title: Dacetuzumab plus rituximab, ifosfamide, carboplatin and etoposide as salvage therapy for patients with diffuse large B-cell lymphoma relapsing after rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone: a randomized, double-blind, placebo-controlled phase 2b trial.
abstract: Single-agent dacetuzumab has demonstrated antitumor activity in relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Preclinical data demonstrated improved dacetuzumab antitumor activity in combination with rituximab, ± chemotherapy. We designed a phase 2b, double-blind, placebo-controlled trial to compare rituximab, ifosfamide, carboplatin and etoposide (R-ICE) + dacetuzumab with R-ICE + placebo in patients with DLBCL who relapsed after rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) (ClinicalTrials.gov #NCT00529503). The primary endpoint was complete response (CR); additional endpoints included failure-free survival and overall survival (OS). Overall, 151 patients were randomized (75 dacetuzumab, 76 placebo). No notable differences between arms in demographics or subsequent treatment parameters were observed. Cytopenias, cough and infection were more frequent with dacetuzumab. Futility analysis failed to demonstrate higher CR rates with dacetuzumab (36% dacetuzumab, 42% placebo); consequently, enrollment was stopped. Unplanned post hoc analysis showed that patients who underwent subsequent autologous stem cell transplant experienced improvement in OS (hazard ratio = 0.195, p = 0.004), which may be explained by potential immunomodulatory effects of dacetuzumab on antigen-presenting cells.
authors: a M. D. Anderson Cancer Center , Houston , TX , USA.
authors: Luis
authors: L
authors: Fayad
authors: b Mayo Clinic , Rochester , MN , USA.
authors: Stephen M
authors: SM
authors: Ansell
authors: c Stanford Cancer Center , Stanford , CA , USA.
authors: Ranjana
authors: R
authors: Advani
authors: d Centre Hospitalier Lyon Sud , Pierre Benite , France.
authors: Bertrand
authors: B
authors: Coiffier
authors: e Medical University of South Carolina , Charleston , SC , USA.
authors: Robert
authors: R
authors: Stuart
authors: f Washington University School of Medicine , St. Louis , MO , USA.
authors: Nancy L
authors: NL
authors: Bartlett
authors: g University of Alabama , Birmingham , AL , USA.
authors: Andres
authors: A
authors: Forero-Torres
authors: h Samodzielny Publiczny Szpital Kliniczny , Wroclaw , Poland.
authors: Kazimierz
authors: K
authors: Kuliczkowski
authors: i Charles University in Prague, Faculty of Medicine, University Hospital , Hradec Králové , Czech Republic.
authors: David
authors: D
authors: Belada
authors: j Edmund Ng Consulting LLC , Seattle , WA , USA.
authors: Edmund
authors: E
authors: Ng
authors: k Seattle Genetics, Inc. , Bothell , WA , USA.
authors: Jonathan G
authors: JG
authors: Drachman
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D003371:Cough / Q000139:chemically induced; D003520:Cyclophosphamide / Q000008:administration & dosage; D004311:Double-Blind Method; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011239:Prednisolone / Q000008:administration & dosage; D012074:Remission Induction; D000069283:Rituximab / Q000008:administration & dosage / Q000009:adverse effects; D016879:Salvage Therapy / Q000379:methods*; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000069283:Rituximab; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D011239:Prednisolone; D016190:Carboplatin; D007069:Ifosfamide; C543331:dacetuzumab
keywords: Dacetuzumab; R-ICE; diffuse large B-cell lymphoma; salvage therapy; stem cell transplant