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Trial record 13 of 21 for:    stem cell kidney | ( Map: Canada )

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01949532
Recruitment Status : Completed
First Posted : September 24, 2013
Results First Posted : May 4, 2016
Last Update Posted : May 2, 2017
Sponsor:
Information provided by (Responsible Party):
Amgen

Tracking Information
First Submitted Date  ICMJE September 6, 2013
First Posted Date  ICMJE September 24, 2013
Results First Submitted Date  ICMJE March 31, 2016
Results First Posted Date  ICMJE May 4, 2016
Last Update Posted Date May 2, 2017
Study Start Date  ICMJE January 2014
Actual Primary Completion Date April 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 31, 2016)
  • 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 [ 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. ]
    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.
  • 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. ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 19, 2013)
Influence of End-stage Renal Disease on Area Under the Curve [ Time Frame: Cycle 2 Day 1 ]
The primary endpoints are the 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 C2D1
Change History Complete list of historical versions of study NCT01949532 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 31, 2016)
  • 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. ]
  • 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) [ 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. ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 19, 2013)
  • Influence of End-stage Renal Disease on Additional Pharmacokinetics (PK) Parameters of Carfilzomib 56 mg/m2 at Cycle 2 Day 1 (C2D1) [ Time Frame: Cycle 2 Day 1 ]
    Pharmacokinetics (PK) parameters comparison between subject cohorts of carfilzomib 56 mg/m2 at Cycle 2 Day 1 (C2D1), including maximum plasma concentration (Cmax), time to maximum concentration (tmax), clearance (CL), terminal half-life (t1/2), volume of distribution at steady state (Vss), and mean residence time (MRT)
  • Influence of End-stage Renal Disease on Additional Pharmacokinetics (PK) Parameters of Carfilzomib 27 mg/m2 [ Time Frame: Cycle 1 Day 16 ]
    Pharmacokinetics (PK) parameters comparison between subject cohorts of carfilzomib 27 mg/m2 at Cycle 1 Day 16 (C1D16), including AUC0-last, AUC0-inf, Cmax, tmax, CL, t1/2, Vss, and MRT
  • Influence of End-stage Renal Disease on Additional Pharmacokinetics (PK) parameters for major metabolites [ Time Frame: Cycle 1 Day 16 and Cycle 2 Day 1 ]
    Evaluation of pharmacokinetics (PK) parameters for major metabolites (metabolites PR-389/M14, PR-413/M15, and PR-519/M16) at Cycle 1 Day 16 (C1D16) (27 mg/m2) and Cycle 2 Day 1 (C2D1) (56 mg/m2) including AUC0-last, AUC0-inf, Cmax, tmax, t1/2, and MRT
  • Safety and Tolerability [ Time Frame: 24 months ]
    Safety and tolerability of carfilzomib: Incidence, severity and causal relationship for all adverse events (AEs) (including serious adverse events [SAEs]); incidence of laboratory shifts for key analytes to and from limits of normal range; and Common Terminology Criteria for Adverse events (CTCAE) Grade relative to baseline in key laboratory parameters
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: September 19, 2013)
  • Exploratory Objectives: Best Overall Response Rate (ORR) [ Time Frame: 36 months ]
    Each evaluable subject's response (frequency and proportion) to treatment over the course of the study will be evaluated by the investigator according to the International Myeloma Working Group (IMWG) response criteria. Best overall response rate (ORR) is defined as partial response (PR) or better.
  • Exploratory Objectives: Clinical Benefit Response (CBR) [ Time Frame: 36 months ]
    Each evaluable subject's response (frequency and proportion) to treatment over the course of the study will be evaluated by the investigator according to the International Myeloma Working Group (IMWG) response criteria. Clinical Benefit Response (CBR) is defined as ORR + minimal response (MR).
  • Exploratory Objectives: Duration of Response (DOR) [ Time Frame: 36 months ]
    Duration of response will be defined as the time from first evidence of partial response (PR) or better to confirmation of progressive disease (PD).
  • Exploratory Objectives: Progression-Free Survival (PFS) [ Time Frame: 36 months ]
    Progression-free survival (PFS) will be defined as the time from the beginning of treatment to progressive disease (PD) or death.
 
Descriptive Information
Brief Title  ICMJE Study of the Pharmacokinetics and Safety of Carfilzomib in Patients With Multiple Myeloma and Renal Disease
Official Title  ICMJE 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
Brief 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.
Detailed 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE
  • Relapsed Multiple Myeloma
  • End-stage Renal Disease
Intervention  ICMJE Drug: Carfilzomib
Carfilzomib was administered by IV injection.
Other Name: Kyprolis®
Study Arms  ICMJE
  • Experimental: Normal Renal Function
    Participants with normal renal function (creatinine clearance [CrCl] ≥ 75 mL/min) received carfilzomib 20 mg/m² intravenous infusion (IV) on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles. Participants continued treatment until confirmed progressive disease, unacceptable toxicity, withdrawal of consent, study closure, or death.
    Intervention: Drug: Carfilzomib
  • Experimental: End Stage Renal Disease
    Participants with end-stage renal disease (on hemodialysis) received carfilzomib 20 mg/m² intravenous infusion (IV) on days 1 and 2 of cycle 1, followed by 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15 and 16 of cycle 2 and all subsequent cycles. Participants continued treatment until confirmed progressive disease, unacceptable toxicity, withdrawal of consent, study closure, or death.
    Intervention: Drug: Carfilzomib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 31, 2016)
26
Original Estimated Enrollment  ICMJE
 (submitted: September 19, 2013)
32
Actual Study Completion Date  ICMJE January 2017
Actual Primary Completion Date April 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Australia,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01949532
Other Study ID Numbers  ICMJE CFZ001
20130401 ( Other Identifier: Sponsor )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Amgen
Study Sponsor  ICMJE Amgen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: MD Amgen
PRS Account Amgen
Verification Date April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP