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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00661999
• Other study ID #: CDR0000593480
• Secondary ID: P30CA015083MC04C
• Status: Completed
• Phase: Phase 3
• First received: April 18, 2008
• Last updated: May 13, 2011
• Start date: January 2006
• Est. completion date: March 2009

Study information

• Verified date: May 2011
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 502
• Est. completion date: March 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Anemia
• Leukemia
• Lymphoma
• Lymphoproliferative Disorder
• Lymphoproliferative Disorders
• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Neoplasms, Plasma Cell
• Plasmacytoma
• Precancerous Condition
• Precancerous Conditions
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Biological:
• darbepoetin alfa
Given by injection

Dietary Supplement:
• ferrous sulfate
Given by mouth

Drug:
• sodium ferric gluconate complex in sucrose
Given by IV

Other:
• placebo
Given by mouth

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota
United States	Mayo Clinic in Arizona	Scottsdale	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hematopoietic Response Rate Defined as the Number of Participants Who Exhibit a Hematopoietic Response	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.	16 Weeks	No
Secondary	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		16 Weeks	No
Secondary	Incidence of Patients Receiving at Least One Red Blood Cell (RBC) Transfusions		Week 1 to Week 16	No
Secondary	Mean Increment in Hemoglobin Level at Week 7	Value at 7 weeks minus value at baseline.	Baseline and 7 weeks	No
Secondary	Mean Increment in Hemoglobin Level at Week 16	Value at 16 weeks minus value at baseline.	Baseline and 16 weeks	No
Secondary	Time to Hematopoietic Response	Hematopoietic response was defined as 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.	16 weeks	No
Secondary	Time to First Red Blood Cell (RBC) Transfusions		16 weeks	No
Secondary	Change From Baseline in Overall Quality of Life (QOL) Score as Measured by the Linear Analogue Self Assessment (LASA)	Overall QOL item score range: 0 (Worst) to 10 (Best), ordinal. Change: score at 16 weeks minus score at baseline.	Baseline and 16 weeks	No
Secondary	Change From Baseline in Quality of Life (QOL) Score as Measured by Symptom Distress Scale (SDS) at End of Study	SDS Scale range: 0 (Worst), 100 (Best), ordinal. Change: score at 16 weeks minus score at baseline. A clinically significant result will be defined as a shift of 10 points on a 0-100 point transformed scale between the average QOL scores of the 3 variants of iron therapy.	Baseline and 16 weeks	No
Secondary	Change From Baseline in Quality of Life (QOL) Score as Measured by Brief Fatigue Inventory(BFI) Fatigue Now Scale at End of Study	Fatigue Now Scale range: 0 (No Fatigue) to 10 (Worst), ordinal. Change: score at 16 weeks minus score at baseline.	Baseline and 16 weeks	No
Secondary	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	FACT-AN Scale range: 0 (Worst) to 100 (Best), ordinal. Change: score at 16 weeks minus score at baseline. A clinically significant result will be defined as a shift of 10 points on a 0-100 point transformed scale between the average QOL scores of the 3 variants of iron therapy.	Baseline and 16 weeks	No
Secondary	C-reactive Protein (CRP) Level at Week 1, Week 7 and Week 16		1 Week, 7 Weeks and 16 Weeks	No
Secondary	Soluble Transferrin Receptor (sTfR)Level at Week 1, Week 7 and Week 16		1 week, 7 weeks and 16 weeks	No
Secondary	Ferritin Level at Baseline, Week 7 and Week 16		Baseline, 7 weeks and 16 weeks	No
Secondary	Mean Corpuscular Volume (MCV) Level at Baseline, Week 7 and Week 16	MCV is a measure of the average red blood cell volume.	Baseline, 7 weeks and 16 weeks	No
Secondary	Transferrin Saturation at Baseline, Week 7 and Week 16		Baseline, 7 weeks and 16 weeks	No