AzTrials
AzTrials

Relapsed Multiple MyelomaPhase 1NCT00603447

Phase 1b Multicenter Study of Carfilzomib With Lenalidomide and Dexamethasone in Relapsed Multiple Myeloma

A Phase 1 study testing Carfilzomib, Lenalidomide and Dexamethasone in people with Relapsed Multiple Myeloma, run by Amgen at 12 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 safety and maximum tolerated dose (MTD) of carfilzomib in combination with lenalidomide and dexamethasone in patients with relapsed multiple myeloma Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Relapsed Multiple Myeloma
What is being tested?
Carfilzomib, Lenalidomide and Dexamethasone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
84 participants
Where
12 sitesin 2 countries
Study dates
May 2008to Jan 2016
Phase
Phase 1
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:
  • Symptomatic multiple myeloma
  • Relapsed or progressive disease after at least one but no more than three prior therapeutic treatments or regimens for multiple myeloma
  • Prior therapeutic treatment regimens may have included bortezomib, lenalidomide, and/or thalidomide, among other agents.
  • If previously treated with lenalidomide or bortezomib, the subject must not have progressed during the first 3 months of treatment with the drug and must not have discontinued treatment due to lenalidomide intolerance (bortezomib intolerant subjects may enroll).
  • Measurable disease, as indicated by one or more of the following:
Show all 30Show fewer
  • Serum M-protein ≥ 0.5 g/dL
  • Urine Bence-Jones protein ≥ 200 mg/24 h
  • If Serum Protein Electrophoresis is felt to be unreliable for routine M-protein measurement (particularly for patients with Immunoglobulin (Ig)A multiple myeloma), then quantitative immunoglobulin levels can be accepted.
  • Prior to enrollment, sites must provide evidence of myeloma progression/relapse, with start and stop dates of the most recent treatment regimen, as well as best tumor response to all prior treatment regimens.
  • Demographic
  • Males and females ≥ 18 years of age
  • Life expectancy of more than three months
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
  • Laboratory
  • Adequate hepatic function, with bilirubin < 2 times the upper limit of normal (ULN) and alanine aminotransferase (ALT) < 3 times ULN
  • Absolute neutrophil count (ANC) ≥ 1,000/mm³, hemoglobin ≥ 8 gm/dL, platelet count ≥ 50,000/ mm³ (≥ 30 × 10^9/L if myeloma involvement in the bone marrow is > 50%)
  • Screening ANC should be independent of granulocyte- and granulocyte/macrophage colony stimulating factor (G-CSF and GM-CSF) support for at least 1 week and of pegylated G-CSF for at least 2 weeks.
  • Subjects may receive red blood cell (RBC) or platelet transfusions, if clinically indicated, in accordance with institutional guidelines
  • Screening platelet count should be independent of platelet transfusions for at least 2 weeks
  • Calculated or measured creatinine clearance of ≥ 50 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). Other generally accepted calculation methods can be substituted.
  • Ethical/Other
  • Written informed consent in accordance with federal, local, and institutional guidelines
  • Females of childbearing potential (FCBP) must agree to ongoing pregnancy testing
  • FCBP* must have a negative serum or urine pregnancy test, with a sensitivity of at least 50 mIU/mL within 10-14 days (US/RevAssist®) or 25 mIU/mL within 7-14 days (Canada/RevAidSM), prior to and again within 24 hours of starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or to use two methods of reliable birth control, including at least one highly effective method AND one additional effective method of birth control (contraception) AT THE SAME TIME, beginning 4 weeks prior to initiating treatment with lenalidomide, during therapy, during therapy delay, and continuing for 4 weeks following discontinuation of lenalidomide therapy. If a hormonal method (birth control pills, injections, patch or implants) or intrauterine device (IUD) is not medically possible for the subject, the subject may use another highly effective method or two barrier methods AT THE SAME TIME.
  • Male subjects must agree to NEVER have unprotected sexual contact with a female who can become pregnant and must agree to either completely abstain from sexual contact with females who are pregnant or are able to become pregnant, or he must use a latex condom EVERY TIME he engages in any sexual contact with females who are pregnant or may become pregnant while he is taking lenalidomide and for 4 weeks after he stops taking the drug, even if he has had a successful vasectomy. The subject must agree to inform his physician if he has had unprotected sexual contact with a female who can become pregnant or if he thinks FOR ANY REASON, that his sexual partner may be pregnant.
  • Male subjects cannot donate semen or sperm while taking lenalidomide.
  • All study participants must be registered into the mandatory RevAssist (US) or RevAid (Canada) programs and be willing and able to comply with the requirements of Rev Assist/RevAid
  • Subjects must adhere to the study visit schedule and other protocol requirements and receive outpatient treatment and laboratory monitoring at the institute that administers the drug
  • Subjects must agree to take enteric-coated aspirin 81-325 mg orally daily, or if history of prior thrombotic disease or allergy to aspirin, must be fully anticoagulated with warfarin (INR 2-3) or be treated with full-dose, low molecular weight heparin, as if to treat deep venous thrombosis (DVT)/pulmonary embolism.

