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The European Union Clinical Trials Register allows you to search for protocol and results information on:
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    The EU Clinical Trials Register currently displays   42869   clinical trials with a EudraCT protocol, of which   7063   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 in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

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    Summary
    EudraCT Number:2014-001633-84
    Sponsor's Protocol Code Number:20140106
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2016-02-15
    Trial 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 ConcernedNetherlands - Competent Authority
    A.2EudraCT number2014-001633-84
    A.3Full title of the trial
    Phase 1b Study of Carfilzomib in Combination with Induction Chemotherapy in Children with Relapsed or Refractory Acute Lymphoblastic Leukemia
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Phase 1b Study of Carfilzomib in Combination with Induction Chemotherapy in Children with Relapsed or Refractory Acute Lymphoblastic Leukemia
    A.4.1Sponsor's protocol code number20140106
    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 No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameCarfilzomib Lyophilisate for Solution for Injection
    D.3.2Product code PR-171
    D.3.4Pharmaceutical form Powder 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 nameCARFILZOMIB
    D.3.9.4EV Substance CodeSUB32911
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2
    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
    Relapsed or Refractory Acute Lymphoblastic Leukemia
    E.1.1.1Medical condition in easily understood language
    A group of cancers that usually begins in the bone marrow and results in high numbers of abnormal white blood cells.
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.1
    E.1.2Level LLT
    E.1.2Classification code 10025230
    E.1.2Term Lymphatic leukemia
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    - To assess the safety and tolerability of carfilzomib, alone and in combination with induction chemotherapy, for the treatment of children with relapsed or refractory acute lymphoblastic leukemia (ALL)
    -To determine the maximum tolerated dose (MTD) of carfilzomib in combination with induction chemotherapy.

    E.2.2Secondary objectives of the trial
    -To characterize the pharmacokinetics (PK) of carfilzomib alone and in
    combination with induction chemotherapy
    -To evaluate the combined rate of bone marrow complete response (CR) and bone marrow CR without platelet recovery (CRp) at the end of the Induction Cycle
    -To estimate the proportion of subjects who achieve minimal residual disease (MRD) status < 10-3 and < 10-4 lymphoblasts at the end of the Induction Cycle

