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    Summary
    EudraCT Number:2012-003631-36
    Sponsor's Protocol Code Number:RG_12-124
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:GB - no longer in EU/EEA
    Date on which this record was first entered in the EudraCT database:2015-03-10
    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 ConcernedUK - MHRA
    A.2EudraCT number2012-003631-36
    A.3Full title of the trial
    CALiBRe: Assessment of the Mechanism of Action of idelalisib (CAL-101) in B-cell Receptor Pathway Inhibition in CLL
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    CALiBRe: Assessment of the Mechanism of Action of idelalisib (CAL-101) in B-cell Receptor Pathway Inhibition in CLL
    A.3.2Name or abbreviated title of the trial where available
    Calibre
    A.4.1Sponsor's protocol code numberRG_12-124
    A.5.1ISRCTN (International Standard Randomised Controlled Trial) NumberISRCTN52057158
    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 SponsorUniversity of Birmingham
    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 support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCancer Research UK Clinical Trials Unit
    B.5.2Functional name of contact pointFrancesca Yates
    B.5.3 Address:
    B.5.3.1Street AddressVincent Drive
    B.5.3.2Town/ cityBirmingham
    B.5.3.3Post codeB15 2TT
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number01213717867
    B.5.5Fax number01213717864
    B.5.6E-mailcalibre@trials.bham.ac.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 Yes
    D.2.1.1.1Trade name Zydelig
    D.2.1.1.2Name of the Marketing Authorisation holderGilead Sciences International
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberORPHA356374
    D.3 Description of the IMP
    D.3.1Product nameZydelig
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNIdelalisib formerly CAL-101, GS-1101
    D.3.9.1CAS number 870281-82-6
    D.3.9.2Current sponsor codeIdelalisib
    D.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100 to 150
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Chronic lymphocytic leukaemia
    E.1.1.1Medical condition in easily understood language
    Blood cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10068852
    E.1.2Term B-cell chronic lymphocytic leukaemia
    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 investigate the mechanism of action of idelalisib
    E.2.2Secondary objectives of the trial
    To assess the biological response to idelalisib

    To assess 1 and 2 year progression free survival

    To assess the 1 and 5 year overall and disease free survival of patients
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Title: Effect of idelalisib on the release proliferation and loss rate of CLL cells.

    The key objective of this study is to investigate tumour kinetics during idelalisib therapy.
    E.3Principal inclusion criteria
    1. Chronic lymphocytic leukaemia requiring therapy
    2. Relapsed/refractory CLL defined as any of the following:
    - Failure to achieve a response (CR or PR) to, or progression during or after, ibrutinib (or an alternative Btk inhibitor)
    Or:
    - Patients who are unable to tolerate ibrutinib (or an alternative BTK inhibitor) or in whom it is contraindicated.
    _And_ where at least one of the following criteria apply
    • Patients with CLL with deletion of chromosome 17p who have failed at least one previous therapy
    • Failure to achieve a response (CR or PR by IWCLL criteria) to a purine analogue alone or in combination with chemotherapy, or:
    • Relapse within 6 months of responding to a purine analogue alone or in combination with chemotherapy, or:
    • Relapse at any time after fludarabine, cyclophosphamide and rituximab (FCR) or chemotherapy plus rituximab (or an alternative anti-CD20 antibody):
    3. ECOG performance status (PS) of 0, 1, or 2 (see Appendix 5).
    4. Life expectancy of at least 6 months
    5. Prepared to undergo the stipulated investigations within the trial (including bone marrow examinations)
    6. Age ≥18
    7. Able to give informed consent
    E.4Principal exclusion criteria
    1. Previously untreated for CLL
    2. Unwilling to undergo the protocol assessments including the bone marrow assessments
    3. Active infection at the time of registration, history of chronic or recurrent infection
    4. Other severe, concurrent (particularly cardiac or pulmonary) diseases or mental disorders that could interfere with their ability to participate in the study
    5. Use of prior investigational agents within 6 weeks
    6. Pregnancy or lactation
    7. Unwilling to use appropriate contraception during and for 30 days following treatment
    8. CNS involvement with CLL
    9. Mantle cell lymphoma
    10. Known HIV positive
    11. Active or prior Hepatitis B or C
    12. Active secondary malignancy excluding basal cell carcinoma
    13. Persisting severe pancytopenia (neutrophils <0.5 x109/L) or transfusion dependent anaemia unless due to direct marrow infiltration by CLL. This is to be confirmed via bone marrow biopsy.
    14. Active haemolysis (not controlled with prednisolone at 20mg or less)
    15. Hypersensitivity to idelalisib or to any of the excipients listed in the Summary of Product Characteristics (SmPC)
    16. Previous treatment with idelalisib or another PI3K inhibitor
    E.5 End points
    E.5.1Primary end point(s)
    •Proportion of patients achieving MRD-negative remission by IWCLL criteria (depletion of CLL below 0.01% in the peripheral blood and bone marrow)
    E.5.1.1Timepoint(s) of evaluation of this end point
    6 months
    E.5.2Secondary end point(s)
    • CLL cell levels as a percentage of total leucocytes in the bone marrow (BM) and absolute counts in the peripheral blood (PB).
    • The proportion of patients with >5%, 0.5-5%, <0.5% CLL cells in cell cycle (expressing Ki67) in the peripheral blood and bone marrow after 6-9 months of idelalisib.
    • Change in the expression levels of CD10, CD103, CD11c, CD195, CD196, CD20, CD200, CD22, CD23, CD25, CD27, CD305, CD31, CD38, CD39, CD43, CD49d, CD5, CD79b, CD81, CD95, IgD, IgG, or IgM on CLL cells relative to baseline by more than 50% and at least 500 arbitrary units in median fluorescence intensity.
    • Best disease response: Complete Remission (CR); Complete Remission with incomplete marrow recovery (Cri) or Partial Remission (PR), to treatment within the first 6 months of treatment assessed according to the IWCLL Response Criteria (revised 2008)
    • 1 and 2 year progression free survival for relapsed/refractory and treatment naïve patients defined as time from date of registration to date of progression (per the 2008 IWCLL criteria) or death from any cause.
    • 1 and 5 year overall survival for relapsed/refractory and treatment naïve patients, defined as the time from date of registration to the date of death from any cause.
    •Toxicity of idelalisib within 6 months.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Up to 5 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 No
    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
    To investigate the mechanistic action and biological response to idelalisib
    E.7.2Therapeutic exploratory (Phase II) Yes
    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 concerned13
    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 No
    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 end of the trial will be six months from the last data capture. This will allow sufficient time for the completion of protocol procedures, data collection and input.
    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 months11
    E.8.9.1In the Member State concerned days31
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months11
    E.8.9.2In all countries concerned by the trial days31
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number of subjects for this age range: 0
    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) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 0
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 20
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 20
    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 No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    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 state40
    F.4.2 For a multinational trial
    F.4.2.2In the whole clinical trial 0
    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)
    All patients will remain on study treatment for at least 12 months unless their disease progresses, they become MRD negative, or withdraw from study drug treatment for any reasons such as toxicity. After 12 months of study treatment patients that have stable disease or have maintained a response on treatment will be given the option to either continue idelalisib therapy as part of a separate industry/academic study if available, or continue receiving idelalisib on the CALiBRe study protocol.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2015-02-10
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-01-22
    P. End of Trial
    P.End of Trial StatusGB - no longer in EU/EEA
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