Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2014-005325-12
    Sponsor's Protocol Code Number:20140355
    National Competent Authority:Finland - Fimea
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2016-01-19
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedFinland - Fimea
    A.2EudraCT number2014-005325-12
    A.3Full title of the trial
    A Randomized, Open-label, Phase 3 Study in Subjects with Relapsed and Refractory Multiple Myeloma Receiving
    Carfilzomib in Combination with Dexamethasone, Comparing Once-weekly versus Twice-weekly Carfilzomib Dosing
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study comparing carfilzomib (study drug) given in combination with dexamethasone once a week to twice-weekly carfilzomib in combination with dexamethasone, at the same dose, in patients with cancer of plasma cells which has re-occurred after previous successful treatment or did not show any improvement under previous treatment.
    A.3.2Name or abbreviated title of the trial where available
    A.R.R.O.W.
    A.4.1Sponsor's protocol code number20140355
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorOnyx Therapeutics, Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportOnyx Therapeutics, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAmgen (EUROPE) GmbH
    B.5.2Functional name of contact pointIHQ medical Info-Clinical Trials
    B.5.3 Address:
    B.5.3.1Street AddressDammstrasse 23, P.O. Box 1557
    B.5.3.2Town/ cityZUG
    B.5.3.3Post codeCH-6300
    B.5.3.4CountrySwitzerland
    B.5.6E-mailMedinfoInternational@amgen.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Kyprolis
    D.2.1.1.2Name of the Marketing Authorisation holderAmgen Europe B.V
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/08/548
    D.3 Description of the IMP
    D.3.1Product nameCarfilzomib
    D.3.2Product code PR-171
    D.3.4Pharmaceutical form Lyophilisate for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCarfilzomib
    D.3.9.1CAS number 868540-17-4
    D.3.9.2Current sponsor codePR-171
    D.3.9.3Other descriptive nameFP-101; 506160 - CARFILZOMIB
    D.3.9.4EV Substance CodeSUB32911
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number60
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Multiple Myeloma
    E.1.1.1Medical condition in easily understood language
    Cancer of plasma cells, a type of white blood cell normally responsible for producing antibodies
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10028228
    E.1.2Term Multiple myeloma
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To compare the progression-free survival (PFS) of once weekly carfilzomib dosing in combination with dexamethasone to the PFS of twice weekly carfilzomib dosing in combination with dexamethasone in subjects with relapsed and refractory multiple myeloma who have received prior treatment with a proteasome inhibitor and an IMiD
    (immunomodulatory agent).
    E.2.2Secondary objectives of the trial
    - Overall response rate (ORR)
    - Overall survival (OS)
    - Safety and tolerability
    - Pharmacokinetics (PK) of carfilzomib using sparse sampling
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    INTENSIVE PHARMACOKINETICS/PHARMACODYNAMICS SUBSTUDY
    & SPARSE PHARMACOKINETIC SAMPLING
    E.3Principal inclusion criteria
    101. Age ≥ 18 years
    102. Able to provide written informed consent in accordance with federal, local,
    and institutional guidelines
    103. Relapsed multiple myeloma
    104. Refractory multiple myeloma, defined as meeting 1 or more of the following:
    a. Nonresponsive to most recent therapy (stable disease or progressive disease
    [PD] while on treatment), or
    b. Disease progression within 60 days of discontinuation from most recent
    therapy
    105. At least 2, but no more than 3, prior lines of therapy for multiple myeloma
    106. Prior exposure to an IMiD
    107. Prior exposure to a proteasome inhibitor (PI)
    108. Documented response of at least partial response (PR) to at least 1 prior line of
    therapy
    109. Measurable disease, with at least 1 of the following assessed at a central
    laboratory within the 21 days prior to randomization:
    a. Serum M-protein ≥ 0.5 g/dL
    b. Urine M-protein ≥ 200 mg/24 hours
    c. In subjects without measurable serum or urine M-protein, serum free light
    chain (SFLC) ≥ 100 mg/L (involved light chain) and an abnormal serum
    kappa:lambda ratio
    110. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
    111. Left ventricular ejection fraction (LVEF) ≥ 40% within the 21 days prior to
    randomization
    112. Adequate organ and bone marrow function performed at a central laboratory
    within the 21 days prior to randomization, defined by:
    a. Bilirubin < 1.5 times the upper limit of normal (ULN)
    b. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
    < 3 times the ULN
    c. Absolute neutrophil count (ANC) ≥ 1 × 109/L (screening ANC must be
    independent of growth factor support for ≥ 7 days)
    d. Hemoglobin ≥ 8 g/dL (Use of erythropoietic stimulating factors and red blood
    cell [RBC] transfusions per institutional guidelines are allowed, however the
    most recent RBC transfusion may not have been done within 7 days prior to
    obtaining the screening hemoglobin.)
    e. Platelet count ≥ 50,000/mm3 (≥ 30,000/mm3 if myeloma involvement in the
    bone marrow is > 50%. Subjects must not have received platelet transfusions
    for at least 7 days prior to obtaining the screening platelet count.)
    f. Calculated or measured creatinine clearance (CrCl) of ≥ 30 mL/min.
    Calculation must be based on the Cockcroft and Gault formula:
    [(140 – Age) × Mass (kg) / (72 × Creatinine mg/dL)]; multiply result by 0.85
    if female
    113. Females of childbearing potential (FCBP) must have a confirmed negative serum
    pregnancy test performed at a central laboratory, within the 21 days prior to
    randomization, and must not be breastfeeding.
