User menu

Accès à distance ? S'identifier sur le proxy UCLouvain

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.

Primary tabs

Awan, Farrukh T Hillmen, Peter Hellmann, Andrzej Robak, Tadeusz Hughes, Steven G Bosly, André [UCL] Van Den Neste, Eric [UCL]

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.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2014
Language Anglais
Journal information "British Journal of Haematology" - Vol. 167, no.4, p. 466-477 (2014)
Peer reviewed yes
Publisher Wiley-Blackwell Publishing Ltd. ((United Kingdom) Oxford)
issn 0007-1048
e-issn 1365-2141
Publication status Publié
Affiliations UCL - SSS/DDUV - Institut de Duve
UCL - SSS/IREC - Institut de recherche expérimentale et clinique
UCL - (MGD) Service d'hématologie
UCL - (SLuc) Service d'hématologie
MESH Subject Adult ; Leukemia, Lymphocytic, Chronic, B-Cell ; Male ; Middle Aged ; Recurrence ; Rituximab ; Vidarabine ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal ; Antibodies, Monoclonal, Murine-Derived ; Antineoplastic Combined Chemotherapy Protocols ; Cyclophosphamide ; Female ; Humans
Keywords CD23 ; Chronic lymphocytic leukaemia ; Lumiliximab ; Small lymphocytic lymphoma
Links
  1. Byrd J. C., O'Brien S., Flinn I. W., Kipps T. J., Weiss M., Rai K., Lin T. S., Woodworth J., Wynne D., Reid J., Molina A., Leigh B., Harris S., Phase 1 Study of Lumiliximab with Detailed Pharmacokinetic and Pharmacodynamic Measurements in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia, 10.1158/1078-0432.ccr-06-1463
  2. Byrd J. C., Kipps T. J., Flinn I. W., Castro J., Lin T. S., Wierda W., Heerema N., Woodworth J., Hughes S., Tangri S., Harris S., Wynne D., Molina A., Leigh B., O'Brien S., Phase 1/2 study of lumiliximab combined with fludarabine, cyclophosphamide, and rituximab in patients with relapsed or refractory chronic lymphocytic leukemia, 10.1182/blood-2009-08-237727
  3. Caligaris-Cappio, Journal of Clinical Oncology, 17, 399 (1999)
  4. Cheson, Blood, 87, 4990 (1996)
  5. Christian Beth A., Lin Thomas S., Antibody Therapy for Chronic Lymphocytic Leukemia, 10.1053/j.seminhematol.2008.02.001
  6. Eichhorst, Blood (ASH Annual Meeting Abstracts), 122, 526 (2013)
  7. Fischer Kirsten, Cramer Paula, Busch Raymonde, Böttcher Sebastian, Bahlo Jasmin, Schubert Jöerg, Pflüger Karl H., Schott Silke, Goede Valentin, Isfort Susanne, von Tresckow Julia, Fink Anna-Maria, Bühler Andreas, Winkler Dirk, Kreuzer Karl-Anton, Staib Peter, Ritgen Matthias, Kneba Michael, Döhner Hartmut, Eichhorst Barbara F., Hallek Michael, Stilgenbauer Stephan, Wendtner Clemens-Martin, Bendamustine in Combination With Rituximab for Previously Untreated Patients With Chronic Lymphocytic Leukemia: A Multicenter Phase II Trial of the German Chronic Lymphocytic Leukemia Study Group, 10.1200/jco.2011.39.2688
  8. Fournier S, Delespesse G, Rubio M, Biron G, Sarfati M, CD23 antigen regulation and signaling in chronic lymphocytic leukemia., 10.1172/jci115717
  9. Gordon, Monographs in Allergy, 29, 156 (1991)
  10. Hallek M, Fischer K, Fingerle-Rowson G, Fink AM, Busch R, Mayer J, Hensel M, Hopfinger G, Hess G, von Grünhagen U, Bergmann M, Catalano J, Zinzani PL, Caligaris-Cappio F, Seymour JF, Berrebi A, Jäger U, Cazin B, Trneny M, Westermann A, Wendtner CM, Eichhorst BF, Staib P, Bühler A, Winkler D, Zenz T, Böttcher S, Ritgen M, Mendila M, Kneba M, Döhner H, Stilgenbauer S, Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial, 10.1016/s0140-6736(10)61381-5
  11. International Conference on Harmonization 2009 Introductory Guide for Standardised Medical Dictionary for Regulatory Activities (MedDRA@) terminology Queries (SMQs) Version 12.0 http://www.meddra.org/sites/default/files/guidance/file/smq_intguide_12_0_english.pdf
  12. Keating Michael J., O’Brien Susan, Albitar Maher, Lerner Susan, Plunkett William, Giles Francis, Andreeff Michael, Cortes Jorge, Faderl Stefan, Thomas Deborah, Koller Charles, Wierda William, Detry Michelle A., Lynn Alice, Kantarjian Hagop, Early Results of a Chemoimmunotherapy Regimen of Fludarabine, Cyclophosphamide, and Rituximab As Initial Therapy for Chronic Lymphocytic Leukemia, 10.1200/jco.2005.12.051
  13. Kijimoto-Ochiai S., CD23 (the low-affinity IgE receptor) as a C-type lectin: a multidomain and multifunctional molecule, 10.1007/s00018-002-8455-1
  14. Kijimoto-Ochiai Shigeko, Noguchi Atsutaka, Ohnishi Toshiyuki, Araki Yoshio, Complex Formation of CD23/Surface Immunoglobulin and CD23/CD81/MHC Class II on an EBV-Transformed Human B Cell Line and Inferable Role of Tetraspanin, 10.1111/j.1348-0421.2004.tb03531.x
  15. Lampert Irvin A, Wotherspoon Andrew, Van Noorden Susan, Hasserjian Robert P, High expression of CD23 in the proliferation centers of chronic lymphocytic leukemia in lymph nodes and spleen, 10.1016/s0046-8177(99)90089-8
  16. Liu Yong-Jun, Cairns Jennifer A., Holder Michelle J., Abbot Sandra D., Jansen Katherin U., Bonnefoy Jean-Yves, Gordon John, Maclennan Ian C. M., Recombinant 25-kDa CD23 and interleukin 1α promote the survival of germinal center B cells: evidence for bifurcation in the development of centrocytes rescued from apoptosis, 10.1002/eji.1830210504
  17. Lopez-Matas, Haematologica, 85, 1140 (2000)
  18. Oken Martin M., Creech Richard H., Tormey Douglass C., Horton John, Davis Thomas E., McFadden Eleanor T., Carbone Paul P., Toxicity and response criteria of the Eastern Cooperative Oncology Group : , 10.1097/00000421-198212000-00014
  19. Pathan N. I., Chu P., Hariharan K., Cheney C., Molina A., Byrd J., Mediation of apoptosis by and antitumor activity of lumiliximab in chronic lymphocytic leukemia cells and CD23+ lymphoma cell lines, 10.1182/blood-2007-03-082024
  20. Reichert, Current Opinion in Molecular Therapeutics, 6, 675 (2004)
  21. Robak Tadeusz, Novel Monoclonal Antibodies for the Treatment of Chronic Lymphocytic Leukemia, 10.2174/156800908783769319
  22. Robak Tadeusz, Dmoszynska Anna, Solal-Céligny Philippe, Warzocha Krzysztof, Loscertales Javier, Catalano John, Afanasiev Boris V., Larratt Loree, Geisler Christian H., Montillo Marco, Zyuzgin Ilya, Ganly Peter S., Dartigeas Caroline, Rosta András, Maurer Jörg, Mendila Myriam, Saville M. Wayne, Valente Nancy, Wenger Michael K., Moiseev Sergey I., Rituximab Plus Fludarabine and Cyclophosphamide Prolongs Progression-Free Survival Compared With Fludarabine and Cyclophosphamide Alone in Previously Treated Chronic Lymphocytic Leukemia, 10.1200/jco.2009.26.4556
  23. Sarfati, Blood, 88, 4259 (1996)
  24. Strati Paolo, Wierda William, Burger Jan, Ferrajoli Alessandra, Tam Constantine, Lerner Susan, Keating Michael J., O'Brien Susan, Myelosuppression after frontline fludarabine, cyclophosphamide, and rituximab in patients with chronic lymphocytic leukemia : Analysis of persistent and new-onset cytopenia, 10.1002/cncr.28318
  25. Tam Constantine S., Wolf Max, Prince H. Miles, Januszewicz E. Henry, Westerman David, Lin Katherine I., Carney Dennis, Seymour John F., Fludarabine, cyclophosphamide, and rituximab for the treatment of patients with chronic lymphocytic leukemia or indolent non-hodgkin lymphoma : FC and Rituximab for CLL and Indolent NHL, 10.1002/cncr.21882
  26. Tam C. S., O'Brien S., Wierda W., Kantarjian H., Wen S., Do K.-A., Thomas D. A., Cortes J., Lerner S., Keating M. J., Long-term results of the fludarabine, cyclophosphamide, and rituximab regimen as initial therapy of chronic lymphocytic leukemia, 10.1182/blood-2008-02-140582
  27. Wierda William, O’Brien Susan, Wen Sijin, Faderl Stefan, Garcia-Manero Guillermo, Thomas Deborah, Do Kim-Anh, Cortes Jorge, Koller Charles, Beran Miloslav, Ferrajoli Alessandra, Giles Francis, Lerner Susan, Albitar Maher, Kantarjian Hagop, Keating Michael, Chemoimmunotherapy With Fludarabine, Cyclophosphamide, and Rituximab for Relapsed and Refractory Chronic Lymphocytic Leukemia, 10.1200/jco.2005.12.516
  28. Wierda William, O'Brien Susan, Faderl Stefan, Ferrajoli Alessandra, Wang Xuemei, Do Kim-Anh, Garcia-Manero Guillermo, Thomas Deborah, Cortes Jorge, Ravandi-Kashani Farhad, Giles Francis, Lerner Susan, Kantarjian Hagop, Keating Michael, A retrospective comparison of three sequential groups of patients with Recurrent/Refractory chronic lymphocytic leukemia treated with fludarabine-based regimens, 10.1002/cncr.21554
  29. Zhou, Modern Pathology, 25, 237 (2012)
Bibliographic reference Awan, Farrukh T ; Hillmen, Peter ; Hellmann, Andrzej ; Robak, Tadeusz ; Hughes, Steven G ; et. al. 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, Vol. 167, no.4, p. 466-477 (2014)
Permanent URL http://hdl.handle.net/2078.1/175770