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    The EU Clinical Trials Register currently displays   43845   clinical trials with a EudraCT protocol, of which   7282   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:2004-001853-27
    Sponsor's Protocol Code Number:BIOV-111
    National Competent Authority:Austria - BASG
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2005-09-14
    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 ConcernedAustria - BASG
    A.2EudraCT number2004-001853-27
    A.3Full title of the trial
    A Phase II, Open-Label Study of Clofarabine in Paediatric Patients with Refractory / Relapsed Acute Lymphoblastic Leukaemia
    A.3.2Name or abbreviated title of the trial where available
    BIOV-111
    A.4.1Sponsor's protocol code numberBIOV-111
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorBioenvision Limited
    B.1.3.4CountryUnited Kingdom
    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 support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    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 Information not present in EudraCT
    D.2.1.1.1Trade name CLOLAR
    D.2.1.1.2Name of the Marketing Authorisation holderGenzyme Corporation
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    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/3/01/082
    D.3 Description of the IMP
    D.3.1Product nameClofarabine
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    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 INNClofarabine
    D.3.9.3Other descriptive name2-chloro-9-(2.-deoxy-2.-fluoro-ß-D-arabinofuranosyl)-9H-purine-6-amine
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1 to kg
    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) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.8Extractive medicinal product Information not present in EudraCT
    D.3.11.9Recombinant medicinal product Information not present in EudraCT
    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 leukaemia (ALL) in children
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 8.0
    E.1.2Level Lowe
    E.1.2Classification code 10050281
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To determine the overall response (OR) rate in paediatric patients with refractory or relapsed ALL. The OR rate is defined as the sum of the number of patients with either complete response (CR) or complete response in the absence of total platelet recovery (CRp) divided by the toal number of patients evaluable for response.
    E.2.2Secondary objectives of the trial
    1. To document the rate of CR(s) in the study population.
    2. To document the rate of CRp(s) in the study population.
    3. To document the rate of partial response (PR(s)) in the study population.
    4. To document the modified overall response (MOR) rate in paediatric patients with refractory or relapsed ALL.
    5. To document time-to-event parameters including duration of remission and overall survival (OS).
    6. To document the safety profile and tolerability of clofarabine for this population and dosing regimen.
    7. To document the number of patients receiving bone marrow transplantation or peripheral blood stem cell transplantation and the time to transplant following commencement of Clofarabine.
    8. To determine the pharmacokinetic profile and intracellular triphosphate levels of Clofarabine in selected patients.
    9. To document the metabolic pathways that may predict Clofarabine sensitivity or resistance.
    E.2.3Trial contains a sub-study Information not present in EudraCT
    E.3Principal inclusion criteria
    The trial will recruit patients who have failed to achieve response by standard first line therapy or following first relapse, fail to achieve response by standard relapse therapy. Children who have received an allogeneic progenitor cell transplant, must be at least 6-months post transplant. For Inclusion/Exclusion criteria, a ‘prior regimen’ is defined as including one or more of the following: Induction, Consolidation and Maintenance therapies. Patients must meet all of the following criteria for admission in the study.

    1. Have a diagnosis of ALL
    2. Be ≤21 years old at time of initial diagnosis.
    3. i. Patients with primary, refractory ALL must have an M3 marrow at the end of conventional induction chemotherapy or have an M2 or M3 marrow at the end of no less than 2 prior regimen
    OR
    ii Patients with first relapse ALL failing to achieve response following conventional therapy: M3 marrow following re-induction or M2 or M3 following no less than 2 prior regimen
    OR
    iii Patients with 2 or more relapses of ALL who have received an allogeneic progenitor cell transplant, must:
    a. be at least 6-months post transplant
    b. have good organ function
    c. be stable with no major complications

    4. Must not be eligible for therapy of higher curative potential. Where an alternative therapy has been shown to prolong survival in an analagous population, this should be offered to the patient prior to discussing this study.
    5. Have a Karnofsky Performance Status (KPS) of ≥50 or Lansky Performance Scale of ≥30 .
    6. Provide signed, written informed consent from parent or guardian or young adult patients.
    7. Be able to comply with study procedures and follow-up examinations.
    8. Have normal cardiac function without treatment.
    9. Have adequate organ function as indicated by the following laboratory values, obtained within 7 days prior to registration:

    Inclusion Laboratory Values:
    Parameter Required Value
    Renal
    Serum creatinine <2 × ULN for age
    Hepatic
    Serum bilirubin ≤1.5 × ULN
    AST and ALT ≤10 × ULN
    ULN = Institutional Upper Limit of Normal.






