Phase 2 Study of Carfilzomib in Relapsed Multiple Myeloma

NCT ID: NCT00530816

Last Updated: 2017-05-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 164 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-09-30
• Study Completion Date: 2013-07-31

Brief Summary

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

Detailed Description

Two groups of patients with multiple myeloma were initially studied: bortezomib-naïve and bortezomib-treated. Following Amendment 2, only bortezomib-naïve patients were enrolled. Study results were reported in 2 parts, depending on whether a patient received prior bortezomib.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Carfilzomib

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.

Group Type: EXPERIMENTAL

carfilzomib

Intervention Type: DRUG

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

Interventions

carfilzomib

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

Intervention Type: DRUG

Other Intervention Names

PR-171; PR171; Kyprolis® (carfilzomib) for Injection

Eligibility Criteria

Inclusion Criteria

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
• Subjects should be platelet transfusion independent
• Screening absolute neutrophil count (ANC) should be independent of granulocyte colony stimulating factor (G-CSF) or granulocyte macrophage colony stimulating factor (GM-CSF) support for ≥ 1 week and of pegylated G-CSF for ≥ 2 weeks
• Subjects may receive red blood cell (RBC) transfusion or receive supportive care such as erythropoietin and darbepoetin in accordance with institutional guidelines
• Calculated or measured creatinine clearance of ≥ 30 mL/minute, calculated using the formula of Cockcroft and Gault [(140 - Age) X Mass (kg) / (72 X Creatinine mg/dL)]. Multiply result by 0.85 if female.
• Serum creatinine ≤ 2 mg/dL

Ethical / Other

• Written informed consent in accordance with federal, local, and institutional guidelines
• Female subjects of child-bearing potential must have a negative serum pregnancy test within seven days of the first dose and agree to use dual methods of contraception during and for 3 months following last dose of drug. Post menopausal females (> 45 years old and without menses for > 1 year) and surgically sterilized females are exempt from a pregnancy test. Male subjects must use an effective barrier method of contraception during study and for 3 months following the last dose if sexually active with a female of child-bearing potential.
• Subjects must be able to receive outpatient treatment and laboratory monitoring at the institute that administers agent.

Exclusion Criteria

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
• Congestive heart failure (New York Heart Association class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction in the previous six months
• Acute active infection requiring systemic antibiotics, antivirals or antifungals within 2 weeks prior to first dose
• Known or suspected human immunodeficiency (HIV) infection or subjects who are HIV seropositive
• Active hepatitis A, B, or C infection
• Non-hematologic malignancy within the past three 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 6 with stable prostate-specific antigen (PSA)
• Subjects with treatment related myelodysplastic syndrome
• Significant neuropathy (Grade 3, 4 or Grade 2 with pain) at the time of study initiation
• Subjects with known contraindication to receiving allopurinol
• Subjects in whom the required program of oral and intravenous fluid hydration is contraindicated, e.g., due to pre-existing pulmonary, cardiac, or renal impairment
• Subjects with known or suspected amyloidosis Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis
• Any clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent

Ethical / Other

• Female subjects who are pregnant or lactating
• Serious psychiatric or medical conditions that could interfere with treatment

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

Mayo Clinic Scottsdale

Scottsdale, Arizona, United States

Tower Cancer Research Foundation

Beverly Hills, California, United States

Therapeutic Research Institute of Orange County

Laguna Hills, California, United States

Rocky Mountain Blood and Marrow Transplant Program

Denver, Colorado, United States

Oncology & Hematology Assoc. of W. Broward

Tamarac, Florida, United States

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, United States

Emory University Winship Cancer Institute

Atlanta, Georgia, United States

Northwestern University

Chicago, Illinois, United States

Orchard Research

Skokie, Illinois, United States

University of Kentucky College of Medicine

Lexington, Kentucky, United States

Montgomery Cancer Center

Mount Sterling, Kentucky, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Mayo Clinic Rochester

Rochester, Minnesota, United States

Hattiesburg Clinic

Hattiesburg, Mississippi, United States

Jackson Oncology Associates

Jackson, Mississippi, United States

Washington University School of Medicine

St Louis, Missouri, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

St. Vincent's Comprehensive Cancer Center

New York, New York, United States

Summa Health System

Akron, Ohio, United States

Gabrail Cancer Center

Canton, Ohio, United States

Cleveland Clinic

Cleveland, Ohio, United States

Dayton Clinical Oncology Program

Dayton, Ohio, United States

Signal Point Clinical Research Center, LLC

Middletown, Ohio, United States

Harrington Cancer Center

Amarillo, Texas, United States

Texas Oncology Cancer Center

Austin, Texas, United States

MD Anderson Cancer Center

Houston, Texas, United States

University of Calgary

Calgary, Alberta, Canada

University of Alberta Cross Cancer Institute

Edmonton, Alberta, Canada

University of Toronto Princess Margaret Hospital

Toronto, Ontario, Canada

Royal Victoria Hospital

Montreal, Quebec, Canada

Countries

United States; Canada

References

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.

Reference Type: DERIVED

PMID: 22555973 (View on PubMed)

Other Identifiers

PX-171-004

Identifier Type: -

Identifier Source: org_study_id