A randomized, open-label, multicentre, phase 2/3 study to evaluate the safety and efficacy of lumiliximab in combination with fludarabine, cyclophosphamide and rituximab versus fludarabine, cyclophosphamide and rituximab alone in subjects with relapsed chronic lymphocytic leukaemia

Farrukh T. Awan, Peter Hillmen, Andrzej Hellmann, Tadeusz Robak, Steven G. Hughes, Denise Trone, Megan Shannon, Ian W. Flinn, John C. Byrd, Dardo Riveros, Santiago Pavlovsky, Claudio M. Iastrebner, Dennis A. Carney, Sandra Deveridge, Simon Durrant, Uwe H. Hahn, Mark Hertzberg, Michael F. Leahy, David Ma, Paula MarltonStephen Mulligan, Stephen S. Opat, Campbell Tiley, Nicholas W. Wickham, Paul Cannell, John Gatalano, John Catalano, Gavin Cull, Luen B. To, Georg Hopfinger, Ulrich Jager, Werner Linkesch, Andreas Petzer, Josef Schwarzmeier, Michael Steurer, Richard Greil, Zwi Bememan, Andre Bosly, Dominique Bron, Ann Janssens, Fritz Offner, Eric W. Van Den Neste, Ka Lung Wu, Achiel Van Hoof, Angelo Maiolino, Helio Pinczowski, Maria A. Zanichelli, Angelo M. Carella, Federico Caligaris-Cappio, Armando Santoro, on behalf of the LUCID trial investigators

Research output: Contribution to journalArticle

Abstract

Summary: Lumiliximab is a chimeric monoclonal antibody that targets CD23 on the surface of chronic lymphocytic leukaemia (CLL) B-cells. Early phase clinical studies with lumiliximab alone and in combination with fludarabine, cyclophosphamide and rituximab (FCR) established its potential efficacy and tolerability. The 152CL201 trial [Lumiliximab with fludarabine, cyclophosphamide and rituximab (FCR) versus FCR alone in subjects with relapsed CLL; LUCID] was a phase 2/3, randomized (1:1), open-label, multicentre study of lumiliximab in combination with FCR versus FCR alone in patients with relapsed CLL. Six hundred and twenty-seven patients were randomized to either arm. Overall the combination of lumiliximab with FCR was not significantly better than FCR alone (overall response rate 71% vs. 72%, complete response rate 16% vs. 15%, median progression-free survival 24.6 vs. 23.9 months respectively, for FCR with and without lumiliximab). There was a slightly increased incidence of adverse events with lumiliximab but these increases did not appear to lead to differences in eventual outcomes. An interim analysis failed to show sufficient efficacy of the combination of lumiliximab with FCR. The study was therefore stopped early for lack of efficacy. Despite the eventual outcome, the LUCID trial is one of the largest studies that provides valuable insight into the efficacy and tolerability of FCR as a therapeutic option for patients with relapsed CLL.

Original languageEnglish
Pages (from-to)466-477
Number of pages12
JournalBritish Journal of Haematology
Volume167
Issue number4
DOIs
Publication statusPublished - Nov 1 2014

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B-Cell Chronic Lymphocytic Leukemia
Cyclophosphamide
Safety
lumiliximab
fludarabine
Rituximab
Multicenter Studies
Disease-Free Survival
Monoclonal Antibodies
Incidence

Keywords

  • CD23
  • Chronic lymphocytic leukaemia
  • Lumiliximab
  • Small lymphocytic lymphoma

ASJC Scopus subject areas

  • Hematology
  • Medicine(all)

Cite this

A randomized, open-label, multicentre, phase 2/3 study to evaluate the safety and efficacy of lumiliximab in combination with fludarabine, cyclophosphamide and rituximab versus fludarabine, cyclophosphamide and rituximab alone in subjects with relapsed chronic lymphocytic leukaemia. / Awan, Farrukh T.; Hillmen, Peter; Hellmann, Andrzej; Robak, Tadeusz; Hughes, Steven G.; Trone, Denise; Shannon, Megan; Flinn, Ian W.; Byrd, John C.; Riveros, Dardo; Pavlovsky, Santiago; Iastrebner, Claudio M.; Carney, Dennis A.; Deveridge, Sandra; Durrant, Simon; Hahn, Uwe H.; Hertzberg, Mark; Leahy, Michael F.; Ma, David; Marlton, Paula; Mulligan, Stephen; Opat, Stephen S.; Tiley, Campbell; Wickham, Nicholas W.; Cannell, Paul; Gatalano, John; Catalano, John; Cull, Gavin; To, Luen B.; Hopfinger, Georg; Jager, Ulrich; Linkesch, Werner; Petzer, Andreas; Schwarzmeier, Josef; Steurer, Michael; Greil, Richard; Bememan, Zwi; Bosly, Andre; Bron, Dominique; Janssens, Ann; Offner, Fritz; Van Den Neste, Eric W.; Wu, Ka Lung; Van Hoof, Achiel; Maiolino, Angelo; Pinczowski, Helio; Zanichelli, Maria A.; Carella, Angelo M.; Caligaris-Cappio, Federico; Santoro, Armando; on behalf of the LUCID trial investigators.