Who cannot join

  • Disease related
  • Subjects with non-secretory or hyposecretory multiple myeloma, defined as < 0.5 g/dL M-protein in serum, < 200 mg/24 hr Bence Jones protein in urine, or disease only measured by serum free light chain (FLC)
  • Subjects who never achieved at least a durable minimal response (MR, ≥ 25% reduction in M-protein for at least 6 weeks) on any prior therapy
  • Corticosteroid therapy in a dose equivalent to dexamethasone ≥ 4 mg/day or prednisone ≥ 20 mg/day within 3 weeks prior to first dose
  • Use of any other experimental drug or therapy within 28 days of baseline
  • POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
Show all 31Show fewer
  • Plasma cell leukemia
  • Waldenström's macroglobulinemia
  • Chemotherapy with approved or investigative anticancer therapeutics, including steroid therapy dose as defined above, within 3 weeks prior to first dose
  • Radiation therapy or immunotherapy within 4 weeks prior to first dose; localized radiation therapy within 1 week prior to first dose
  • Planned radiation therapy that occurs after the start of treatment
  • Participation in an investigational therapeutic study within 3 weeks or within 5 drug half-lives (t1/2) prior to first dose, whichever time is greater.
  • Concurrent conditions
  • Pregnant or lactating females
  • History of allergy to boron or mannitol
  • Major surgery within 3 weeks prior to first dose
  • 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
  • Uncontrolled hypertension
  • Acute active infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose
  • Known or suspected human immunodeficiency virus (HIV) infection, known HIV seropositivity, or active hepatitis A, B, or C infection
  • Non-hematologic malignancy within the past three years except
  • adequately treated basal cell or squamous cell skin cancer,
  • carcinoma in situ of the cervix, or
  • prostate cancer < Gleason Grade 6 with stable prostate specific antigen (PSA) levels
  • Serious psychiatric or medical conditions that could interfere with treatment
  • Significant neuropathy (Grade 3, Grade 4, or Grade 2 with pain) at the time of the first dose and/or within 14 days before enrollment
  • Contraindication to any of the required concomitant drugs, including proton-pump inhibitor (e.g., lansoprazole), enteric-coated aspirin or other anticoagulant, or if a history of prior thrombotic disease, warfarin or low molecular weight heparin
  • 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
  • Prior carfilzomib treatment

Trial locations and contacts

12 sites in 2 countries.

12 sites in 2 countries

United States11 sites

  • Gabrail Cancer Center

    Canton, Ohio, 44718

  • Northwestern University

    Chicago, Illinois, 60611

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Pacific Shores Medical Group

    Long Beach, California, 90813

  • Cedars Sinai Medical Center

    Los Angeles, California, 90048

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Cornell University

    New York, New York, 10021

  • University of California San Francisco

    San Francisco, California, 94143

  • Fred Hutch Cancer Research Center

    Seattle, Washington, 98103-1204

  • H. Lee Moffitt Cancer Center & Research Institute

    Tampa, Florida, 33612

Other trials in United States

Canada1 site

  • Jewish General Hospital

    Montreal, Quebec, H3T 1E2

Other trials in Canada

About this study

Official title: Phase 1b Multicenter Dose Escalation Study of Carfilzomib With Lenalidomide and Dexamethasone for Safety and Activity in Relapsed Multiple Myeloma

To evaluate the safety and maximum tolerated dose (MTD) of carfilzomib in combination with lenalidomide and dexamethasone in patients with relapsed multiple myeloma

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 Kyprolis®

    Carfilzomib for Injection was administered intravenously over 10 minutes on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle for the first 12 cycles. Each dose of Carfilzomib for Injection was normalized to body surface area.

  • LenalidomideDrug

    Also called REVLIMID®

    Lenalidomide was administered orally on Days 1 to 21 of each 28-day cycle.

  • DexamethasoneDrug

    Dexamethasone 40 mg orally or intravenous equivalent was administered 30 minutes to 4 hours before carfilzomib on Days 1, 8, and 15, as well as on Day 22 of each 28-day cycle.

