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    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).

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    Summary
    EudraCT Number:2009-016952-36
    Sponsor's Protocol Code Number:CR0708-12
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2010-07-29
    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 ConcernedUK - MHRA
    A.2EudraCT number2009-016952-36
    A.3Full title of the trial
    A Cancer Research UK Phase I trial of AT9283 (a selective inhibitor of aurora kinases) given over 72 hrs every 21 days via intravenous infusion in children and adolescents aged 6 months to 18 years with relapsed and refractory acute leukaemia.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    AT9283 in children and adolescents with acute leukaemia
    A.3.2Name or abbreviated title of the trial where available
    Phase I study of AT9283 in paediatric acute leukaemia.
    A.4.1Sponsor's protocol code numberCR0708-12
    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 SponsorCancer Research UK
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAstex Therapeutics Ltd
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCancer Research UK
    B.5.2Functional name of contact pointDrug Development Office
    B.5.3 Address:
    B.5.3.1Street AddressAngel Building, 407 St John Street
    B.5.3.2Town/ cityLondon
    B.5.3.3Post codeEC1V 4AD
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+4402072420200
    B.5.5Fax number+4402030147633
    B.5.6E-mailregquery@cancer.org.uk
    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 No
    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 nameAT9283 (as the free base of the L-lactate salt)
    D.3.2Product code AT9283 (as the free base of the L-lactate salt)
    D.3.4Pharmaceutical form Powder for solution for infusion
    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.3.9.2Current sponsor codeAT9283 (as the free base of the L-lactate salt)
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number52
    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 and refractory acute leukaemia
    E.1.1.1Medical condition in easily understood language
    Acute leukaemia
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level PT
    E.1.2Classification code 10000830
    E.1.2Term Acute leukaemia
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    1) To recommend a dose of AT9283 for Phase II evaluation in paediatric patients with acute leukaemia
    E.2.2Secondary objectives of the trial
    1) To evaluate the safety and tolerability of AT9283 given by intravenous (IV) infusion in paediatric patients with acute leukaemia

    2) To document possible evidence of efficacy of AT9283 in paediatric patients with acute leukaemia

    3) To investigate the pharmacokinetic (PK) profile of AT9283 in plasma in paediatric patients with acute leukaemia
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Morphologically proven acute leukaemia

    For acute lymphoblastic leukaemia (ALL), patients must be in second relapse or refractory to induction therapy for first relapse or be in third or subsequent relapse.

    For acute myeloid leukaemia (AML), patients must be in second or subsequent relapse or refractory to an induction therpay for first relapse or otherwise without a curative treatment option.

    For any other type of acute leukaemia, patients must be in first or subsequent relapse or refractory to induction therapy and must not be eligible for any therapy of higher curative potential.

    Patients with Chronic Myeloid Leukaemia (CML) are not eligible.

    For all groups, patients in relapse must have greater than or equal 5% blasts in the bone marrow. Patients with refractory disease following induction must have greater than or equal to 20% blasts in the bone marrow and no evidence of CNS disease.

    2. Life expectancy of at least 8 weeks
    3. Karnofsky / Lansky Play scale ≥50%
    4. Biochemical indices within the ranges shown below. These measurements must be performed within one week (Day -7 to Day -1) before the patient starts treatment.

    Laboratory Test Value required
    Serum bilirubin < 1.5 x upper limit of normal (ULN)

    Alanine aminotransferase (ALT)
    or aspartate aminotransferase (AST) < 2.5 x (ULN) unless raised (or believed to be raised) due to leukaemic infiltration of the liver in which case up to 5 x ULN is permissible

    Calculated creatinine clearance ≥ 60mL/min/1.73m2 (using Schwartz formula)

    5. Aged >6 months to <19 years.

    6.Written (signed and dated) informed consent* and be capable of co-operating with treatment and follow-up

    *Informed consent from the patient’s parent or guardian is required for all patients under 16 years of age. Patients under 16 years of age may also provide written assent to take part in the study.
    E.4Principal exclusion criteria
    1. CML
    2. Cytotoxics, vincristine, anti-neoblastics within two weeks. One week for investigational medicinal products (except antibodies, for which a four week window must be observed); one week for protein kinase inhibitors and Intrathecal therapy before treatment.