    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Age 21 years or younger at the time of initial ALL diagnosis and age > 1 year
    at the time of study treatment initiation.
    2. Subjects must have a diagnosis of ALL with ≥ 5% blasts in the bone marrow
    (M2 or M3 disease), with or without extramedullary disease.
    • To be eligible, subjects must have had 1 or more prior therapeutic attempts,
    defined as:
    o Early first relapse (< 36 months from original diagnosis) after
    achieving a CR (B-ALL) or first relapse any time following the
    original diagnosis after achieving a CR (T-ALL)
    OR
    o Relapse after achieving a CR following the first or subsequent relapse
    (i.e., ≥ 2 relapses)
    OR
    o Failing to achieve a CR from original diagnosis after at least 1 induction attempt
    3. Subjects must have fully recovered from the acute toxic effects of all previous
    chemotherapy, immunotherapy, or radiotherapy treatment before enrollment.
    4. Subjects must have a serum creatinine level that is ≤ 1.5 × institutional upper
    limit of normal (ULN) according to age. If serum creatinine level is
    > 1.5 × ULN, the subject must have a calculated creatinine clearance or
    radioisotope glomerular filtration rate (GFR) ≥ 70 mL/min/1.73 m2.
    5. Adequate liver function, defined as both of the following:
    • Total bilirubin ≤ 1.5 × institutional ULN, except in the presence of Gilbert
    syndrome. For those with hyperbilirubinemia due to Gilbert syndrome, subjects are only eligible if they have a direct bilirubin ≤ 1.5 × institutional ULN.
    • ALT ≤ 5 × institutional ULN
    6. Performance status: Karnofsky or Lansky scores ≥ 50 for subjects > 16 years
    old or ≤ 16 years old, respectively.
    7. Females of childbearing potential (FCBP) must have a negative serum or urine
    pregnancy test within 48 hours prior to study treatment initiation.
    8. Females of childbearing potential and male subjects who are sexually active
    with a FCBP must agree to use a highly effective method of contraception plus a
    male condom during the study and for 6 months following the last dose of study
    treatment. The methods of contraception are defined in the ICF. Where
    required by local laws, regulations, and/or guidelines, additional country specific
    requirements are outlined in a country-specific protocol addendum.
    9. Subjects must provide written informed consent and paediatric assent in
    accordance with federal, local, and institutional laws and regulations.
    E.4Principal exclusion criteria
    Exclusion criteria: Exclusion criteria for the study are the following:
    1. Known allergy to any of the drugs used in the study.
    (Subjects who have had a previous allergy to PEG-asparaginase but can receive
    Erwinia are eligible.)
    2. Known allergy to Captisol (a cyclodextrin derivative used to solubilize
    carfilzomib; for a complete listing of Captisol-enabled drugs, see the Ligand
    Pharmaceuticals, Inc. website)
    3. Left ventricular fractional shortening < 30%
    4. History of ≥ Grade 2 pancreatitis
    5. Active graft-versus-host disease requiring systemic treatment
    6. Positive culture for or other clinical evidence of infection with bacteria or
    fungus within 14 days of the initiation of study treatment
    7. Down Syndrome
    8. Prior therapy restrictions:
    • Subjects must have completed therapy with granulocyte-colony stimulating
    factor (G-CSF) or other myeloid growth factors at least 7 days before study
    treatment initiation, or at least 14 days before study treatment initiation,
    if pegylated myeloid growth factors were administered.
    • Subjects must have received the last dose of a non-monoclonal antibody
    biologic agent at least 7 days before study treatment initiation. For
    agents that have known adverse events (AEs) occurring beyond 7 days after
    the last administration, this period must be extended beyond the time
    during which AEs are known to occur, and the Sponsor study medical
    monitor should be contacted.
    • At least 3 antibody half-lives must have elapsed since the last dose of
    monoclonal antibody (e.g., 66 days for rituximab and 69 days for
    epratuzumab) before subjects may initiate study treatment.
    • Subjects must have completed any type of active immunotherapy
    (e.g., tumor vaccines) at least 42 days before study treatment initiation.
    • Subjects must not have received other antineoplastic agents with therapeutic intent, excluding hydroxyurea and antimetabolites administered as part of maintenance chemotherapy, within 7 days prior to study treatment initiation.
    9. Females who are pregnant and/or breastfeeding
    E.5 End points
    E.5.1Primary end point(s)
    • Safety and tolerability of carfilzomib alone and in combination with induction
    chemotherapy as defined by the type, incidence, severity, and outcome of adverse events (AEs); changes from baseline in key laboratory analytes, vital signs, and physical findings. Time to toxicity will be evaluated to differentiate single-agent carfilzomib from carfilzomib in combination with induction chemotherapy
    • Determination of the MTD as the dose that has the highest posterior probability of having a DLT rate within the target toxicity interval (20%–33%), while the posterior probability of excessive /unacceptable toxicity (>33%–100%) is less than 40%
    E.5.1.1Timepoint(s) of evaluation of this end point
    End of the Induction Cycle
    E.5.2Secondary end point(s)
    •Pharmacokinetic parameters, principally maximum plasma concentration (Cmax) and area under the curve (AUC), alone and in combination with induction
    chemotherapy, derived from levels of carfilzomib assayed in PK samples
    • Combined proportion of subjects who achieve CR or CRp at the end of the
    Induction Cycle
    • Proportion of subjects who achieve MRD status < 10-3 and < 10-4 lymphoblasts at the end of the Induction Cycle as assessed by quantitative immunoglobulin/T-cell receptor (Ig/TcR) polymerase chain reaction (PCR)

    E.5.2.1Timepoint(s) of evaluation of this end point
    End of the Induction Cycle
    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 Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    dose-escalation study
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    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) Information not present in EudraCT
    E.8.2.2Placebo No
    E.8.2.3Other No
    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 concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA26
    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
    Australia
    Austria
    Belgium
    Canada
    Denmark
    France
    Germany
    Israel
    Netherlands
    Spain
    Switzerland
    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
    End of study per protocol is defined as, the end of study assessments must be completed 30 days (± 4 days) following the last dose of study treatment.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    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 years3
    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 Yes
    F.1.1Number of subjects for this age range: 26
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) Yes
    F.1.1.4.1Number of subjects for this age range: 12
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 2
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 12
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) No
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Subjects are under 18 years old.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state2
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 17
    F.4.2.2In the whole clinical trial 48
    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)
    As per protocol
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation ITCC Gustave Roussy ENCCA
    G.4.3.4Network Country France
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2016-02-15
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-07-27
    P. End of Trial
    P.End of Trial StatusOngoing
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