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

NCT00721734 | Completed Phase 2 Results

• 1 other identifier: PX-171-005
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 5

Brief Summary

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

Conditions

Multiple Myeloma; Renal Insufficiency

Keywords

Myeloma; Renal Insufficiency; Proteasome; Hematological; carfilzomib; PR-171

Outcome Measures

Primary Outcomes (1)

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

  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.

  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.

Secondary Outcomes (20)

• 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 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 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.

• 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.

Study Arms (1)

Carfilzomib

EXPERIMENTAL

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.

Drug: Carfilzomib

Interventions

Carfilzomib DRUG

Carfilzomib was administered intravenously (IV) at a rate of approximately 10 mL/minute.

Also known as: PR-171, Kyprolis®

Carfilzomib

Eligibility Criteria

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

You may qualify if:

• 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
• Adequate hepatic function, with bilirubin \< 2 times the upper limit of normal (ULN) and alanine aminotransferase (ALT) \< 3 times ULN
• Total white blood cell (WBC) count ≥ 2,000/mm³
• Absolute neutrophil count (ANC) ≥ 1,000/mm³
• Hemoglobin ≥ 7 gm/dL
• Subjects may receive red blood cell (RBC) transfusions or supportive care with erythropoietin or darbepoetin in accordance with institutional guidelines

You may not qualify if:

• 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
• Uncontrolled hypertension
• Recent history of acute active infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose of study drug
• Known or suspected human immunodeficiency virus (HIV) infection, known HIV seropositivity
• Active hepatitis A, B, or C infection
• Other malignancy within the past 3 years except a) adequately treated basal cell or squamous cell skin cancer, b) carcinoma in situ of the cervix, or c) prostate cancer \< Gleason Grade 7 with stable prostate specific antigen (PSA) levels

Sponsors & Collaborators

• Amgen: lead

Study Sites (5)

University of California- San Francisco

San Francisco, California, 94143, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Cornell University

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Renal Insufficiency; Neoplasms, Plasma Cell

Interventions

carfilzomib

Condition Hierarchy (Ancestors)

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; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

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 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2008
• First Posted: July 24, 2008
• Study Start: November 1, 2008
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: May 2, 2017
• Results First Posted: December 9, 2015

Record last verified: 2017-04

Locations

US (5)