AzTrials
AzTrials

Multiple MyelomaPhase 2NCT00530816

Phase 2 Study of Carfilzomib in Relapsed Multiple Myeloma

A Phase 2 study testing carfilzomib in people with Multiple Myeloma, run by Amgen at 30 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
carfilzomib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
164 participants
Where
30 sitesin 2 countries
Study dates
Sep 2007to Jul 2013
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 24Show fewer
  • 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.

Who cannot join

  • 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
Show all 29Show fewer
  • 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

Trial locations and contacts

30 sites in 2 countries.

30 sites in 2 countries

United States26 sites

  • Summa Health System

    Akron, Ohio, 44304

  • Harrington Cancer Center

    Amarillo, Texas, 79106

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109-0936

  • Emory University Winship Cancer Institute

    Atlanta, Georgia, 404-778-5747

  • Texas Oncology Cancer Center

    Austin, Texas, 78731

  • Tower Cancer Research Foundation

    Beverly Hills, California, 90211

  • Gabrail Cancer Center

    Canton, Ohio, 44718

  • Northwestern University

    Chicago, Illinois, 60605

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Dayton Clinical Oncology Program

    Dayton, Ohio, 45429

  • Rocky Mountain Blood and Marrow Transplant Program

    Denver, Colorado, 80218

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Hattiesburg Clinic

    Hattiesburg, Mississippi, 39401

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Jackson Oncology Associates

    Jackson, Mississippi, 39202

  • Therapeutic Research Institute of Orange County

    Laguna Hills, California, 92653

  • University of Kentucky College of Medicine

    Lexington, Kentucky, 40536-0093

  • Signal Point Clinical Research Center, LLC

    Middletown, Ohio, 45042

  • Montgomery Cancer Center

    Mount Sterling, Kentucky, 40353

  • St. Vincent's Comprehensive Cancer Center

    New York, New York, 10011

  • Mayo Clinic Rochester

    Rochester, Minnesota, 55905

  • Mayo Clinic Scottsdale

    Scottsdale, Arizona, 85259

  • Orchard Research

    Skokie, Illinois, 60076

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Oncology & Hematology Assoc. of W. Broward

    Tamarac, Florida, 33321

  • H. Lee Moffitt Cancer Center & Research Institute

    Tampa, Florida, 33612

Other trials in United States

Canada4 sites

  • University of Calgary

    Calgary, Alberta, T2N 4N2

  • University of Alberta Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

  • Royal Victoria Hospital

    Montreal, Quebec, H3A 1A1

  • University of Toronto Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: An Open-label, Single-arm, Phase 2 Study of Carfilzomib in Patients With Relapsed or Refractory Multiple Myeloma

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

Read the 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.

Being tested
carfilzomib
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • carfilzomibDrug

    Also called PR-171, PR171, Kyprolis® (carfilzomib) for Injection

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

Study groups in NCT00530816
Study groupRoleWhat they receive
CarfilzomibExperimentalParticipants 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.
Receives: Drug: carfilzomib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

  1. Best Overall Response Rate (ORR) in the Response Evaluable 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.

    Measured: 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.

  2. Clinical Benefit Rate (CBR)

    Clinical Benefit Rate is defined as the percentage of participants with a best overall response of minimal response (MR) or better, i.e., a best overall response of sCR, CR, VGPR, PR, or MR. MR was defined as outlined by European Group for Blood and Marrow Transplantation (EBMT) criteria, defined as reduction of M-protein in serum of 25% to 49% and in urine of 50% to 89%, maintained for 6 weeks.

    Measured: 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.

  3. Duration of Response (DOR)

    DOR is defined as the time from first evidence of PR or better to disease progression assessed by the IRC or death due to any cause. Patients lost to follow-up prior to disease progression or who were alive without disease progression before the analysis cutoff date were censored at the last disease assessment.

    Progressive disease was defined as any of the following:

    • An increase of M-protein in serum (absolute increase ≥ 0.5 g/dL) or urine (absolute increase ≥ 200 mg/24 hours) of > 25% from the nadir (if not zero).
    • Percentage of plasma cells in bone marrow ≥ 10%.
    • New or increased size of bone lesions or new plasmacytomas.
    • Patients without measurable serum and urine M-protein: 25% increase from nadir in the difference between involved and uninvolved FLC levels and absolute increase >10 mg/dL.
    • Development of hypercalcemia (corrected serum calcium > 11.5 mg/dL) attributed solely to the proliferative disorder.

    Median DOR was estimated using Kaplan-Meier methods.

    Measured: 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.

  4. Time to Progression (TTP)

    Time to Progression is defined as the time from the start of treatment to IRC-determined disease progression. Patients who were lost to follow-up prior to documentation of disease progression, or who died before documentation of disease progression or who were alive and did not have documentation of disease progression before the data analysis cut-off date were censored at the last disease assessment.

    Median TTP was estimated using the Kaplan-Meier method.

    Measured: 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.

  5. Progression-free Survival (PFS)

    Progression-free Survival (PFS) is defined as the time from start of treatment to IRC determined disease progression or death due to any cause. Patients who were lost to follow-up prior to documentation of disease progression and patients who were alive without disease progression before a data analysis cut-off date were censored at the last disease assessment.

    Median PFS was estimated using the Kaplan-Meier method.

    Measured: 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.

  6. Overall Survival (OS)

    Overall Survival is defined as the time from the start of study treatment to date of death due to any cause.

    Patients who were alive or lost to follow-up as of the data analysis cut-off date for the final OS analysis were censored at the date the patient was last known to be alive. Median OS was estimated using the Kaplan-Meier method.

    Measured: Patients were followed for up to 2 years after study discontinuation. The data cutoff for the analysis is 19 November 2012 for Part 1 and 07 January 2013 for Part 2. Median follow-up time was 19.1 months for Part 1 and 35.9 months in Part 2.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Sep 2007 (estimated)
  2. Study startSep 2007
  3. Primary completionJan 2013
  4. Study completionJul 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
164 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00530816
Sponsor's protocol ID
PX-171-004
Status last verified
Apr 2017
First submitted
14 Sep 2007
Last updated
2 May 2017

Publications

  • 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.

    PubMed 22555973

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing carfilzomib in people with Multiple Myeloma, run by Amgen at 30 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 30 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Dec 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Best Overall Response Rate (ORR) in the Response Evaluable Subset Population (time frame: 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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00530816, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 May 2017.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in