Study groups in NCT00603447
Study groupRoleWhat they receive
Carfilzomib + Lenalidomide + DexamethasoneExperimentalTreatment during Cycles 1 through 12 consisted of carfilzomib (15, 20, or 20/27 mg/m²) on Days 1, 2, 8, 9, 15, and 16; lenalidomide (10, 15, 20, or 25 mg) on Days 1 to 21; and low-dose dexamethasone (40 mg) given 30 minutes to 4 hours before the carfilzomib dose on Days 1, 8, and 15, as well as on Day 22. For Cycles 13 and higher, carfilzomib could be omitted on Days 8 and 9 at the investigator's discretion.
Receives: Drug: Carfilzomib; Drug: Lenalidomide; Drug: Dexamethasone

What is being measured

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

  1. Number of Participants With Adverse Events (AEs)

    Treatment-related are those AEs with possible or probable relationship to carfilzomib, lenalidomide or dexamethasone as assessed by the Investigator. The severity of each adverse event was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0, per the following: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death.

    Serious adverse events were defined as AEs meeting one of the following: death, life-threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect in the offspring of an exposed participant, important medical events that may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed above, or pregnancy or suspected pregnancy.

    Measured: From the first dose of study drug until 30 days after the last dose; 1 to 52 months, with an average of 12 months.

  2. Number of Participants With Dose-limiting Toxicities

    Dose-limiting toxicity was defined as any of the following events assessed as related to carfilzomib, lenalidomide, or dexamethasone: Nonhematologic

    • ≥ Grade 2 neuropathy with pain
    • ≥ Grade 3 nonhematologic toxicity (excluding nausea, vomiting, diarrhea, hyperglycemia due to dexamethasone, and rash due to lenalidomide)
    • ≥ Grade 3 nausea, vomiting, or diarrhea uncontrolled by maximal supportive therapy
    • ≥ Grade 4 fatigue persisting > 7 days
    • Treatment delay for toxicity > 21 days

    Hematologic

    • Grade 4 neutropenia (absolute neutrophil count [ANC] < 500/mm³) > 7 days
    • Febrile neutropenia (ANC < 1,000/mm³ with fever ≥ 38.3ºC)
    • Grade 4 thrombocytopenia (platelets < 25,000/mm³) for > 7 days despite holding treatment, or Grade 3 or 4 thrombocytopenia associated with bleeding
    • Treatment delay for toxicity > 21 days.

    The maximum-tolerated dose was defined as the dose level below which a drug-related DLT was observed in ≥ 33% of participants in a cohort.

    Measured: Cycle 1, 28 days

Timeline

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

  1. First posted29 Jan 2008 (estimated)
  2. Study startMay 2008
  3. Primary completionMay 2013
  4. Study completionJan 2016

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
84 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00603447
Sponsor's protocol ID
PX-171-006
Status last verified
Apr 2017
First submitted
16 Jan 2008
Last updated
30 May 2017
Data monitoring committee
No

Publications

  • Wang M, Martin T, Bensinger W, Alsina M, Siegel DS, Kavalerchik E, Huang M, Orlowski RZ, Niesvizky R. Phase 2 dose-expansion study (PX-171-006) of carfilzomib, lenalidomide, and low-dose dexamethasone in relapsed or progressive multiple myeloma. Blood. 2013 Oct 31;122(18):3122-8. doi: 10.1182/blood-2013-07-511170. Epub 2013 Sep 6.

    PubMed 24014245

  • Niesvizky R, Martin TG 3rd, Bensinger WI, Alsina M, Siegel DS, Kunkel LA, Wong AF, Lee S, Orlowski RZ, Wang M. Phase Ib dose-escalation study (PX-171-006) of carfilzomib, lenalidomide, and low-dose dexamethasone in relapsed or progressive multiple myeloma. Clin Cancer Res. 2013 Apr 15;19(8):2248-56. doi: 10.1158/1078-0432.CCR-12-3352. Epub 2013 Feb 27.

    PubMed 23447001

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Carfilzomib, Lenalidomide and Dexamethasone in people with Relapsed Multiple Myeloma, run by Amgen at 12 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 30 inclusion and 31 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 30 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 12 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 Jun 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?

Number of Participants With Adverse Events (AEs) (time frame: From the first dose of study drug until 30 days after the last dose; 1 to 52 months, with an average of 12 months.). The study lists 2 primary outcomes in all. 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 NCT00603447, which also lists 2 linked publications.

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 30 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