Phase 2 Study of Carfilzomib in Relapsed Multiple Myeloma

NCT00530816 | Completed Phase 2 Results

• 1 other identifier: PX-171-004
• Study Type: interventional
• Target: 164
• Locations: 2 countries
• Sites: 30

Brief Summary

To evaluate the best overall response rate, safety and tolerability of carfilzomib in patients with relapsed or refractory multiple myeloma.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Best Overall Response Rate (ORR) in the Response Evaluable Subset Population

  ORR is defined as the percentage of patients who achieved a best response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR) determined by Independent Review Committee (IRC). Responses were assessed according to International Uniform Response Criteria for Multiple Myeloma, documented by 2 consecutive assessments made at any time before the start of new therapy. sCR: CR as defined below plus normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence. CR: absence of M-protein in serum and urine by immunofixation, disappearance of any soft tissue plasmacytomas, and ≤5% plasma cells in bone marrow. VGPR: serum and urine M-proteins detectable by immunofixation but not by electrophoresis or a ≥ 90% reduction in serum M-protein with urine M-protein level \< 100 mg/24 hours. PR: ≥ 50% reduction of serum M-protein and in urine of ≥ 90% or to \< 200 mg per 24 hours.

  Disease response was assessed on Day 15 of Cycle 1, Day 1 of Cycles 2 through 12, and at End of Study, 30 days after last dose. Median duration of treatment was 100 days for Part 1 and 170 days for Part 2 participants.

Secondary Outcomes (6)

• Best Overall Response Rate (ORR) in the Response Evaluable Population

  Disease response was assessed on Day 15 of Cycle 1, Day 1 of Cycles 2 through 12, End of Study, 30 days after last dose; median duration of treatment was 100 days for Part 1 and 170 days for Part 2 participants.

• Clinical Benefit Rate (CBR)

  Disease response was assessed on Day 15 of Cycle 1, Day 1 of Cycles 2 through 12, and at End of Study, 30 days after last dose. Median duration of treatment was 100 days for Part 1 and 170 days for Part 2 participants.

• Duration of Response (DOR)

  Patients were followed for up to 2 years after study discontinuation. The data cutoff for the analysis is 30 November 2010 for Part 1 and 22 April 2011 for Part 2.

• Time to Progression (TTP)

  Patients were followed for up to 2 years after study discontinuation. The data cutoff for the analysis is 30 November 2010 for Part 1 and 22 April 2011 for Part 2. Median follow-up time was 13.4 months for Part 1 and 11.5 months in Part 2.

• Progression-free Survival (PFS)

  Patients were followed for up to 2 years after study discontinuation. The data cutoff for the analysis is 30 November 2010 for Part 1 and 22 April 2011 for Part 2. Median follow-up time was 13.4 months for Part 1 and 11.5 months in Part 2.

Study Arms (1)

Carfilzomib

EXPERIMENTAL

Participants received carfilzomib 20 mg/m² intravenous (IV) injection on Days 1, 2, 8, 9, 15, and 16, in 28-day treatment cycles for a maximum of 12 cycles. Starting with Amendment 3, if all doses in Cycle 1 were well-tolerated the dose was escalated to 27 mg/m² IV for subsequent cycles.

Drug: carfilzomib

Interventions

carfilzomib DRUG

Intravenous (IV) injection over 2 to 10 minutes twice weekly for three weeks followed by 12 days of rest.

Also known as: PR-171, PR171, Kyprolis® (carfilzomib) for Injection

Carfilzomib

Eligibility Criteria

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

You may qualify if:

• Disease Related
• Multiple myeloma
• Subjects must have measurable disease, defined as one or more of the following:
• Serum M-protein ≥ 1 g/dL
• Urine M-protein ≥ 200 mg/24 hours
• Subjects must have been responsive (i.e., achieve a minimal response \[MR\] or better) to standard, first line therapy
• Relapsed and/or refractory or progressive disease after at least one, but no more than three, prior therapeutic treatments or regimens for multiple myeloma. Refractory disease is defined as ≤ 25% response or progression during therapy or within 60 days after completion of therapy. Induction therapy and stem cell transplant will be considered as one regimen
• Demographic
• Males and females ≥18 years of age
• Life expectancy of more than three months
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
• Laboratory
• Adequate hepatic function, with bilirubin \< 2.0 times the upper limit of normal, and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of \< 3.0 times the upper limit of normal
• Uric acid, if elevated, must be corrected to within laboratory normal range prior to dosing
• Total white blood cell (WBC) count ≥ 2,000/mm³, absolute neutrophil count \> 1,000/mm³, hemoglobin ≥ 8.0 g/dL, and platelet count \> 50,000/mm³

