Details

Autor(en) / Beteiligte

• Berenson, James R.
• Cartmell, Alan
• Bessudo, Alberto
• Lyons, Roger M.
• Harb, Wael
• Tzachanis, Dimitrios
• Agajanian, Richy
• Boccia, Ralph
• Coleman, Morton
• Moss, Robert A.
• Rifkin, Robert M.
• Patel, Priti
• Dixon, Sandra
• Ou, Ying
• Anderl, Janet
• Aggarwal, Sanjay
• Berdeja, Jesus G.

Titel

CHAMPION-1: a phase 1/2 study of once-weekly carfilzomib and dexamethasone for relapsed or refractory multiple myeloma

Ist Teil von

• Blood, 2016-06, Vol.127 (26), p.3360-3368

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2016

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Carfilzomib, a proteasome inhibitor, is approved in the United States as a single agent, and in combination with dexamethasone or lenalidomide/dexamethasone (KRd) for relapsed or refractory multiple myeloma (MM). Under the single-agent and KRd approvals, carfilzomib is administered as a 10-minute IV infusion on days 1, 2, 8, 9, 15, and 16 of 28-day cycles (20 mg/m2 [cycle 1, days 1-2]; 27 mg/m2 thereafter). This multicenter, single-arm, phase 1/2 study, Community Harmonized Assessment of Myeloma Patients via an Integrated Oncology Network-1 (CHAMPION-1), evaluated once-weekly carfilzomib with dexamethasone in relapsed, or relapsed and refractory MM (1-3 prior therapies). Patients received carfilzomib (30-minute IV infusion) on days 1, 8, and 15 of 28-day cycles. The phase 1 portion used a 3 + 3 dose-escalation scheme to determine the maximum tolerated dose (MTD) of carfilzomib. During phase 2, 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 for cycles 9+. A total of 116 patients were enrolled. The MTD was 70 mg/m2, and 104 patients (phase 1/2) received carfilzomib 70 mg/m2. At 70 mg/m2, the median number of prior regimens was 1; and 52% were bortezomib-refractory. At 70 mg/m2, the most common grade ≥3 adverse events were fatigue (11%) and hypertension (7%). Overall response rate at 70 mg/m2 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. •The CHAMPION-1 study is the first clinical trial to investigate carfilzomib on a once-weekly dosing schedule with dexamethasone.•Once-weekly carfilzomib (30-minute infusion; 20 and 70 mg/m2) with dexamethasone is feasible and effective in relapsed/refractory MM.