942TiP - Phase 3 trial of pixantrone plus rituximab versus gemcitabine plus rituximab in treating relapsed/refractory transplant-ineligible aggressive non-H...

Date 08 October 2016
Event ESMO 2016 Congress
Session Poster Display
Topics Cytotoxic agents
Lymphomas
Therapy
Biological therapy
Presenter Pencho Georgiev
Citation Annals of Oncology (2016) 27 (6): 313-327. 10.1093/annonc/mdw375
Authors P.G. Georgiev1, D. Belada2, S. Dakhil3, L.F. Inhorn4, D. Andorsky5, A.M. Liberati6, J.T. Beck7, D. Quick8, C. Patti9, L. Sivcheva10, J.M. Zaucha11, R. Pettengell12, T. Devries13, J.P. Dean14, M. Pavlyuk15, N. Failloux15, K. Hübel16
  • 1Clinic Of Hematology, UMBAL Sv.Georgi, 4002 - Plovdiv/BG
  • 24th Department Of Internal Medicine - Hematology, Faculty of Medicine of Charles University in Pragu, Hradec Kralove/CZ
  • 3Hematology, Cancer Center of Kansas, Wichita/US
  • 4Hematology, Blue Ridge Cancer Care, Roanoke/US
  • 5Hematology, Rocky Mountain Cancer Center, Boulder/US
  • 6Hematology, Azienda Ospedaliera Sta Maria, Terni/IT
  • 7Hematology, Highlands Oncology Group, Lafayetteville/US
  • 8Hematology, Joe Arrington Cancer Research and Treatment Center, Lubbock/US
  • 9Hematology, Ospedali Riuniti Villa Sofia-Cervello, Palermo/IT
  • 10Hematology, MHAT Hristo Botev, Vratsa/BG
  • 11Hematology, Medical University of Gdansk, Gdansk/PL
  • 12Hematology, St George's Healthcare NHS Trust, London/GB
  • 13Biostatistics, CTI Bioparma Corp, Seattle/US
  • 14R&d, CTI Bioparma Corp, Seattle/US
  • 15R&d, Institut de Recherches Internationales Servier, Suresnes/FR
  • 16Hematology, University Hopsital of Cologne, Koln/DE

Abstract

Background

Aggressive non-Hodgkin's lymphoma (NHL) comprises 44% of all NHL, and diffuse large B-cell lymphoma (DLBCL) is the most common subtype. Anthracycline-based regimens are the standard of care for front-line therapy. There is currently no standard treatment for relapsed/refractory (R/R) aggressive NHL beyond second-line for patients who are not transplant-eligible. Pixantrone is a novel aza-anthracenedione designed to have less cardiac toxicity than the anthracyclines. A phase 3 study of monotherapy with pixantrone versus comparator gave results that were sufficiently promising for conditional European approval for the treatment of multiply R/R aggressive B-cell NHL. We set up a phase 3 trial to explore the efficacy of combining pixantrone with rituximab, which responds to one of the European post-authorization measures.

Trial design

We are enrolling adult patients with DLBCL or follicular grade 3 lymphoma who have relapsed after at least one multiagent chemotherapy containing rituximab. All participants are ineligible for stem cell transplantation, with Eastern Cooperative Oncology Group score ≤2 and normal cardiac function. Centers have been opened in the USA and Europe (Austria, Belgium, Bulgaria, Czech Republic, Denmark, France, Germany, Hungary, Italy, Poland, Romania, Russia, Slovakia, Spain, UK, and Ukraine). Included patients will be randomly allocated to receive up to six 28-day cycles of pixantrone (50 mg/m2 IV on days 1, 8, 15) plus rituximab (375 mg/m2 IV on day 1) or gemcitabine (1000 mg/m2 IV on days 1, 8, 15) plus rituximab (375 mg/m2 IV on day 1). To complete 6 cycles, patients who discontinue one study drug due to toxicity may continue with the other assigned study drug. The primary endpoint is progression-free survival; secondary endpoints include overall survival, overall response rate, and safety. Recruitment is ongoing.

Clinical trial identification

NCT01321541

Legal entity responsible for the study

CTI Biopharma Corp

Funding

CTI Biopharma Corp

Disclosure

P.G. Georgiev, D. Belada, S. Dakhil, L.F. Inhorn, D. Andorsky, A.M. Liberati, J.T. Beck, D. Quick, C. Patti, L. Sivcheva, J.M. Zaucha, R. Pettengell, K. Hübel: Honoraria, research grants, or both from Servier or CTI Biopharma Corp. T. Devries, J.P. Dean: Employee of CTI Biopharma Corp. M. Pavlyuk, N. Failloux: Employee of Servier