Epoetin Alfa or Darbepoetin Alfa in Treating Patients With Anemia Caused by Chemotherapy

Lymphoma Clinical Trial

Official title:

RC05CB A Pilot, Randomized Comparison of Standard Weekly Epoetin Alfa to Every-3-Week-Epoetin Alfa and Every 3-Week Darbepoetin Alfa

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00416624
• Other study ID #: CDR0000522677
• Secondary ID: P30CA015083RC05C
• Status: Completed
• Phase: Phase 2
• First received: December 27, 2006
• Last updated: October 15, 2014
• Start date: May 2007
• Est. completion date: June 2009

Study information

• Verified date: October 2014
• 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: Epoetin alfa and darbepoetin alfa may cause the body to make more red blood cells. They are used to treat anemia caused by chemotherapy in patients with cancer.

PURPOSE: This randomized clinical trial is studying four different schedules of epoetin alfa or darbepoetin alfa to compare how well they work in treating patients with anemia caused by chemotherapy.

Description:

OBJECTIVES:

Primary

• Compare the relative efficacy of four different erythropoietic agent dosing schedules comprising epoetin alfa or darbepoetin alfa, in terms of the proportion of patients with chemotherapy-associated anemia who achieve a weekly and overall hematopoietic response.

Secondary

• Compare the effect of these regimens on the mean hemoglobin increment measured weekly from baseline to 15 weeks in patients with a baseline hemoglobin of less than or equal to 10.5 g/dL.

• Compare the time required to achieve hemoglobin levels within the goal range 11.0-12.0 g/dL in patients treated with these regimens.

• Compare the effect of these regimens on the proportion of patients requiring red blood cell transfusions and on the number of transfusions required.

• Compare the weekly change in hemoglobin in patients treated with these regimens.

• Compare the need for dose reduction in patients treated with these regimens.

• Compare the adverse event profiles of these regimens in these patients.

• Compare quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, unblinded, pilot study. Patients are stratified according to severity of anemia (mild [hemoglobin ≥ 9.5 g/dL] vs severe [hemoglobin < 9.5 g/dL]), platinum-containing regimen (yes vs no), and tumor type (nonmyeloid hematologic malignancy vs solid tumor). Patients are randomized to 1 of 4 treatment arms.

• Arm I: Patients receive epoetin alfa subcutaneously (SC) on day 1. Treatment repeats weekly for up to 15 courses in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients receive epoetin alfa SC on day 1 (at a higher dose than in arm I). Treatment repeats every 3 weeks for up to 5 courses in the absence of disease progression or unacceptable toxicity.

• Arm III: Patients receive epoetin alfa SC on day 1 (at a higher dose than in arm II). Treatment repeats every 3 weeks for up to 5 courses in the absence of disease progression or unacceptable toxicity.

• Arm IV: Patients receive darbepoetin alfa SC on day 1. Treatment repeats every 3 weeks for up to 5 courses in the absence of disease progression or unacceptable toxicity.

Hemoglobin levels are monitored throughout the study on a weekly basis and before each drug dose is administered. Drug dosing is adjusted (e.g., held, reduced, resumed at a lower dose) as needed to maintain hemoglobin values within the desired ranges.

Quality of life is assessed at baseline and at weeks 4, 7, 10, 13, and 16.

After completion of study treatment, patients are followed at 30 days.

PROJECTED ACCRUAL: A total of 320 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 320
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Diagnosis of solid tumor or nonmyeloid hematologic malignancy (e.g., plasma cell dyscrasia or lymphoproliferative disorder)

• No nonmelanomatous skin cancer

• Hemoglobin = 10.5 g/dL

• Ferritin > 20 ng/mL (i.e., not obviously iron deficient)

• Planning to receive = 12 weeks of anticancer chemotherapy

• Biological therapy (e.g., hypomethylating agents, monoclonal antibodies, or small molecule pathway inhibitors) with an individual or cumulative regimen incidence of grade 3 or 4 anemia > 10% is considered chemotherapy for purposes of this study

• No known anemia secondary to any of the following:

• Cyanocobalamin (vitamin B_12) or folic acid deficiency

• Gastrointestinal bleeding within the past 2 weeks

• Hemolysis

• Myelodysplastic syndromes, myeloproliferative disorders, or acute myeloid leukemia

