title: CHAMPION-1: a phase 1/2 study of once-weekly carfilzomib and dexamethasone for relapsed or refractory multiple myeloma.
abstract: 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/m(2) [cycle 1, days 1-2]; 27 mg/m(2) 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/m(2), and 104 patients (phase 1/2) received carfilzomib 70 mg/m(2) At 70 mg/m(2), the median number of prior regimens was 1; and 52% were bortezomib-refractory. At 70 mg/m(2), the most common grade ≥3 adverse events were fatigue (11%) and hypertension (7%). Overall response rate at 70 mg/m(2) 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.
authors.affiliation: Institute for Myeloma and Bone Cancer Research, West Hollywood, CA;
authors.forename: James R
authors.initials: JR
authors.lastname: Berenson
authors.affiliation: Comprehensive Blood and Cancer Center, Bakersfield, CA;
authors.forename: Alan
authors.initials: A
authors.lastname: Cartmell
authors.affiliation: Cancer Care Associates for Research and Excellence, Encinitas, CA;
authors.forename: Alberto
authors.initials: A
authors.lastname: Bessudo
authors.affiliation: US Oncology Research and Cancer Care Centers of South Texas, San Antonio, TX;
authors.forename: Roger M
authors.initials: RM
authors.lastname: Lyons
authors.affiliation: Horizon Oncology Center, Lafayette, IN;
authors.forename: Wael
authors.initials: W
authors.lastname: Harb
authors.affiliation: Cedars-Sinai Medical Center, Los Angeles, CA;
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Tzachanis
authors.affiliation: The Oncology Institute of Hope and Innovation, Downey, CA;
authors.forename: Richy
authors.initials: R
authors.lastname: Agajanian
authors.affiliation: Center for Cancer and Blood Disorders, Bethesda, MD;
authors.forename: Ralph
authors.initials: R
authors.lastname: Boccia
authors.affiliation: Department of Hematology/Oncology, Weill Cornell Medical College, Clinical Research Alliance, New Hyde Park, NY;
authors.forename: Morton
authors.initials: M
authors.lastname: Coleman
authors.affiliation: Robert A. Moss Medical Oncology and Hematology, Fountain Valley, CA;
authors.forename: Robert A
authors.initials: RA
authors.lastname: Moss
authors.affiliation: US Oncology Research and Rocky Mountain Cancer Centers, Denver, CO;
authors.forename: Robert M
authors.initials: RM
authors.lastname: Rifkin
authors.affiliation: Onyx Pharmaceuticals, Inc., an Amgen subsidiary, South San Francisco, CA; and.
authors.forename: Priti
authors.initials: P
authors.lastname: Patel
authors.affiliation: Onyx Pharmaceuticals, Inc., an Amgen subsidiary, South San Francisco, CA; and.
authors.forename: Sandra
authors.initials: S
authors.lastname: Dixon
authors.affiliation: Onyx Pharmaceuticals, Inc., an Amgen subsidiary, South San Francisco, CA; and.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ou
authors.affiliation: Onyx Pharmaceuticals, Inc., an Amgen subsidiary, South San Francisco, CA; and.
authors.forename: Janet
authors.initials: J
authors.lastname: Anderl
authors.affiliation: Onyx Pharmaceuticals, Inc., an Amgen subsidiary, South San Francisco, CA; and.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Aggarwal
authors.affiliation: Sarah Cannon Research Institute, Nashville, TN.
authors.forename: Jesus G
authors.initials: JG
authors.lastname: Berdeja
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality*; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects; D012008:Recurrence; D015996:Survival Rate
chemical_list: D009842:Oligopeptides; C524865:carfilzomib; D003907:Dexamethasone