title: Phase 1/2 study of carfilzomib plus melphalan and prednisone in patients aged over 65 years with newly diagnosed multiple myeloma.
abstract: This phase 1/2 dose-escalation study investigated the combination of carfilzomib with melphalan and prednisone (CMP) in patients aged >65 years with newly diagnosed multiple myeloma (MM). Melphalan and prednisone were administered orally on days 1 to 4; carfilzomib was IV administered on days 1, 2, 8, 9, 22, 23, 29, and 30 of a 42-day cycle. Patients received up to 9 cycles of CMP. In the phase 1 dose-escalation portion, the primary objectives were to determine the incidence of dose-limiting toxicities during the first cycle of CMP treatment to define the maximal tolerated dose (MTD) of carfilzomib. In the phase 2 portion, the primary objective was to evaluate the overall response rate (ORR) of CMP. In the phase 1 portion of the study, 24 patients received CMP at carfilzomib dosing levels of 20 mg/m(2), 27 mg/m(2), 36 mg/m(2), and 45 mg/m(2). The MTD was established as 36 mg/m(2). In the phase 2 portion of the study, 44 patients were enrolled at the MTD. Among 50 efficacy-evaluable patients treated at the MTD, the ORR was 90%. The projected 3-year overall survival rate was 80%. The combination of CMP was observed to be effective in elderly patients with newly diagnosed MM. This trial was registered at www.clinicaltrials.gov as #NCT01279694 (Eudract identifier 2010-019462-92).
authors.affiliation: Hematology Department, University Hospital Hôtel-Dieu, Nantes, France;
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.affiliation: Hematology Department, University Hospital, Reims, France;
authors.forename: Brigitte
authors.initials: B
authors.lastname: Kolb
authors.affiliation: Hematology Department, University Hospital, Toulouse, France;
authors.forename: Michel
authors.initials: M
authors.lastname: Attal
authors.affiliation: Hematology Department, University Hospital, Dijon, France;
authors.forename: Denis
authors.initials: D
authors.lastname: Caillot
authors.affiliation: Hematology Department, University Hospital, Tours, France;
authors.forename: Lotfi
authors.initials: L
authors.lastname: Benboubker
authors.affiliation: Hematology Department, University Hospital, La Roche sur Yon, France;
authors.forename: Mourad
authors.initials: M
authors.lastname: Tiab
authors.affiliation: Hematology Department, University Hospital Hôtel-Dieu, Nantes, France;
authors.forename: Cyrille
authors.initials: C
authors.lastname: Touzeau
authors.affiliation: Hematology Department, University Hospital, Lille, France;
authors.forename: Xavier
authors.initials: X
authors.lastname: Leleu
authors.affiliation: Hematology Department, University Hospital, Toulouse, France;
authors.forename: Murielle
authors.initials: M
authors.lastname: Roussel
authors.affiliation: Hematology Department, University Hospital, Clermont-Ferrand, France;
authors.forename: Carine
authors.initials: C
authors.lastname: Chaleteix
authors.affiliation: Hematology Department, University Hospital Hôtel-Dieu, Nantes, France;
authors.forename: Lucie
authors.initials: L
authors.lastname: Planche
authors.affiliation: Hematology Department, University Hospital Hôtel-Dieu, Nantes, France;
authors.forename: Anne
authors.initials: A
authors.lastname: Chiffoleau
authors.affiliation: Hematology Department, University Hospital Hôtel-Dieu, Nantes, France;
authors.forename: June
authors.initials: J
authors.lastname: Fortin
authors.affiliation: Hematology Department, University Hospital, Toulouse, France;
authors.forename: Hervé
authors.initials: H
authors.lastname: Avet-Loiseau
authors.affiliation: Inserm U1153, University Hospital Saint-Louis, Paris, France; and.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Mary
authors.affiliation: Hematology Department, University Hospital, Nancy, France.
authors.forename: Cyrille
authors.initials: C
authors.lastname: Hulin
authors.affiliation: Hematology Department, University Hospital, Lille, France;
authors.forename: Thierry
authors.initials: T
authors.lastname: Facon
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D009367:Neoplasm Staging; D009842:Oligopeptides / Q000008:administration & dosage; D011241:Prednisone / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D009842:Oligopeptides; C524865:carfilzomib; D008558:Melphalan; D011241:Prednisone