CHAMPION-1: a phase 1/2 study of weekly carfilzomib and dexamethasone for relapsed or relapsed and refractory multiple myeloma
Mené sur 116 patients atteints d'un myélome multiple récidivant/réfractaire, cet essai de phase I/II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité d'un traitement combinant carfilzomib et dexaméthasone
The CHAMPION-1 study is the first clinical trial to investigate carfilzomib on a once-weekly dosing schedule with dexamethasone.Once-weekly carfilzomib (30-min infusion; 20/70 mg/m2) with dexamethasone is feasible and effective in relapsed or relapsed and refractory MM. Carfilzomib, a proteasome inhibitor, is approved in the United States as a single agent for relapsed or refractory multiple myeloma (RRMM) and in combination with dexamethasone or lenalidomide/dexamethasone (KRd) for RRMM. Under the single-agent and KRd approvals, carfilzomib is administered as a 10 minute intravenous infusion on days 1, 2, 8, 9, 15, and 16 of 28-day cycles (starting dose: 20 mg/m2 [cycle 1, days 1-2]; target dose: 27 mg/m2 thereafter). This multicenter, single-arm, phase 1/2 study, CHAMPION-1, evaluated the safety and efficacy of once weekly carfilzomib with dexamethasone in relapsed or relapsed and refractory MM (1-3 prior therapies). Patients received carfilzomib as a 30-minute intravenous infusion on days 1, 8, and 15 of 28 day cycles. The phase 1 portion utilized a 3+3 dose-escalation scheme to determine the maximum tolerated dose (MTD) of carfilzomib. In the phase 2 portion, patients received carfilzomib on the same schedule at the MTD. Patients received dexamethasone (40 mg) on days 1, 8, 15, and 22; dexamethasone was omitted on day 22 starting with cycle 9. One hundred and sixteen patients were enrolled. The MTD was 70 mg/m2, and 104 patients (phase 1 and 2) received carfilzomib at this dose. At 70 mg/m2, the median number of prior regimens was 1; 52% were bortezomib-refractory. At the MTD, the most common grade ≥3 adverse events were fatigue (11%) and hypertension (7%). Overall response rate at the MTD was 77%. Median progression-free survival was 12.6 months. These findings merit additional evaluation of the once-weekly dosing regimen. This trial was registered at www.clinicaltrials.gov as NCT01677858.