    E.4Principal exclusion criteria
    Patients who meet any of the following criteria will be excluded from study admission:
    1. Received previous treatment with clofarabine.
    2. Patients with isolated extramedullary disease.
    3. Have received prior bone marrow or peripheral blood stem cell transplant within the last 6 months.
    4. Have received prior bone marrow or peripheral blood stem cell transplant more than 6 months ago, but now has compromised organ function.
    5. Have an active, uncontrolled systemic infection considered opportunistic, life threatening, or clinically significant at the time of treatment. Patients who have had a recent (<30 days) history of fungal or bacterial infection or who are receiving therapeutic doses of antibiotics or anti fungals.
    6. Are pregnant or lactating. Male and female patients who are fertile must agree to use an effective means of birth control (i.e., latex condom, diaphragm, cervical cap, etc) to avoid pregnancy.
    7. Have psychiatric disorders that would interfere with consent, study participation, or follow-up.
    8. Have received any other chemotherapy within the previous 2 weeks and must have recovered from acute toxicity of all previous therapy prior to enrolment. Treatment may start earlier, following consultation with the Medical Monitor, if there is evidence of disease relapse or progression prior to that time. Patients who have received growth factor, cytokine support, leukapheresis, or cranial irradiation will be allowed, but must discontinue treatment 24 hours prior to beginning treatment with clofarabine.
    9. Have any other severe concurrent disease, which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
    10. Have recent history of significant renal, hepatic or pulmonary dysfunction, or cardiac dysfunction or on treatment to support cardiac function.
    11. Have CNS disease.
    E.5 End points
    E.5.1Primary end point(s)
    1. The OR rate will be determined by the sum of the number of patients with either a CR or CRp divided by the total number of patients evaluable for response.
    2. The CR rate will be determined by dividing the number of patients with a CR by the total number of patients evaluable for response.
    3. The CRp rate will be determined by dividing the number of patients with a CRp by the total number of patients evaluable for response.
    4. The PR rate will be determined by dividing the number of patients with a PR by the total number of patients evaluable for response.
    5. The MOR rate will be determined by the sum of the number of patients with either a CR, a CRp or a PR divided by the total number of patients evaluable for response.
    6. Overall survival (OS) will be calculated from the date of first dose of clofarabine to the date of death.
    7. Duration of response will be calculated from the date of first documented response to the first documentation of disease relapse (utilising bone marrow aspirate or haematological analysis) or death due to any cause, whichever occurs first.
    8. Safety and tolerability will be evaluated by the incidence, severity (as assessed by the revised NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 3.0 (published 16 April 2003) duration, seriousness, and relationship of adverse events that occur during the treatment and follow-up periods.
    9. BMT/PBSCT rate will be determined by dividing the number of patient receiving BMT/PBSCT by the total number of patient evaluable for response.
    10. Pharmacokinetic parameters will be evaluated in selected patients by population pharmacokinetic methods.
    11. Intracellular clofarabine triphosphate levels of clofarabine will be evaluated in selected patients.
    12. To document the metabolic Pathways that may predict clofarabine sensitivity or resistance.
    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 No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Information not present in EudraCT
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Information not present in EudraCT
    E.7.1.1First administration to humans Information not present in EudraCT
    E.7.1.2Bioequivalence study Information not present in EudraCT
    E.7.1.3Other Information not present in EudraCT
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) Information not present in EudraCT
    E.7.4Therapeutic use (Phase IV) Information not present in EudraCT
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Information not present in EudraCT
    E.8.1.3Single blind Information not present in EudraCT
    E.8.1.4Double blind Information not present in EudraCT
    E.8.1.5Parallel group Information not present in EudraCT
    E.8.1.6Cross over Information not present in EudraCT
    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.8.5The trial involves multiple Member States Yes
    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 Information not present in EudraCT
    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
    Enrollment will continue until 65 patients have been treated with clofarabine and confirmed as evaluable according to IRRP (Independent Response Review Panel) assessment.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months6
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    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) Yes
    F.1.1.4Infants and toddlers (28 days-23 months) Yes
    F.1.1.5Children (2-11years) Yes
    F.1.1.6Adolescents (12-17 years) Yes
    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 Information not present in EudraCT
    F.3.3.1Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2005-09-14. Yes
    F.3.3.2Women of child-bearing potential using contraception Information not present in EudraCT
    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 underage
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state5
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 100
    F.4.2.2In the whole clinical trial 100
    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 Decision2005-10-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2005-10-19
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2007-07-25
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