Phase 2 Study of the Safety and Pharmacokinetics of Carfilzomib in Subjects With Relapsed and Refractory Multiple Myeloma and Varying Degrees of Renal Function

Amgen5 sites in 1 country50 target enrollmentNovember 2008

ConditionsMultiple Myeloma Renal Insufficiency

InterventionsCarfilzomib

DrugsCarfilzomib

Overview

Phase: Phase 2
Intervention: Carfilzomib
Conditions: Multiple Myeloma
Sponsor: Amgen
Enrollment: 50
Locations: 5
Primary Endpoint: Clearance (CL) of Carfilzomib on Day 1 of Cycle 1
Status: Completed
Last Updated: 9 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to assess the influence of renal impairment on carfilzomib in patients with Multiple Myeloma (MM).

Registry

clinicaltrials.gov

Start Date

November 2008

End Date

November 2012

Last Updated

9 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Amgen

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Written informed consent in accordance with federal, local, and institutional guidelines
•Males and females ≥ 18 years of age
•Multiple Myeloma
•Documented relapsed or progressive disease (PD) after receiving at least two prior treatment regimens (induction therapy with autologous stem cell transplant and maintenance is considered a single regimen), and must have achieved a minimal response or better to at least one of the regimens
•Current measurable disease, as indicated by one or more of the following:
•Serum M-protein ≥ 0.5 g/dL
•Urine M-protein ≥ 200 mg/24 hours
•Serum Free Light Chain (FLC) assay: Involved FLC level ≥ 10 mg/dL provided serum FLC ratio is abnormal
•Life expectancy of more than three months
•Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2

Exclusion Criteria

•Glucocorticoid therapy in a dose equivalent to prednisone ≥ 20 mg/day within 14 days prior to first dose of study drug
•POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
•Plasma cell leukemia
•Chemotherapy with approved or investigative anticancer therapeutics, including steroid therapy dose as defined above, within 14 days prior to first dose of study drug or antibody therapy within 6 weeks prior to first dose of study drug
•Radiation therapy or immunotherapy within 3 weeks prior to first dose; localized radiation therapy within 1 week prior to first dose
•Participation in an investigational therapeutic study within 14 days prior to first dose of study drug
•Prior carfilzomib treatment
•Pregnant or lactating females
•Major surgery within 3 weeks prior to first dose of study drug
•Congestive heart failure (New York Heart Association Class III to IV), symptomatic ischemia, conduction abnormalities or myocardial infarction in the three months prior to first dose of study drug

Arms & Interventions

Carfilzomib

Carfilzomib, 15 mg/m², was administered intravenously (IV) on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles. If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.

Intervention: Carfilzomib

Outcomes

Primary Outcomes

Clearance (CL) of Carfilzomib on Day 1 of Cycle 1

Time Frame: Cycle 1, Day 1 before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.

Plasma concentrations of carfilzomib was determined by a validated liquid chromatography tandem mass spectrometry (LC MS/MS) method. The lower limit of quantitation (LLOQ) was 0.300 ng/mL. Concentration values that were below the LLOQ (BLQ) were set to zero. Pharmacokinetic (PK) parameters were calculated from the individual plasma concentrations of carfilzomib using a noncompartmental method.

Secondary Outcomes

Percentage of Carfilzomib Excreted Via Renal Elimination on Day 1 of Cycle 1(Cycle 1, Day 1, 0-5 and 5-24 hours post-dose)
Plasma Protein Binding (PPB) of Carfilzomib(End of injection and 5 minutes post-dose on Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 15)
Time to Progression (TTP)(Participants were followed for disease progression for up to 2 years.)
Area Under the Plasma Curve Extrapolated to Infinity (AUCinf) for Carfilzomib on Day 1 of Cycle 1(Cycle 1, Day 1, before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.)
Area Under the Concentration Time Curve to the Last Measurable Concentration (AUClast) for Carfilzomib on Day 15 of Cycle 2(Cycle 2, Day 15 before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.)
Maximum Observed Plasma Concentration of Carfilzomib on Day 1 of Cycle 1(Cycle 1, Day 1, before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.)
Maximum Observed Plasma Concentration of Carfilzomib on Day 15 of Cycle 2(Cycle 2, Day 15 before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.)
Area Under the Plasma Curve Extrapolated to Infinity (AUCinf) for Carfilzomib on Day 15 of Cycle 1(Cycle 1, Day 15 before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.)
Percentage of Carfilzomib Excreted Via Renal Elimination on Day 15 of Cycle 1(Cycle 1, Day 15, 0-5 and 5-24 hours post-dose)
Overall Response Rate (ORR)(From first dose until 30 days after the last dose; median duration of treatment across all groups was 121 days.)
Area Under the Concentration Time Curve to the Last Measurable Concentration (AUClast) for Carfilzomib on Day 15 of Cycle 1(Cycle 1, Day 15 before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.)
Percentage of Carfilzomib Metabolites Excreted Via Renal Elimination on Day 15 of Cycle 1(Cycle 1, Day 15, 0-5 and 5-24 hours post-dose)
Clearance (CL) of Carfilzomib on Day 15 of Cycle 1(Cycle 1, Day 15 before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.)
Clearance (CL) of Carfilzomib on Day 15 of Cycle 2(Cycle 2, Day 15, before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.)
Maximum Observed Plasma Concentration of Carfilzomib on Day 15 of Cycle 1(Cycle 1, Day 15 before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.)
Area Under the Plasma Curve Extrapolated to Infinity (AUCinf) for Carfilzomib on Day 15 of Cycle 2(Cycle 2, Day 15 before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.)
Area Under the Concentration Time Curve to the Last Measurable Concentration (AUClast) for Carfilzomib on Day 1 of Cycle 1(Cycle 1, Day 1 before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.)
Percentage of Carfilzomib Metabolites Excreted Via Renal Elimination on Day 1 of Cycle 1(Cycle 1, Day 1, 0-5 and 5-24 hours post-dose)
Clinical Benefit Rate (CBR)(From first dose until 30 days after the last dose; median duration of treatment across all groups was 121 days.)
Duration of Response(Participants were followed for disease progression for up to 2 years.)