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Multiple MyelomaPhase 2NCT00511238

Phase 2 Study of Carfilzomib in Relapsed and Refractory Multiple Myeloma

A Phase 2 study testing carfilzomib in people with Multiple Myeloma, run by Amgen at 34 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 overall response rate and safety and tolerability of carfilzomib in subjects with relapsed and refractory multiple myeloma. Patients must have received prior treatment with bortezomib and either thalidomide or lenalidomide and be refractory to their last treatment. 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
312 participants
Where
34 sitesin 2 countries
Study dates
Aug 2007to Oct 2012
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 of the following:
  • Serum M-protein ≥ 1 g/dL
  • Urine M-protein ≥ 200 mg/24 hours
  • Serum FLC ≥ 10 mg/dL with abnormal ratio (A0 Only)
Show all 29Show fewer
  • Quantitative immunoglobulin levels using nephelometry or turbidometry (only if protein electrophoresis was felt to be unreliable for M-protein measurement) (A0 Only)
  • Subjects must have been responsive (i.e., achieved an MR or better) to first-line, standard of care therapy
  • Refractory to the most recently received therapy. Refractory disease is defined as ≤ 25% response or progression during therapy or within 60 days after completion of therapy.
  • Subjects must have received ≥ 2 prior regimens for relapsed disease. Induction therapy and stem cell transplant will be considered as one regimen (A1 Only)
  • Subjects must have received prior treatment with bortezomib, and either thalidomide or lenalidomide
  • Subjects must have received an alkylating agent either alone or in combination with other myeloma treatments (history of stem cell transplant is acceptable) (A1 Only)
  • Subjects must have received an anthracycline either alone or in combination with other myeloma treatments, unless not clinically indicated (A1 Only)
  • 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 less than 2.0 times the upper limit of normal, and AST and ALT of less than 3.0 times the upper limit of normal
  • Uric acid within normal range (A0 Only)
  • Total white blood cell (WBC) count ≥ 2.0 × 109/L, absolute neutrophil count (ANC) ≥ 1.0 × 109/L, hemoglobin ≥ 8.0 g/dL, and platelet count ≥ 50.0 × 109/L (A0 Only)
  • Absolute neutrophil count > 1,000/mm3, hemoglobin > 8.0 g/dL, and platelet count > 50,000/mm3 (A1 Only)
  • Subjects should be platelet transfusion independent
  • Screening ANC should be independent of G-CSF or GM-CSF support for ≥ 1 week and of pegylated G-CSF for ≥ 2 weeks
  • Subjects may receive red blood cell (RBC) or platelet transfusions or receive supportive care such as erythropoietin and darbepoetin in accordance with institutional guidelines
  • Calculated and 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.
  • 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.

Who cannot join

  • Disease Related
  • Multiple Myeloma IgM (A1 Only)
  • Subjects who failed to achieve at least a confirmed MR(≥ 25% reduction in M-protein for ≥ 6 weeks) (A1 Only)
  • Subjects with non-secretory multiple myeloma, defined as < 1 g/dL M-protein in serum and < 200 mg/24 hr M-protein in urine
  • Subjects with disease measurable only by serum free light chain (SFLC) analysis (A1 Only)
  • Glucocorticoid therapy (prednisone > 10 mg/day orally or equivalent) within the last three weeks
Show all 28Show fewer
  • 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 Day 1, 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 cardiac ischemia, cardiomyopathy, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction in the previous six months, LVEF < 40
  • Acute active infection requiring systemic antibiotics, antivirals or antifungals within 2 weeks prior to first dose
  • Known or suspected 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 PSA
  • Subjects with treatment related myelodysplastic syndrome
  • Significant neuropathy (Grade 3, 4 or Grade 2 with pain) at the time of study initiation
  • 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 (A1 Only)
  • Subjects with known or suspected amyloidosis (A1 Only)
  • Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis (A1 Only)
  • 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 (A1 Only)
  • Ethical / Other
  • Female subjects who are pregnant or lactating
  • Serious psychiatric or medical conditions that could interfere with treatment

Trial locations and contacts

34 sites in 2 countries.

34 sites in 2 countries

United States28 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Emory University Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Tower Cancer Research Foundation

    Beverly Hills, California, 90211

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Gabrail Cancer Center

    Canton, Ohio, 44718

  • Northwestern Universtiy

    Chicago, Illinois, 60605

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • Oncology & Hematology Care

    Cincinnati, Ohio, 45236

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • City of Hope National Medical Center

    Duarte, California, 91010

  • Florida Cancer Specialists

    Fort Myers, Florida, 33905

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Northwest Cancer Center

    Houston, Texas, 77090

  • Scripps Clinic

    La Jolla, California, 92037

  • University of Kentucky

    Lexington, Kentucky, 40536

  • Southern Cancer Center

    Mobile, Alabama, 36608

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • St. Vincent Catholic Medical Center

    New York, New York, 10011

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Mayo Clinic - Rochester

    Rochester, Minnesota, 55905

  • University of Utah

    Salt Lake City, Utah, 84132

  • University of California, San Francisco

    San Francisco, California, 94143

  • Mayo Clinic Scottsdale

    Scottsdale, Arizona, 85259

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • H. Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

  • Wake Forest University

    Winston-Salem, North Carolina, 27157

Other trials in United States

Canada6 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

  • Jewish General Hospital

    Montreal, Quebec, H3T 1E2

  • Princess Margaret Hospital

    Toronto, Ontario, M5G 2C1

  • Leukemia/BMT Program of BC

    Vancouver, British Columbia, V5Z 1M9

Other trials in Canada

About this study

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

To evaluate the overall response rate and safety and tolerability of carfilzomib in subjects with relapsed and refractory multiple myeloma.

Patients must have received prior treatment with bortezomib and either thalidomide or lenalidomide and be refractory to their last treatment.

Being tested
carfilzomib
Keywords
Onyx, PR171, carfilzomib, multiple myeloma, relapsed, refractory
Medical subject headings
Multiple Myeloma, Recurrence

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

    Subjects will receive carfilzomib 20 mg/m2 as an intravenous bolus over 2 minutes on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles. A maximum of 12 cycles will be administered.

  • carfilzomibDrug

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

    Subjects will receive carfilzomib intravenously over up to 10 minutes on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles. In cycle 1, the dose is 20 mg/m2. If all doses are administered and well-tolerated over Cycle 1, beginning with Cycle 2 the dose will escalate to 27 mg/m2 cycle. A maximum of 12 cycles will be administered.

Study groups in NCT00511238
Study groupRoleWhat they receive
carfilzomib (A0)ExperimentalNot described
Receives: Drug: carfilzomib
carfilzomib (A1)ExperimentalNot described
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)

    For both A0 and A1, to evaluate the best overall response rate (stringent complete response [sCR]+ complete response [CR]+ very good partial response [VGPR]+ partial response [PR]) in patients with multiple myeloma who had previously received bortezomib and either thalidomide or lenalidomide, had relapsed after two or more therapies, and were refractory to the most recently received therapy

    Measured: A0: Subjects evaluated for disease response on Day 24 of Cycles 2, 4, 6, 9, and 12. Onset of response measured on Day 15 of Cycle 1. A1: Subjects evaluated for disease response on Day 15 of Cycle 1, Day 1 of Cycles 2 through 12 and at End of Study.

Secondary outcomes (9)

  1. Clinical Benefit Response (CBR) (A0 Only)

    sCR, CR, VGPR, PR, and minimal response (MR)

    Measured: Response assessments same as described in primary outcome measure

  2. Clinical Benefit Response (CBR) (A1 Only)

    sCR, CR, VGPR, PR, and minimal response (MR)

    Measured: Response assessments same as described in primary outcome measure

  3. Duration of Response (A0 Only)

    Duration of response (DOR) was calculated separately for subjects with clinical benefit response or overall response. DOR is defined as the time from first evidence of PR or better (for overall response) and MR or better (for clinical benefit response) to start of disease progression or death.

    Measured: Response assessments same as described in primary outcome measure

  4. Duration of Response (A1 Only)

    Duration of response (DOR) was calculated separately for subjects with clinical benefit response or overall response. DOR is defined as the time from first evidence of PR or better (for overall response) and MR or better (for clinical benefit response) to start of disease progression or death.

    Measured: Response assessments same as described in primary outcome measure

  5. Time to Progression (A0 Only)

    Time to progression (TTP) is defined as the time from the study entry (first dose of carfilzomib) to disease progression.

    Measured: Response assessments same as described in primary outcome measure

  6. Time to Progression (A1 Only)

    Time to progression (TTP) is defined as the time from the study entry (first dose of carfilzomib) to disease progression.

    Measured: Response assessments same as described in primary outcome measure

  7. Progression-free Survival (A0 Only)

    The PFS was defined as the time from the start of treatment to progressive disease (PD) determined by PI or until death.

    Measured: Response assessments same as described in primary outcome measure

  8. Progression-free Survival (A1 Only)

    The PFS was defined as the time from the start of treatment to progressive disease (PD) determined by PI or until death.

    Measured: Response assessments same as described in primary outcome measure

  9. Overall Survival (A1 Only)

    The time from start of treatment to death due to any cause OS was to be censored on the date the subject was last known to be alive for those who were alive or lost to follow-up as of a data analysis cutoff date.

    Measured: Patients were to be followed by telephone contact for disease progression and OS every 3 months after study discontinuation for the first year and every 6 months thereafter for up to 2 years

Timeline

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

  1. First posted3 Aug 2007 (estimated)
  2. Study startAug 2007
  3. Primary completionNov 2010
  4. Study completionOct 2012

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
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
312 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00511238
Sponsor's protocol ID
PX-171-003
Status last verified
Aug 2017
First submitted
1 Aug 2007
Last updated
31 Aug 2017
Data monitoring committee
No

Publications

  • Siegel DS, Martin T, Wang M, Vij R, Jakubowiak AJ, Lonial S, Trudel S, Kukreti V, Bahlis N, Alsina M, Chanan-Khan A, Buadi F, Reu FJ, Somlo G, Zonder J, Song K, Stewart AK, Stadtmauer E, Kunkel L, Wear S, Wong AF, Orlowski RZ, Jagannath S. A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma. Blood. 2012 Oct 4;120(14):2817-25. doi: 10.1182/blood-2012-05-425934. Epub 2012 Jul 25.

    PubMed 22833546

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 34 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 29 inclusion and 28 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 31 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 34 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 9 Dec 2013). 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) (time frame: A0: Subjects evaluated for disease response on Day 24 of Cycles 2, 4, 6, 9, and 12. Onset of response measured on Day 15 of Cycle 1. A1: Subjects evaluated for disease response on Day 15 of Cycle 1, Day 1 of Cycles 2 through 12 and at End of Study.). 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 NCT00511238, 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 31 Aug 2017.

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