    Any patient with ALL experiencing a rapid rise in blast count prior to starting study drug may have oral dexamethasone (6mg/m2/day) for a maximum of five days duration. AT9283 administration may be commenced once steroids have started, however steroids may NOT be started once AT9283 has started.

    Hydroxycarbamide 10-20mg/kg/day (or according to local practice) may be given for two days preceding the start of treatment with AT9283 in patients with AML and hyperleucocytosis.
    3. No evidence of CNS disease
    4. Prior exposure to an aurora kinase inhibitor.
    5. Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or certain Grade 1 toxicities, which in the opinion of the Investigator and the DDO should not exclude the patient.
    6. Pregnant or lactating women are excluded. Female patients with the ability to become pregnant who have a negative serum or urine pregnancy test before enrolment and agree to use two of the following three highly effective forms of combined contraception (oral, injected or implanted hormonal contraception and condom, have a intra-uterine device and condom, diaphragm with spermicidal gel and condom) from the time of consent, during the trial and for six months afterwards are considered eligible.
    7. Male patients with partners of child-bearing potential (unless they agree to take measures not to father children by using one form of highly effective contraception [condom plus spermicide] during the trial and for six months afterwards). Men with pregnant or lactating partners should be advised to use barrier method contraception (for example, condom plus spermicidal gel) to prevent exposure to the foetus or neonate.
    8. Major thoracic or abdominal surgery from which the patient has not yet recovered.
    9. At high medical risk because of non-malignant systemic disease including active uncontrolled infection. Current unstable or uncompensated respiratory or cardiac condition that makes it undesirable for the patient to participate.
    10. Known to be serologically positive for Hepatitis B, Hepatitis C or Human Immunodeficiency Virus (HIV).
    11. Fractional shortening of ≤29% on Echocardiogram
    12. Previous anthracycline treatment with a cumulative dose equal to or greater than 450mg/m2 doxorubicin equivalent
    13. Uncontrolled arterial hypertension, defined as a systolic and / or diastolic blood pressure greater than or equal to the 95th percentile for age and height according to the graphs in Figure 2 of the protocol.
    14. Congenital heart disease, with the exception of patent foramen ovale or small muscular ventricular septal deficit (within the first year of life).
    15. Active graft vs host disease
    16. Patients experiencing significant toxicity following haematopoietic Stem Cell Transplant (HSCT)
    17. Any other condition which in the Investigator’s opinion would not make the patient a good candidate for the clinical trial.
    18. Is a participant or plans to participate in another interventional clinical study, whilst taking part in this Phase I study of AT9283. Participation in an observational study would be acceptable.

    E.5 End points
    E.5.1Primary end point(s)
    Identify a dose level for Phase II exploration
    E.5.1.1Timepoint(s) of evaluation of this end point
    3 years
    E.5.2Secondary end point(s)
    1) Determining causality of adverse events to AT9283 and grading severity according to NCI CTCAE Version 4.02

    2) Identifying Partial remission, Complete remission or Complete remission with incomplete bone marrow recovery using disease specific criteria based upon absolute neutrophil count (ANC), platelets and % blasts in the bone marrow.

    3) Measurement of plasma concentrations of AT9283 in paediatric patients with acute leukaemia
    E.5.2.1Timepoint(s) of evaluation of this end point
    3 years
    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 No
    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) 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
    Paediatric
    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 No
    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.8.3 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 concerned5
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.7Trial has a data monitoring committee No
    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 ‘end of trial’ is defined as the date when the last patient has completed the off-study visit or the final follow-up visit (whichever is the later).
    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 years0
    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: 15
    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) Yes
    F.1.1.4.1Number of subjects for this age range: 5
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 5
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 5
    F.1.2Adults (18-64 years) Yes
    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
    Patients under 16 years of age-will obtain assent where possible
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state18
    F.4.2 For a multinational trial
    F.4.2.2In the whole clinical trial 18
    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 standard 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 Decision2010-08-24
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2010-11-08
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2014-07-01
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