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

NCT01949532 | Completed Phase 1 Results

• 2 other identifiers: CFZ00120130401
• Study Type: interventional
• Target: 26
• Locations: 3 countries
• Sites: 13

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.

Conditions

Relapsed Multiple Myeloma; End-stage Renal Disease

Outcome Measures

Primary Outcomes (2)

• 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.

• 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

  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 Outcomes (30)

• 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.

• 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.

• 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.

• 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.

• 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.

Study Arms (2)

Normal Renal Function

EXPERIMENTAL

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.

Drug: Carfilzomib

End Stage Renal Disease

EXPERIMENTAL

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.

Drug: Carfilzomib

Interventions

Carfilzomib DRUG

Carfilzomib was administered by IV injection.

Also known as: Kyprolis®

End Stage Renal Disease; Normal Renal Function

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Relapsed multiple myeloma
• Evaluable disease (serum protein electrophoresis \[SPEP\]/urine protein electrophoresis \[UPEP\]/serum free light chain \[SFLC\] criteria)
• Received at least 1 prior treatment regimen or line of therapy for multiple myeloma
• End-stage renal disease (ESRD) on hemodialysis or CrCl ≥ 75 mL/min
• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2
• Adequate organ and bone marrow function
• 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

You may not qualify if:

• Immunoglobulin M (IgM) multiple myeloma
• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Waldenström Macroglobulinemia
• Active congestive heart failure (NYHA Class III-IV) ischemia, conduction abnormalities
• Known human immunodeficiency virus (HIV), recent hepatitis B virus (HBV), hepatitis C virus (HCV)
• Myelodysplastic Syndrome
• Contraindication to test article, constituents, or required concomitant medications
• Other investigational drugs

Sponsors & Collaborators

• Amgen: lead

Study Sites (13)

Karmanos Cancer Institute

Detroit, Michigan, United States

Location

North Shore-LIJ Health System/Center for Advanced Medicine - North Shore University Hospital

Lake Success, New York, United States

Location

Gabrail Cancer Center

Canton, Ohio, United States

Location

Vanderbilt-Ingram Cancer Center, Henry-Joyce Cancer Clinic

Nashville, Tennessee, United States

Location

Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States

Location

UT Southwestern Medical Center

Dallas, Texas, United States

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Location

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

Location

Monash Health, Monash Medical Centre

Clayton, Victoria, Australia

Location

St. Vincent's Hospital Melbourne

Fitzroy, Victoria, Australia

Location

The Alfred Hospital, Malignant Haematology and Stem Cell Transplant Department

Melbourne, Victoria, Australia

Location

QEII Health Sciences Centre

Halifax, Nova Scotia, Canada

Location

Sir Mortimer B. Davis-Jewish General Hospital

Montreal, Quebec, Canada

Location

MeSH Terms

Conditions

Multiple Myeloma; Kidney Failure, Chronic

Interventions

carfilzomib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Amgen, Inc.

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2013
• First Posted: September 24, 2013
• Study Start: January 1, 2014
• Primary Completion: April 1, 2015
• Study Completion: January 1, 2017
• Last Updated: May 2, 2017
• Results First Posted: May 4, 2016

Record last verified: 2017-04

Locations

US (6); CA (2); AU (5)