Study of the Pharmacokinetics and Safety of Carfilzomib in Patients With Multiple Myeloma and Renal Disease

End-stage Renal Disease Clinical Trial

Official title:

An Open-Label, Single Arm, Phase 1 Study of the Pharmacokinetics and Safety of Carfilzomib in Subjects With Relapsed Multiple Myeloma and End-stage Renal Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01949532
• Other study ID #: CFZ001
• Secondary ID: 20130401
• Status: Completed
• Phase: Phase 1
• First received: September 6, 2013
• Last updated: April 28, 2017
• Start date: January 2014
• Est. completion date: January 2017

Study information

• Verified date: April 2017
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: January 2017
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

1. Relapsed multiple myeloma

2. Evaluable disease (serum protein electrophoresis [SPEP]/urine protein electrophoresis [UPEP]/serum free light chain [SFLC] criteria)

3. Received at least 1 prior treatment regimen or line of therapy for multiple myeloma

4. End-stage renal disease (ESRD) on hemodialysis or CrCl = 75 mL/min

5. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2

6. Adequate organ and bone marrow function

7. Active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention or myocardial infarction within the protocol-specified period prior to enrollment

Key Exclusion Criteria:

1. Immunoglobulin M (IgM) multiple myeloma

2. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)

3. Waldenström Macroglobulinemia

4. Active congestive heart failure (NYHA Class III-IV) ischemia, conduction abnormalities

5. Known human immunodeficiency virus (HIV), recent hepatitis B virus (HBV), hepatitis C virus (HCV)

6. Myelodysplastic Syndrome

7. Contraindication to test article, constituents, or required concomitant medications

8. Other investigational drugs

Related Conditions & MeSH terms

• End-stage Renal Disease
• Kidney Diseases
• Kidney Failure, Chronic
• Multiple Myeloma
• Neoplasms, Plasma Cell
• Relapsed Multiple Myeloma
• Renal Insufficiency, Chronic

Intervention

Drug:
• Carfilzomib
Carfilzomib was administered by IV injection.

Locations

Country	Name	City	State
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Monash Health, Monash Medical Centre	Clayton	Victoria
Australia	St. Vincent's Hospital Melbourne	Fitzroy	Victoria
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	The Alfred Hospital, Malignant Haematology and Stem Cell Transplant Department	Melbourne	Victoria
Canada	QEII Health Sciences Centre	Halifax	Nova Scotia
Canada	Sir Mortimer B. Davis-Jewish General Hospital	Montreal	Quebec
United States	Gabrail Cancer Center	Canton	Ohio
United States	Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	UT Southwestern Medical Center	Dallas	Texas
United States	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	Vanderbilt-Ingram Cancer Center, Henry-Joyce Cancer Clinic	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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.
Primary	Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-8) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2		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.
Secondary	Maximum Observed Plasma Concentration (Cmax) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2		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.
Secondary	Time to Maximum Observed Plasma Concentration (Tmax) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2		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.
Secondary	Terminal Half-life (T½) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2		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.
Secondary	Clearance (CL) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2		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.
Secondary	Mean Residence Time (MRT) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2		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.
Secondary	Volume of Distribution at Steady State (Vss) of Carfilzomib Following 56 mg/m² Carfilzomib on Day 1 of Cycle 2		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.
Secondary	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		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.
Secondary	Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-8) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1		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.
Secondary	Maximum Observed Plasma Concentration (Cmax) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1		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.
Secondary	Time to Maximum Observed Plasma Concentration (Tmax) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1		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.
Secondary	Terminal Half-life (T½) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1		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.
Secondary	Clearance (CL) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1		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.
Secondary	Mean Residence Time (MRT) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1		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.
Secondary	Volume of Distribution at Steady State (Vss) of Carfilzomib Following 27 mg/m² Carfilzomib on Day 16 of Cycle 1		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.
Secondary	Area Under the Concentration Time Curve From Time 0 to Last Concentration (AUC0-last) for Metabolite PR-389/M14		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.
Secondary	Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-8) for Metabolite PR-389/M14		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.
Secondary	Maximum Observed Plasma Concentration for Metabolite PR-389/M14		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.
Secondary	Time to Maximum Observed Plasma Concentration (Tmax) for Metabolite PR-389/M14		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.
Secondary	Terminal Half-life (T½) of Metabolite PR-389/M14		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.
Secondary	Area Under the Concentration Time Curve From Time 0 to Last Concentration (AUC0-last) for Metabolite PR-413/M15		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.
Secondary	Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-8) for Metabolite PR-413/M15		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.
Secondary	Maximum Observed Plasma Concentration (Cmax) for Metabolite PR-413/M15		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.
Secondary	Time to Maximum Observed Plasma Concentration (Tmax) for Metabolite PR-413/M15		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.
Secondary	Terminal Half-life (T½) of Metabolite PR-413/M15		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.
Secondary	Area Under the Concentration Time Curve From Time 0 to Last Concentration (AUC0-last) for Metabolite PR-519/M16		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.
Secondary	Area Under the Concentration Time Curve From Time 0 Extrapolated to Infinity (AUC0-8) for Metabolite PR-519/M16		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.
Secondary	Maximum Observed Plasma Concentration (Cmax) for Metabolite PR-519/M16		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.
Secondary	Time to Maximum Observed Plasma Concentration (Tmax) for Metabolite PR-519/M16		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.
Secondary	Terminal Half-life (T½) of Metabolite PR-519/M16		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.
Secondary	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.	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.