• No primary hematologic disorder causing chronic moderate to severe anemia (e.g., congenital dyserythropoietic anemia, homozygous hemoglobin S disease or compound heterozygous sickling states, or thalassemia major)

• Carriers of these disease states allowed provided they are not anemic prior to cancer diagnosis

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2

• Life expectancy = 6 months

• Not pregnant or nursing

• No delivery of a baby of = 18 weeks estimated gestational age within the past 3 months (90 days)

• Negative pregnancy test

• Fertile patients must use effective contraception

• Weight > 40.0 kg and < 150.0 kg

• No known hypersensitivity to epoetin alfa, darbepoetin alfa, mammalian-cell derived products, or human albumin

• No uncontrolled hypertension, defined as systolic blood pressure (BP) = 180 mm Hg and/or diastolic BP = 100 mm Hg, despite medical therapy

• No pulmonary emboli and/or deep vein thrombosis within the past 12 months

• Patients actively receiving warfarin for a minimum of 4 weeks are exempted from this requirement

• Prior superficial thrombophlebitis allowed

• No cerebrovascular accident, ischemic stroke, acute coronary syndrome (e.g., unstable angina or Q-wave or non-Q wave myocardial infarction), or other arterial or venous thrombotic events within the past 6 months

• No history of chronic hypercoagulable disorders (e.g., activated protein C resistance, anti-cardiolipin disorder, protein C deficiency, or protein S deficiency)

• Patients receiving anticoagulation therapy (warfarin or acetylsalicyclic acid [aspirin] at a dose of = 325 mg/day) for these conditions are eligible provided therapy is continued during the study period

• History of previously treated seizures allowed provided the patient has been seizure-free for a minimum of 3 months

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• More than 1 year since prior peripheral blood stem cell, bone marrow, or cord blood transplantation

• More than 14 days since prior red blood cell transfusion

• More than 14 days since prior major surgery, including, but not limited to, any of the following:

• Amputation

• Invasion of a body cavity or of the central nervous system using a scalpel, saw, or laser cutting tool

• Resection of a body part (or parts), whether solid or liquid tissue or both, that includes = 1% of a patient's preoperative weight

• The following are not considered major surgery:

• Diagnostic/therapeutic thoracentesis or paracentesis

• Diagnostic skin biopsy

• Digit or fingernail/thumbnail resection or laceration repair under local anesthesia

• Diagnostic fat aspiration

• Otic irrigation to remove cerumen impaction

• Tympanocentesis

• Uncomplicated dental extraction

• Uncomplicated tonsillectomy

• Laser corneal remodeling for refraction purposes

• Cosmetic or therapeutic eyelid surgery

• Bone marrow aspiration and biopsy

• More than 10 weeks since prior darbepoetin alfa, epoetin alfa, or any investigational form of erythropoietin (e.g., gene-activated erythropoietin or novel erythropoiesis stimulating protein)

• No planned stem cell transplantation within the next 4 months (18 weeks)

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, 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

Drug:
• darbepoetin alfa

• epoetin alfa

Procedure:
• fatigue assessment and management

• quality-of-life assessment

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

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 (hemoglobin rise of 2 g/dL from baseline OR achievement of hemoglobin within the goal range)	the proportion of patients who exhibit a hematopoietic response (defined as Hb rise >2 g/dL from baseline or achieving Hb = 11.5 g/dL, whichever occurs first, in the absence of RBC transfusions within 14 days of measurement) during the treatment period	20 weeks
Secondary	Weekly change in hemoglobin levels	To compare the effects of the 3 different epoetin alfa dosing schedules and an every-3-weeks darbepoetin alfa	16 weeks	No
Secondary	Time required to achieve hemoglobin levels within the goal range	To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa	16 weeks	No
Secondary	Proportion of patients requiring red blood cell (RBC) transfusions and the number of transfusions required	To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa	16 weeks	No
Secondary	Dose reduction in each regimen	To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa		No
Secondary	Adverse events as measured by CTCAE v3.0	To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa	16 weeks	No
Secondary	Quality of life as measured by Functional Assessment of Cancer Therapy Scales for Anemia, Linear Analogue Self Assessment measures, Brief Fatigue Inventory, and Symptom Distress Scale at baseline and at 4, 8, 16, and 24 weeks	To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa	16 weeks	No
Secondary	Mean hemoglobin increment week by week	To compare the effects of the 3 different epoetin alfa dosing schedules and an every-3-weeks darbepoetin alfa	16 weeks	No