    114. Females of childbearing potential must agree to use highly effective method(s) of
    contraception, during the study and for 30 days following the last study drug
    administration. (Refer to Appendix K for specific contraceptive
    requirements).
    115. Male subjects who are sexually active with an FCBP must agree to use
    condoms (unless they have had a vasectomy with medical confirmation of
    surgical success), during treatment and for an additional 90 days following
    the last study drug administration.
    116. Male subjects must agree to not donate sperm, during treatment and for an
    additional 90 days following the last study drug administration.
    E.4Principal exclusion criteria
    201. Waldenström macroglobulinemia
    202. Multiple myeloma of Immunoglobulin M (IgM) subtype
    203. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal
    protein, and skin changes)
    204. Plasma cell leukemia (> 2.0 × 109/L circulating plasma cells by standard
    differential)
    205. Myelodysplastic syndrome
    206. Second malignancy within the past 5 years except:
    a. Adequately treated basal cell or squamous cell skin cancer
    b. Carcinoma in situ of the cervix
    c. Prostate cancer < Gleason score 6 with stable prostate-specific antigen (PSA)
    over 12 months
    d. Ductal breast carcinoma in situ with full surgical resection (i.e., negative
    margins)
    e. Treated medullary or papillary thyroid cancer
    f. Similar condition with an expectation of > 95% five-year disease-free survival
    207. History of or current amyloidosis
    208. Cytotoxic chemotherapy or other antineoplastic therapy, aside from
    immunotherapy or proteasome inhibitors, within the 28 days prior to
    randomization
    209. Immunotherapy, such as an IMiD, or a proteasome inhibitor, within the
    21 days prior to randomization
    210. Glucocorticoid therapy exceeding a cumulative dose of 160 mg dexamethasone or
    equivalent, within the 14 days prior to randomization
    211. Radiation therapy:
    a. Focal therapy within the 7 days prior to randomization
    b. Extended field therapy within the 21 days prior to randomization
    212. Prior treatment with either carfilzomib or oprozomib
    213. Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize
    carfilzomib)
    214. Contraindication to dexamethasone or any of the required concomitant
    medications or supportive treatments
    215. Active congestive heart failure (New York Heart Association [NYHA] Class III
    or IV, refer to Appendix F), symptomatic ischemia, conduction abnormalities
    uncontrolled by conventional intervention, acute diffuse infiltrative pulmonary
    disease, pericardial disease, or myocardial infarction within 6 months prior to
    randomization
    216. Active infection requiring systemic treatment within the 14 days prior to
    randomization
    217. Pleural effusions requiring thoracentesis within the 14 days prior to randomization
    218. Ascites requiring paracentesis within the 14 days prior to randomization
    219. Ongoing graft-versus-host disease
    220. Uncontrolled hypertension or diabetes mellitus
    221. Significant neuropathy (≥ Grade 3) within the 14 days prior to randomization
    222. Known cirrhosis
    223. Known human immunodeficiency virus (HIV) seropositivity, hepatitis C
    infection, or hepatitis B infection. Subjects with past hepatitis B virus infection,
    defined as having a negative HBsAg test and a positive antibody to hepatitis B
    core antigen (anti-HBc) antibody test, are eligible. Subjects positive for hepatitis
    C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is
    negative for HCV RNA.
    224. Participation in another interventional study within the 28 days prior to
    randomization
    225. Major surgery (except kyphoplasty) within the 28 days prior to randomization
    227. Any other clinically significant medical disease or social condition that, in the
    investigator’s opinion, may interfere with protocol adherence or a subject’s ability
    to give informed consent, be compliant with study procedures, or provide accurate
    information.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is PFS, which is defined as the time in months from randomization to the earlier of disease progression or death due to any cause.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The final PFS analysis will be conducted when approximately 350 PFS events have occurred or by end of year 2018, whichever is earlier. A total of 350 PFS events will provide 83% power to detect a significant difference in PFS between the 2 treatment groups with 1 interim analysis if the underlying HR is 0.73. The interim analysis will be
    performed when approximately 75% of the total PFS events (i.e., 263 events) have occurred.

    E.5.2Secondary end point(s)
    The secondary endpoints of the study are as follows:
    - ORR, defined as the proportion of subjects who achieved a confirmed PR, VGPR, CR, or sCR, according to the IMWG-URC.
    - OS defined as the time in months from randomization to death due to any cause.
    - Safety and tolerability
    - Sparse PK
    E.5.2.1Timepoint(s) of evaluation of this end point
    - ORR will be analyzed at the time of the PFS analysis (interim or final), only if the PFS analysis crosses the boundary.
    - The analysis of OS will be conducted at the time of the PFS analysis (interim or final), only if both PFS and ORR analyses are positive
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA85
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Belgium
    Bulgaria
    Canada
    Czech Republic
    Denmark
    Finland
    France
    Germany
    Greece
    Hungary
    Italy
    Japan
    Norway
    Poland
    Romania
    Spain
    Sweden
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The primary completion date is defined as the date when the last subject is assessed or receives an intervention for the final collection of data for the primary endpoint(s), for the purposes of conducting the primary analysis, whether the study concluded as planned in the protocol or was terminated early.
    The end of study date is defined last subject last visit, following any additional parts in the study (e.g., long-term follow-up), as applicable.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 160
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 300
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state6
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 418
    F.4.2.2In the whole clinical trial 460
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Standard of Care
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2016-02-12
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-03-16
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2019-01-07
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sun May 05 21:34:11 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA