A dose exploration, phase I/II study of administration of continuous erythropoietin receptor activator once every 3 weeks in anemic patients with multiple myeloma receiving chemotherapy.
OBJECTIVE
Continuous erythropoietin receptor activator (C.E.R.A.) is an innovative agent with unique erythropoietin receptor activity and a prolonged half-life, which has the potential for administration at extended dosing intervals. The objectives of this dose-finding study were to evaluate the hemoglobin (Hb) dose-response, pharmacokinetics, and safety of repeated doses of C.E.R.A. given once every 3 weeks to anemic patients with multiple myeloma (MM) receiving chemotherapy.


METHODS
This was an exploratory two-stage, open-label, parallel-group, multicenter study. Patients received C.E.R.A. doses of 1.0, 2.0, 3.5, 4.2, 5.0, 6.5, or 8.0 mg/kg once every 3 weeks by subcutaneous injection initially for 6 weeks, followed by a 12-week optional extension period. The primary outcome measures were the average Hb level and its change from baseline over the initial 6-week period, based on values of the slope of the linear regression analysis and the area under the curve. Rates of Hb response (defined as an increase in Hb of > or =2 g/dL without transfusion) and blood transfusion were also evaluated.


RESULTS
Sixty-four patients entered the study. Dose-related increases in Hb levels were observed during the initial 6-week treatment period for C.E.R.A. doses of 1.0-4.2 mg/kg, with a similar response observed at higher doses. At least 70% of patients receiving 2.0-8.0 mg/kg of C.E.R.A. had Hb responses during the 18-week study. The elimination half-life of C.E.R.A. was found to be long (6.3-9.7 days [151.2-232.8 hours]). All doses were generally well tolerated.


CONCLUSIONS
Based on its unique, long elimination half-life, C.E.R.A. has been demonstrated to be an effective and well-tolerated treatment of anemia given once every 3 weeks to patients with multiple myeloma receiving chemotherapy.
Dmoszynska
Anna
A
Haematooncology and Bone Marrow Transplantation Department, Medical University of Lublin, Lublin, Poland. annadmosz@o2.pl
Kloczko
Janusz
J
Rokicka
Malgorzata
M
Hellmann
Andrzej
A
Spicka
Ivan
I
Eid
Joseph E
JE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000139:chemically induced / Q000517:prevention & control* / Q000628:therapy; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001772:Blood Cell Count; D001794:Blood Pressure; D001803:Blood Transfusion; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004562:Electrocardiography; D004921:Erythropoietin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D006207:Half-Life; D006400:Hematocrit; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D011994:Recombinant Proteins; D012156:Reticulocytes; D016896:Treatment Outcome
D006454:Hemoglobins; D011994:Recombinant Proteins; C508420:continuous erythropoietin receptor activator; D004921:Erythropoietin; D011092:Polyethylene Glycols