Phase I/II study of carfilzomib plus melphalan and prednisone in patients aged over 65 years with newly diagnosed multiple myeloma
Mené sur 24 et 44 patients atteints d'un myélome multiple récemment diagnostiqué (âge supérieur à 65 ans), cet essai de phase I/II évalue la dose maximale tolérée du carfilzomib, puis l'efficacité, du point de vue du taux de réponse globale, et la toxicité d'un traitement combinant carfilzomib, melphalan et prednisone
This phase I/II 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 1–4; carfilzomib was administered intravenously on days 1, 2, 8, 9, 22, 23, 29, and 30 of a 42-day cycle. Patients received up to nine cycles of CMP. In the phase I, 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 II portion, the primary objective was to evaluate the overall response rate (ORR) of CMP. In the phase I portion of the study, 24 patients received CMP at carfilzomib dosing levels of 20 mg/m2, 27 mg/m2, 36 mg/m2, and 45 mg/m2. The MTD was established as 36 mg/m2. In the phase II 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. www.clinicaltrials.gov identifier NCT01279694, Eudract identifier 2010-019462-92