In: British Journal of Haematology, Vol. 167, No. 4, 01.11.2014, p. 466-477.

Research output: Contribution to journalArticle

Awan, FT, Hillmen, P, Hellmann, A, Robak, T, Hughes, SG, Trone, D, Shannon, M, Flinn, IW, Byrd, JC, Riveros, D, Pavlovsky, S, Iastrebner, CM, Carney, DA, Deveridge, S, Durrant, S, Hahn, UH, Hertzberg, M, Leahy, MF, Ma, D, Marlton, P, Mulligan, S, Opat, SS, Tiley, C, Wickham, NW, Cannell, P, Gatalano, J, Catalano, J, Cull, G, To, LB, Hopfinger, G, Jager, U, Linkesch, W, Petzer, A, Schwarzmeier, J, Steurer, M, Greil, R, Bememan, Z, Bosly, A, Bron, D, Janssens, A, Offner, F, Van Den Neste, EW, Wu, KL, Van Hoof, A, Maiolino, A, Pinczowski, H, Zanichelli, MA, Carella, AM, Caligaris-Cappio, F, Santoro, A & on behalf of the LUCID trial investigators 2014, 'A randomized, open-label, multicentre, phase 2/3 study to evaluate the safety and efficacy of lumiliximab in combination with fludarabine, cyclophosphamide and rituximab versus fludarabine, cyclophosphamide and rituximab alone in subjects with relapsed chronic lymphocytic leukaemia', British Journal of Haematology, vol. 167, no. 4, pp. 466-477. https://doi.org/10.1111/bjh.13061
Awan, Farrukh T. ; Hillmen, Peter ; Hellmann, Andrzej ; Robak, Tadeusz ; Hughes, Steven G. ; Trone, Denise ; Shannon, Megan ; Flinn, Ian W. ; Byrd, John C. ; Riveros, Dardo ; Pavlovsky, Santiago ; Iastrebner, Claudio M. ; Carney, Dennis A. ; Deveridge, Sandra ; Durrant, Simon ; Hahn, Uwe H. ; Hertzberg, Mark ; Leahy, Michael F. ; Ma, David ; Marlton, Paula ; Mulligan, Stephen ; Opat, Stephen S. ; Tiley, Campbell ; Wickham, Nicholas W. ; Cannell, Paul ; Gatalano, John ; Catalano, John ; Cull, Gavin ; To, Luen B. ; Hopfinger, Georg ; Jager, Ulrich ; Linkesch, Werner ; Petzer, Andreas ; Schwarzmeier, Josef ; Steurer, Michael ; Greil, Richard ; Bememan, Zwi ; Bosly, Andre ; Bron, Dominique ; Janssens, Ann ; Offner, Fritz ; Van Den Neste, Eric W. ; Wu, Ka Lung ; Van Hoof, Achiel ; Maiolino, Angelo ; Pinczowski, Helio ; Zanichelli, Maria A. ; Carella, Angelo M. ; Caligaris-Cappio, Federico ; Santoro, Armando ; on behalf of the LUCID trial investigators. / A randomized, open-label, multicentre, phase 2/3 study to evaluate the safety and efficacy of lumiliximab in combination with fludarabine, cyclophosphamide and rituximab versus fludarabine, cyclophosphamide and rituximab alone in subjects with relapsed chronic lymphocytic leukaemia. In: British Journal of Haematology. 2014 ; Vol. 167, No. 4. pp. 466-477.
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abstract = "Summary: Lumiliximab is a chimeric monoclonal antibody that targets CD23 on the surface of chronic lymphocytic leukaemia (CLL) B-cells. Early phase clinical studies with lumiliximab alone and in combination with fludarabine, cyclophosphamide and rituximab (FCR) established its potential efficacy and tolerability. The 152CL201 trial [Lumiliximab with fludarabine, cyclophosphamide and rituximab (FCR) versus FCR alone in subjects with relapsed CLL; LUCID] was a phase 2/3, randomized (1:1), open-label, multicentre study of lumiliximab in combination with FCR versus FCR alone in patients with relapsed CLL. Six hundred and twenty-seven patients were randomized to either arm. Overall the combination of lumiliximab with FCR was not significantly better than FCR alone (overall response rate 71{\%} vs. 72{\%}, complete response rate 16{\%} vs. 15{\%}, median progression-free survival 24.6 vs. 23.9 months respectively, for FCR with and without lumiliximab). There was a slightly increased incidence of adverse events with lumiliximab but these increases did not appear to lead to differences in eventual outcomes. An interim analysis failed to show sufficient efficacy of the combination of lumiliximab with FCR. The study was therefore stopped early for lack of efficacy. Despite the eventual outcome, the LUCID trial is one of the largest studies that provides valuable insight into the efficacy and tolerability of FCR as a therapeutic option for patients with relapsed CLL.",
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T1 - A randomized, open-label, multicentre, phase 2/3 study to evaluate the safety and efficacy of lumiliximab in combination with fludarabine, cyclophosphamide and rituximab versus fludarabine, cyclophosphamide and rituximab alone in subjects with relapsed chronic lymphocytic leukaemia

AU - Awan, Farrukh T.

