The purpose of this study is to see how the body and the cancer react to carfilzomib, including measuring the amount of the study drug in the blood at certain times following dosing. This study is being done in people with normal kidney function and those with end-stage renal disease to see if they respond differently to the study drug.
Specifically, the purpose of this study is to assess the influence of end-stage renal disease (ESRD) on area under the curve (both area under the curve, from time 0 to the last concentration measured \[AUC0-last\] and area under the curve, from time 0 extrapolated to infinity \[AUC0-inf\]) of carfilzomib 56 mg/m² at Cycle 2 Day 1 (C2D1) in patients with relapsed multiple myeloma.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
26
Carfilzomib was administered by IV injection.
Karmanos Cancer Institute
Detroit, Michigan, United States
North Shore-LIJ Health System/Center for Advanced Medicine - North Shore University Hospital
Lake Success, New York, United States
Gabrail Cancer Center
Area Under the Concentration Time Curve From Time 0 to Last Concentration (AUC0-last) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2
Carfilzomib plasma concentrations for pharmacokinetic (PK) analyses were measured by liquid chromatography with tandem mass spectrometry. The lower limit of quantitation (LLOQ) for the assay was 0.3 ng/mL.
Time frame: Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2
Time frame: Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Maximum Observed Plasma Concentration (Cmax) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2
Time frame: Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Time to Maximum Observed Plasma Concentration (Tmax) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2
Time frame: Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Terminal Half-life (T½) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2
Time frame: Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
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Canton, Ohio, United States
Vanderbilt-Ingram Cancer Center, Henry-Joyce Cancer Clinic
Nashville, Tennessee, United States
Baylor Charles A. Sammons Cancer Center
Dallas, Texas, United States
UT Southwestern Medical Center
Dallas, Texas, United States
Royal Prince Alfred Hospital
Camperdown, New South Wales, Australia
Royal Brisbane and Women's Hospital
Herston, Queensland, Australia
Monash Health, Monash Medical Centre
Clayton, Victoria, Australia
St. Vincent's Hospital Melbourne
Fitzroy, Victoria, Australia
...and 3 more locations
Clearance (CL) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2
Time frame: Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Mean Residence Time (MRT) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2
Time frame: Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Volume of Distribution at Steady State (Vss) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2
Time frame: Cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Area Under the Concentration Time Curve From Time 0 to Last Concentration (AUC0-last) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1
Time frame: Cycle 1, day 16 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1
Time frame: Cycle 1, day 16 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Maximum Observed Plasma Concentration (Cmax) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1
Time frame: Cycle 1, day 16 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Time to Maximum Observed Plasma Concentration (Tmax) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1
Time frame: Cycle 1, day 16 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Terminal Half-life (T½) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1
Time frame: Cycle 1, day 16 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Clearance (CL) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1
Time frame: Cycle 1, day 16 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Mean Residence Time (MRT) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1
Time frame: Cycle 1, day 16 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Volume of Distribution at Steady State (Vss) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1
Time frame: Cycle 1, day 16 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Area Under the Concentration Time Curve From Time 0 to Last Concentration (AUC0-last) for Metabolite PR-389/M14
Time frame: Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) for Metabolite PR-389/M14
Time frame: Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Maximum Observed Plasma Concentration for Metabolite PR-389/M14
Time frame: Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Time to Maximum Observed Plasma Concentration (Tmax) for Metabolite PR-389/M14
Time frame: Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Terminal Half-life (T½) of Metabolite PR-389/M14
Time frame: Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Area Under the Concentration Time Curve From Time 0 to Last Concentration (AUC0-last) for Metabolite PR-413/M15
Time frame: Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) for Metabolite PR-413/M15
Time frame: Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Maximum Observed Plasma Concentration (Cmax) for Metabolite PR-413/M15
Time frame: Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Time to Maximum Observed Plasma Concentration (Tmax) for Metabolite PR-413/M15
Time frame: Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Terminal Half-life (T½) of Metabolite PR-413/M15
Time frame: Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Area Under the Concentration Time Curve From Time 0 to Last Concentration (AUC0-last) for Metabolite PR-519/M16
Time frame: Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) for Metabolite PR-519/M16
Time frame: Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Maximum Observed Plasma Concentration (Cmax) for Metabolite PR-519/M16
Time frame: Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Time to Maximum Observed Plasma Concentration (Tmax) for Metabolite PR-519/M16
Time frame: Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Terminal Half-life (T½) of Metabolite PR-519/M16
Time frame: Cycle 1, day 16 and cycle 2, day 1 at predose, 15 minutes post start of infusion, immediately before the end of infusion, and at 5, 15, and 30 minutes, and 1, 2, and 4 hours after the end of the infusion.
Number of Participants With Adverse Events (AEs)
Determination of the severity of all adverse events was assessed following the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 4.03, where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Fatal. A Serious AE is an AE that meets one or more of the following criteria: * Death, * Life-threatening experience; * Requires in-patient hospitalization or prolongation of an existing hospitalization, * Results in persistent or significant disability/incapacity, * Is a congenital anomaly/birth defect, * Important medical events that may not result in death, be life-threatening, or require hospitalization. Treatment-related adverse events (TRAEs) are adverse events considered related to carfilzomib by the investigator, including those with unknown relationship.
Time frame: From the first dose of study drug up to 30 days after the last dose of study drug as of the data cut-off date of 12 October 2015; median duration of treatment was 14 weeks in the normal renal function group and 12 weeks in the ESRD group.