You may not qualify if:

• Disease Related
• Multiple Myeloma Immunoglobulin M (IgM)
• Subjects previously treated with any proteasome inhibitor (for Part 2 Proteasome Inhibitor - Naïve only, criteria added at Amendment 2)
• Subjects must not be primary refractory to standard first-line therapy
• Subjects with non-secretory multiple myeloma, defined as \< 1 g/dL M-protein in serum, \< 200 mg/24 hour M-protein in urine
• Subjects with disease measurable only by serum free light chain (SFLC) analysis
• Glucocorticoid therapy (prednisone \>10 mg/day orally or equivalent) within the last three weeks
• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Plasma cell leukemia
• Chemotherapy with approved or investigative anticancer therapeutics, including steroid therapy, within the three weeks prior to first dose
• Radiation therapy or immunotherapy in the previous four weeks; localized radiation therapy within 1 week prior to first dose
• Participation in an investigational therapeutic study within three weeks or within five drug half-lives (t1/2) prior to first dose, whichever time is greater
• Prior treatment with carfilzomib
• Concurrent Conditions
• Major surgery within three weeks before Day 1

Sponsors & Collaborators

• Amgen: lead

Study Sites (30)

Mayo Clinic Scottsdale

Scottsdale, Arizona, 85259, United States

Location

Tower Cancer Research Foundation

Beverly Hills, California, 90211, United States

Location

Therapeutic Research Institute of Orange County

Laguna Hills, California, 92653, United States

Location

Rocky Mountain Blood and Marrow Transplant Program

Denver, Colorado, 80218, United States

Location

Oncology & Hematology Assoc. of W. Broward

Tamarac, Florida, 33321, United States

Location

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

Emory University Winship Cancer Institute

Atlanta, Georgia, 404-778-5747, United States

Location

Northwestern University

Chicago, Illinois, 60605, United States

Location

Orchard Research

Skokie, Illinois, 60076, United States

Location

University of Kentucky College of Medicine

Lexington, Kentucky, 40536-0093, United States

Location

Montgomery Cancer Center

Mount Sterling, Kentucky, 40353, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109-0936, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Hattiesburg Clinic

Hattiesburg, Mississippi, 39401, United States

Location

Jackson Oncology Associates

Jackson, Mississippi, 39202, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

St. Vincent's Comprehensive Cancer Center

New York, New York, 10011, United States

Location

Summa Health System

Akron, Ohio, 44304, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Dayton Clinical Oncology Program

Dayton, Ohio, 45429, United States

Location

Signal Point Clinical Research Center, LLC

Middletown, Ohio, 45042, United States

Location

Harrington Cancer Center

Amarillo, Texas, 79106, United States

Location

Texas Oncology Cancer Center

Austin, Texas, 78731, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Calgary

Calgary, Alberta, T2N 4N2, Canada

Location

University of Alberta Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

University of Toronto Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Royal Victoria Hospital

Montreal, Quebec, H3A 1A1, Canada

Location

Related Publications (1)

• Vij R, Wang M, Kaufman JL, Lonial S, Jakubowiak AJ, Stewart AK, Kukreti V, Jagannath S, McDonagh KT, Alsina M, Bahlis NJ, Reu FJ, Gabrail NY, Belch A, Matous JV, Lee P, Rosen P, Sebag M, Vesole DH, Kunkel LA, Wear SM, Wong AF, Orlowski RZ, Siegel DS. An open-label, single-arm, phase 2 (PX-171-004) study of single-agent carfilzomib in bortezomib-naive patients with relapsed and/or refractory multiple myeloma. Blood. 2012 Jun 14;119(24):5661-70. doi: 10.1182/blood-2012-03-414359. Epub 2012 May 3.

  PMID: 22555973 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib; WW Domain-Containing Oxidoreductase

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

Intervention Hierarchy (Ancestors)

Short Chain Dehydrogenase-Reductases; NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases; Alcohol Oxidoreductases; Oxidoreductases; Enzymes; Enzymes and Coenzymes; Tumor Suppressor Proteins; Neoplasm Proteins; Proteins; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Onyx Medical Information
• Organization: Onyx Pharmaceuticals, Inc.

medinfo@onyx.com

1-877-ONYX-121

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: September 14, 2007
• First Posted: September 18, 2007
• Study Start: September 1, 2007
• Primary Completion: January 1, 2013
• Study Completion: July 1, 2013
• Last Updated: May 2, 2017
• Results First Posted: December 3, 2015

Record last verified: 2017-04

Locations

CA (4); US (26)