AU - Hillmen, Peter

AU - Hellmann, Andrzej

AU - Robak, Tadeusz

AU - Hughes, Steven G.

AU - Trone, Denise

AU - Shannon, Megan

AU - Flinn, Ian W.

AU - Byrd, John C.

AU - Riveros, Dardo

AU - Pavlovsky, Santiago

AU - Iastrebner, Claudio M.

AU - Carney, Dennis A.

AU - Deveridge, Sandra

AU - Durrant, Simon

AU - Hahn, Uwe H.

AU - Hertzberg, Mark

AU - Leahy, Michael F.

AU - Ma, David

AU - Marlton, Paula

AU - Mulligan, Stephen

AU - Opat, Stephen S.

AU - Tiley, Campbell

AU - Wickham, Nicholas W.

AU - Cannell, Paul

AU - Gatalano, John

AU - Catalano, John

AU - Cull, Gavin

AU - To, Luen B.

AU - Hopfinger, Georg

AU - Jager, Ulrich

AU - Linkesch, Werner

AU - Petzer, Andreas

AU - Schwarzmeier, Josef

AU - Steurer, Michael

AU - Greil, Richard

AU - Bememan, Zwi

AU - Bosly, Andre

AU - Bron, Dominique

AU - Janssens, Ann

AU - Offner, Fritz

AU - Van Den Neste, Eric W.

AU - Wu, Ka Lung

AU - Van Hoof, Achiel

AU - Maiolino, Angelo

AU - Pinczowski, Helio

AU - Zanichelli, Maria A.

AU - Carella, Angelo M.

AU - Caligaris-Cappio, Federico

AU - Santoro, Armando

AU - on behalf of the LUCID trial investigators

PY - 2014/11/1

Y1 - 2014/11/1

N2 - Summary: Lumiliximab is a chimeric monoclonal antibody that targets CD23 on the surface of chronic lymphocytic leukaemia (CLL) B-cells. Early phase clinical studies with lumiliximab alone and in combination with fludarabine, cyclophosphamide and rituximab (FCR) established its potential efficacy and tolerability. The 152CL201 trial [Lumiliximab with fludarabine, cyclophosphamide and rituximab (FCR) versus FCR alone in subjects with relapsed CLL; LUCID] was a phase 2/3, randomized (1:1), open-label, multicentre study of lumiliximab in combination with FCR versus FCR alone in patients with relapsed CLL. Six hundred and twenty-seven patients were randomized to either arm. Overall the combination of lumiliximab with FCR was not significantly better than FCR alone (overall response rate 71% vs. 72%, complete response rate 16% vs. 15%, median progression-free survival 24.6 vs. 23.9 months respectively, for FCR with and without lumiliximab). There was a slightly increased incidence of adverse events with lumiliximab but these increases did not appear to lead to differences in eventual outcomes. An interim analysis failed to show sufficient efficacy of the combination of lumiliximab with FCR. The study was therefore stopped early for lack of efficacy. Despite the eventual outcome, the LUCID trial is one of the largest studies that provides valuable insight into the efficacy and tolerability of FCR as a therapeutic option for patients with relapsed CLL.

AB - Summary: Lumiliximab is a chimeric monoclonal antibody that targets CD23 on the surface of chronic lymphocytic leukaemia (CLL) B-cells. Early phase clinical studies with lumiliximab alone and in combination with fludarabine, cyclophosphamide and rituximab (FCR) established its potential efficacy and tolerability. The 152CL201 trial [Lumiliximab with fludarabine, cyclophosphamide and rituximab (FCR) versus FCR alone in subjects with relapsed CLL; LUCID] was a phase 2/3, randomized (1:1), open-label, multicentre study of lumiliximab in combination with FCR versus FCR alone in patients with relapsed CLL. Six hundred and twenty-seven patients were randomized to either arm. Overall the combination of lumiliximab with FCR was not significantly better than FCR alone (overall response rate 71% vs. 72%, complete response rate 16% vs. 15%, median progression-free survival 24.6 vs. 23.9 months respectively, for FCR with and without lumiliximab). There was a slightly increased incidence of adverse events with lumiliximab but these increases did not appear to lead to differences in eventual outcomes. An interim analysis failed to show sufficient efficacy of the combination of lumiliximab with FCR. The study was therefore stopped early for lack of efficacy. Despite the eventual outcome, the LUCID trial is one of the largest studies that provides valuable insight into the efficacy and tolerability of FCR as a therapeutic option for patients with relapsed CLL.

KW - CD23

KW - Chronic lymphocytic leukaemia

KW - Lumiliximab

KW - Small lymphocytic lymphoma

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