes:
measure: Percentage of Patients Maintaining an Average Hemoglobin Level Within the National Comprehensive Cancer Network (NCCN) Range (11-13 g/dL) Through Week 16, Once Achieving a Hemoglobin of ≥ 11 g/dL
timeFrame: 16 Weeks
measure: Incidence of Patients Receiving at Least One Red Blood Cell (RBC) Transfusions
timeFrame: Week 1 to Week 16
measure: Mean Increment in Hemoglobin Level at Week 7
timeFrame: Baseline and 7 weeks
measure: Mean Increment in Hemoglobin Level at Week 16
timeFrame: Baseline and 16 weeks
measure: Time to Hematopoietic Response
timeFrame: 16 weeks
measure: Time to First Red Blood Cell (RBC) Transfusions
timeFrame: 16 weeks
measure: Change From Baseline in Overall Quality of Life (QOL) Score as Measured by the Linear Analogue Self Assessment (LASA)
timeFrame: Baseline and 16 weeks
measure: Change From Baseline in Quality of Life (QOL) Score as Measured by Symptom Distress Scale (SDS) at End of Study
timeFrame: Baseline and 16 weeks
measure: Change From Baseline in Quality of Life (QOL) Score as Measured by Brief Fatigue Inventory(BFI) Fatigue Now Scale at End of Study
timeFrame: Baseline and 16 weeks
measure: Change From Baseline in Quality of Life (QOL) Score as Measured by The Functional Assessment of Cancer Therapy-Anemia (FACT-An) at End of Study
timeFrame: Baseline and 16 weeks
measure: C-reactive Protein (CRP) Level at Week 1, Week 7 and Week 16
timeFrame: 1 Week, 7 Weeks and 16 Weeks
measure: Soluble Transferrin Receptor (sTfR)Level at Week 1, Week 7 and Week 16
timeFrame: 1 week, 7 weeks and 16 weeks
measure: Ferritin Level at Baseline, Week 7 and Week 16
timeFrame: Baseline, 7 weeks and 16 weeks
measure: Mean Corpuscular Volume (MCV) Level at Baseline, Week 7 and Week 16
timeFrame: Baseline, 7 weeks and 16 weeks
measure: Transferrin Saturation at Baseline, Week 7 and Week 16
timeFrame: Baseline, 7 weeks and 16 weeks
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic in Arizona
state: Arizona
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Charles L. Loprinzi, MD
role: STUDY_CHAIR
affiliation: Mayo Clinic
name: Tom R. Fitch, M.D.
role: PRINCIPAL_INVESTIGATOR
References: