Phase II study of melphalan, thalidomide and prednisone combined with oral panobinostat in patients with relapsed/refractory multiple myeloma

Leukemia and Lymphoma

Volumn 53, Issue 9, 2012, Pages 1722-1727

  Offidani, Massimo ^a   Polloni, Claudia ^a   Cavallo, Federica ^b   Marina Liberati, Anna ^c   Ballanti, Stelvio ^d   Pulini, Stefano ^e   Catarini, Massimo ^f   Alesiani, Francesco ^g   Corvatta, Laura ^h   Gentili, Silvia ^a   Caraffa, Patrizia ^a   Boccadoro, Mario ^b   Leoni, Pietro ^a   Palumbo, Antonio ^b  

^a OSPEDALI RIUNITI   (Italy)

^b Azienda Ospedaliero Universitaria S Giovanni Battista   (Italy)

^c Azienda Ospealiera S Maria   (Italy)

^d UNIVERSITY OF PERUGIA   (Italy)

^e SPIRITO SANTO HOSPITAL   (Italy)

^f Ospedale Generale Provinciale   (Italy)

^g Unità Oncoematologia   (Italy)

^h Divisione di Medicina   (Italy)

Author keywords

Multiple myeloma; panobinostat; relapsed refractory

Indexed keywords

BORTEZOMIB; GRANULOCYTE COLONY STIMULATING FACTOR; LENALIDOMIDE; MELPHALAN; PANOBINOSTAT; PREDNISONE; THALIDOMIDE;

ADULT; AGED; ANEMIA; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER PATIENT; CLINICAL ARTICLE; CONTINUOUS INFUSION; CONTROLLED STUDY; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG FATALITY; DRUG RESPONSE; DRUG SAFETY; DRUG TOLERANCE; ERYTHROCYTE TRANSFUSION; FATIGUE; FEBRILE NEUTROPENIA; FEMALE; HEART ATRIUM FIBRILLATION; HUMAN; MALE; MAXIMUM TOLERATED DOSE; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; MULTIPLE MYELOMA; NEUTROPENIA; PATIENT COMPLIANCE; PERIPHERAL NEUROPATHY; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; RECURRENT DISEASE; THROMBOCYTE TRANSFUSION; THROMBOCYTOPENIA; THROMBOEMBOLISM;

AGED; AGED, 80 AND OVER; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; DISEASE-FREE SURVIVAL; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG ADMINISTRATION SCHEDULE; DRUG RESISTANCE, NEOPLASM; FEMALE; HUMANS; HYDROXAMIC ACIDS; INDOLES; MALE; MELPHALAN; MIDDLE AGED; MULTIPLE MYELOMA; NEOPLASM STAGING; NEUTROPENIA; PREDNISONE; RECURRENCE; THALIDOMIDE; THROMBOCYTOPENIA; TIME FACTORS; TREATMENT OUTCOME;

EID: 84862895569     PISSN: 10428194     EISSN: 10292403     Source Type: Journal    
DOI: 10.3109/10428194.2012.664844     Document Type: Article

References (25)

