title: Pilot study of dacetuzumab in combination with rituximab and gemcitabine for relapsed or refractory diffuse large B-cell lymphoma.
abstract: Dacetuzumab, a CD40-targeted, humanized antibody, mediates antitumor activity through effector cell functions and direct apoptotic signal transduction. Preclinical studies demonstrated synergistic activity between dacetuzumab, gemcitabine and rituximab against non-Hodgkin lymphoma in vivo. A phase 1b safety/efficacy study of dacetuzumab in combination with rituximab and gemcitabine was conducted in relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Patients received dacetuzumab at doses of 8 or 12 mg/kg IV weekly with rituximab (375 mg/m(2) IV weekly in cycle 1, then every 28 days) and gemcitabine (1000 mg/m(2) IV, days 1, 8 and 15, or days 1 and 15). Thirty-three patients with a median age of 67 years were enrolled. Common adverse events (≥ 15%) were grade 1/2 cytokine release syndrome, nausea, fatigue, thrombocytopenia, headache, decreased appetite, dyspnea, neutropenia, pyrexia, anemia, diarrhea, edema, constipation and cough. Dacetuzumab-related grade 3/4 adverse events occurred infrequently. Six of 30 evaluable patients achieved a complete response (CR) and eight a partial response (PR) per investigator assessment for an overall response rate (ORR) of 47%.
authors: University of Alabama at Birmingham, Birmingham, AL 35294-3300, USA. andres.forero@ccc.uab.edu
authors: Andres
authors: A
authors: Forero-Torres
authors: Nancy
authors: N
authors: Bartlett
authors: Anne
authors: A
authors: Beaven
authors: Han
authors: H
authors: Myint
authors: Sunita
authors: S
authors: Nasta
authors: Donald W
authors: DW
authors: Northfelt
authors: Nancy C
authors: NC
authors: Whiting
authors: Jonathan G
authors: JG
authors: Drachman
authors: Albert F
authors: AF
authors: Lobuglio
authors: Craig H
authors: CH
authors: Moskowitz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012008:Recurrence; D000069283:Rituximab; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D003841:Deoxycytidine; D000069283:Rituximab; C543331:dacetuzumab; D000093542:Gemcitabine