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

Luis Fayad, Stephen Maxted Ansell, Ranjana Advani, Bertrand Coiffier, Robert Stuart, Nancy L. Bartlett, Andres Forero-Torres, Kazimierz Kuliczkowski, David Belada, Edmund Ng, Jonathan G. Drachman

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2569-2578
Number of pages10
JournalLeukemia and Lymphoma
Volume56
Issue number9
DOIs
StatePublished - Sep 2 2015

Fingerprint

Salvage Therapy
Ifosfamide
Lymphoma, Large B-Cell, Diffuse
Carboplatin
Vincristine
Etoposide
Prednisolone
Doxorubicin
Cyclophosphamide
Placebos
Survival
Medical Futility
Rituximab
dacetuzumab
Antigen-Presenting Cells
Cough
Arm
Stem Cells
Demography
Transplants

Keywords

  • Dacetuzumab
  • diffuse large B-cell lymphoma
  • R-ICE
  • salvage therapy
  • stem cell transplant

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

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. / Fayad, Luis; Ansell, Stephen Maxted; Advani, Ranjana; Coiffier, Bertrand; Stuart, Robert; Bartlett, Nancy L.; Forero-Torres, Andres; Kuliczkowski, Kazimierz; Belada, David; Ng, Edmund; Drachman, Jonathan G.

In: Leukemia and Lymphoma, Vol. 56, No. 9, 02.09.2015, p. 2569-2578.

Research output: Contribution to journalArticle

Fayad, Luis ; Ansell, Stephen Maxted ; Advani, Ranjana ; Coiffier, Bertrand ; Stuart, Robert ; Bartlett, Nancy L. ; Forero-Torres, Andres ; Kuliczkowski, Kazimierz ; Belada, David ; Ng, Edmund ; Drachman, Jonathan G. / 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. In: Leukemia and Lymphoma. 2015 ; Vol. 56, No. 9. pp. 2569-2578.
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AU - Coiffier, Bertrand

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AU - Bartlett, Nancy L.

AU - Forero-Torres, Andres

AU - Kuliczkowski, Kazimierz

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