1. Kapoor P, Rajkumar SV, Dispenzieri A, et al. Melphalan and prednisone versus melphalan, prednisone and thalidomide for elderly and/or transplant ineligible patients with multiple myeloma: A metaanalysis. Leukemia 2011;25:689-696.
2. S an Miguel JF, Schlag R, Khuageva NK, et a l. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med 2008;359:906-917.
3. R ajkumar SV, Jacobus S, Callander NS, et al. Lenalidomide plus highdose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: An open label randomised controlled trial. Lancet Oncol 2010;11:29-37.
4. P alumbo A, Avonto I, Bruno B, et al. Intravenous melphalan, thalidomide and prednisone in refractory and relapsed multiple myeloma. Eur J Haematol 2006;76:273-277.
5. L ane A, Chabner BA. Histone deacetylase inhibitors in cancer therapy. J Clin Oncol 2009;27:5459-5468.
6. C ameron EE, Bachman KE, Myohanen S, Myöhänen S, Herman JG, Baylin SB. Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nat Genet 1999;2:103-107.
7. M edina V, Edmonds B, Young GP, et a l. Induction of caspase-3 protease activity and apoptosis by butyrate and trichostatin(inhibitors of histone deacetylase): dependence on protein synthesis and synergy with a mitochondrial/cytochrome c-dependent pathway. Cancer Res 1997;57:3697-3707.
8. C atley L, Weisberg E, Kiziltepe T, et a l. Aggresome induction by proteasome inhibitor bortezomib and alpha-tubulin hyperacetylation by tubulin deacetylase (TDAC) inhibitor LBH589 are synergistic in myeloma cells. Blood 2006;108:3441-3449.
9. M aiso P, Carvajal-Vergara X, Ocio EM, et al. Th e histone deacetylase inhibitor LBH589 is a potent antimyeloma agent that overcomes drug resistance. Cancer Res 2006;15:5250-5257.
10. O cio EM, Vilanova D, Atadja P, et a l. In vitro and in vivo rationale for the triple combination of panobinostat (LBH589) and dexamethasone with either bortezomib or lenalidomide in multiple myeloma. Haematologica 2010;95:794-803.
11. S anchez E, Shen J, Steinberg J, et al. Th e histone deacetylase inhibitor LBH589 enhances the anti-myeloma eff ects of chemotherapy in vitro and in vivo. Leuk Res 2011;35:373-379.
12. P rince HM, George D, Patnaik A, et a l. Phase I study of oral LBH589, a novel deacetylase (DAC) inhibitor in advanced solid tumors and non-Hodgkin's lymphoma. J Clin Oncol 2007;25(18 Suppl.): Abstract 3500.
13. D uvic M, Becker JC, Dalle S, et a l. Phase II trial of oral panobinostat (LBH589) in patients with refractory cutaneous T-cell lymphoma (CTCL). Blood 2008;112(Suppl. 1): Abstract 1005.
14. Sureda A,Younes A, Ben-Yehuda D, et al. Final analysis: phase II study of oral panobinostat in relapsed/refractory Hodgkin lymphoma patients following autologous hematopoietic stem cell transplant. Blood 2010;116(Suppl. 1): Abstract 419.
15. O ttmann OG, Spencer A, Prince HM, et al. Phase IA/II study of oral panobinostat (LBH589), a novel pan-deacetylase inhibitor (DACi) demonstrating effi cacy in patients with advanced hematologic malignancies. Blood 2008;112(Suppl. 1): Abstract 1005.
16. W olf JL, Siegel D, Matous J, et a l. A phase II study of oral panobinostat (LBH589) in adult patients with advanced refractory multiple myeloma. Blood 2008;112(Suppl. 1): Abstract 2774.
17. Bryant J, Day R. Incorporating toxicity considerations into the design of two-stage phase II clinical trials. Biometrics 1995;51: 1372-1383.
18. Durie B, Harousseau J-L, San Miguel JS, et al. International uniform response criteria for multiple myeloma. Leukemia 2006;20:1467-1473.
19. M ateos M, Spencer A, Taylor K, et a l. Phase Ib study of oral panobinostat (LBH589) plus lenaldomide (LEN) plus dexamethasone (DEX) in patients with relapsed (Rel) and refractory (Ref) multiple myeloma (MM). J Clin Oncol 2010;28(15 Suppl.): Abstract 8030.
20. San Miguel JF, Sezer O, Siegel DS, et al. Phase Ib study of oral panobinostat (LBH589) plus intravenous bortezomib in patients with relapsed (Rel) or refractory (Ref) multiple myeloma (MM). J Clin Oncol 2010;28(15 Suppl.): Abstract 8001.
21. Berenson J, Yellin O, Kazamel T, et a l. A phase I/II study of oral elphalan (Mel) combined with panobinostat (Pan) for patients with relapsed or refractory multiple myeloma. Haematologica 2011;96(Suppl. 1):P-206.
22. Giver CR, Jaye DL, Waller EK, et a l. Rapid recovery from panobinostat (LBH589)-induced thrombocytopenia in mice involves a rebound eff ect of bone marrow megakaryocytes. Leukemia 2011;25:362-365.
23. Bishton MJ, Harrison SJ, Martin BP, et al. Deciphering the molecular and biologic processes that mediate histone deacetylase inhibitor-induced thrombocytopenia. Blood 2011;117:3658-3668.
24. S chlossman R, Alsina M, Weber D, et a l. Panorama 2: A phase II study of panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory multiple myeloma. Haematologica 2011;96(Suppl. 2): Abstract 0900.
25. J ones PA, Baylin SB. Th e epigenomics of cancer. Cell 2007;128: 683-692.