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    Summary
    EudraCT Number:2015-002231-18
    Sponsor's Protocol Code Number:RMHCAN1104
    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:2015-09-23
    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 number2015-002231-18
    A.3Full title of the trial
    A Phase I/IIa Study of Targeted Radiotherapy alone for Stem Cell Transplant Conditioning in Systemic AL Amyloidosis
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase I/IIa (early phase) Study of Targeted Radiotherapy alone for Stem Cell Transplant Conditioning in Systemic AL Amyloidosis
    A.3.2Name or abbreviated title of the trial where available
    Targeted Radiotherapy for AL-Amyloidosis –‘TRALA’
    A.4.1Sponsor's protocol code numberRMHCAN1104
    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 Southampton Hospital NHS Foundation Trust
    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 supportLeukaemia and Lymphoma Research fund
    B.4.2CountryUnited Kingdom
    B.4.1Name of organisation providing supportAmyloidosis Research Fund (UCL)
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUniversity Southampton Hospital NHS Trust
    B.5.2Functional name of contact pointDr Kim Orchard
    B.5.3 Address:
    B.5.3.1Street AddressHaematology Department
    B.5.3.2Town/ citySouthampton
    B.5.3.3Post codeSO16 6YD
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number02381204163
    B.5.6E-mailkim.orchard@uhs.nhs.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 nameCHX-A"-DTPA-Anti-CD66
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMP
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCHX A"-DTPA anti-CD66 antibody
    D.3.9.4EV Substance CodeAS4
    D.3.10 Strength
    D.3.10.1Concentration unit MBq/kg megabecquerel(s)/kilogram
    D.3.10.2Concentration typeequal
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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 Yes
    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.IMP: 2
    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 nameIndium­ 111 ­labelled Anti­-CD66
    D.3.4Pharmaceutical form 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.3.8INN - Proposed INNIndium 111-radiolabelled anti-CD66
    D.3.9.4EV Substance CodeAS2
    D.3.10 Strength
    D.3.10.1Concentration unit MBq/kg megabecquerel(s)/kilogram
    D.3.10.2Concentration typeequal
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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 Yes
    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.IMP: 3
    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 nameyttrium-90 radiolabelled anti-CD66 antibody
    D.3.4Pharmaceutical form 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.3.8INN - Proposed INNYttrium­90 radiolabelled anti­CD66
    D.3.9.4EV Substance CodeAS3
    D.3.10 Strength
    D.3.10.1Concentration unit MBq/kg megabecquerel(s)/kilogram
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number2 to 5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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 Yes
    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
    AL-Amyloidosis
    E.1.1.1Medical condition in easily understood language
    Amyloidosis is a disorder of protein folding in which normally soluble proteins are deposited as abnormal, insoluble fibrils that progressively disrupt tissue structure and impair function.
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.0
    E.1.2Level LLT
    E.1.2Classification code 10024460
    E.1.2Term Light chain disease myeloma associated
    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
    This trial is a phase I/IIa study to assess the use of a [90Y]-labelled anti-CD66 as the sole conditioning prior to autologous stem cell transplant conditioning in patients with AL-amyloidosis.

    The main objective will be to determine the safety and toxicity associated with the use of the [90Y]-labelled anti-CD66 as measured by CTCAE version 4.0 criteria and stem cell engraftment and hence establish the maximum tolerated radiation dose (MTD) over three infused radiation activity levels.
    E.2.2Secondary objectives of the trial
    In addition the study will allow the assessment of clonal response (as measured by serial FLC assay) and by using established, validated methods of FLOW cytometry to measure the change in malignant plasma cell population. Disease response, cardiac recovery, time to progression and overall survival will also be reviewed, whilst determining the engraftment status of patients.
    Finally the study will allow the assessment of the dosimetry model previously developed in Phase I and II trials in this patient group.

    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    The main inclusion criteria is patients with systemic AL-amyloidosis with an indication for treatment who satisfy all standard transplant inclusion criteria (good organ function, no significant heart involvement, good performance status).

    • Aged ≥18 years.
    • Have a diagnosis of systemic AL-amyloidosis, either as a new diagnosis or recurrent disease.
    • Measurable clonal plasma cell dyscrasia.
    • Amyloid related organ dysfunction or organ syndrome.
    • Estimated life expectancy of at least 6 months (as defined at trial entry).
    • Sufficient stem cells for two transplant procedures .
    • Bone Marrow (BM) cellularity >20%.
    • Eligible for ASCT in AL amyloidosis defined as fulfilling all of the following criteria :
    o ECOG Performance Status of 0 or 1
    o Cardiac troponin-T <0.07 µg/L
    o NYHA heart failure class of <3
    o No more than 3 organs involved by amyloidosis by consensus guidelines.
    o Creatinine clearance or isotope GFR ≥30ml/min.
    o Bilirubin ≤1.5 times and alkaline phosphatase ≤3 x upper limit of normal.
    o AST or ALT <2.5 x upper limit of normal range.
    o Mean left ventricular wall thicknesses of <16mm by echocardiography.
    o Absence of clinically important amyloid related autonomic neuropathy .
    o Absence of clinically important amyloid related gastro intestinal haemorrhage.
    • Capable of providing written, informed consent.
    • Women of child bearing potential should use adequate forms of contraception.
    o Intrauterine Device (IUD)
    o Hormonal based contraception (pill, contraceptive injection etc.)
    o Double Barrier contraception (condom and occlusive cap e.g. diaphragm or cervical cap with spermicide)
    o True abstinence
    E.4Principal exclusion criteria
    Patients with poor performance, advanced organ involvement or significant cardiac involvement will be excluded from the study.

    Patients with the following characteristics are ineligible for this study:
    • Overt symptomatic multiple myeloma.
    • Amyloidosis of unknown or non AL type.
    • Localised AL-amyloidosis (in which amyloid deposits are limited to a typical single organ, for example the bladder or larynx, in association with a clonal proliferative disorder within that organ).
    • Trivial or incidental AL amyloid deposits in the absence of a significant amyloid related organ syndrome (e.g., isolated carpal tunnel syndrome).
    • NYHA Class III or IV heart failure (appendix 1).
    • Liver involvement by amyloid causing bilirubin >1.5 times upper limit of normal.
    • Concurrent active malignancies, except surgically removed basal cell carcinoma of the skin or other in situ carcinomas.
    • Pregnant, lactating or unwilling to use adequate contraception as listed above
    • Intolerance / sensitivity to any of the study drugs.
    • Known positive Human anti-murine antibodies (HAMA).
    • Unable to provide written informed consent
    • Involved in another IMP trial
    E.5 End points
    E.5.1Primary end point(s)
    Primary objective is: Safety and toxicity of using [90Y]-anti-CD66 as the sole conditioning prior to autologous stem cell transplantation for AL-amyloidosis.
    Primary Outcome measure is: Specific organ toxicity as defined in CTCAE ver 4.0. Overall number of Serious Adverse Events, Serious Unexpected Adverse Events determined as causally related to the radiolabelled anti-CD66.
    E.5.1.1Timepoint(s) of evaluation of this end point
    at completion of study
    E.5.2Secondary end point(s)
    1. Disease response as determined by changes in the free light chain assay (FLCa) pre and post [90Y]-labelled anti-CD66 and post transplantation.
    2. Clonal plasma cell population as determined by FLOW cytometry pre and post transplantation (D100)
    3. NT-proBNP levels pre and post (D100) therapy
    4. Assessment of TTP and OS.
    5. Comparison of organ dosimetry from previous trials using the same antibody vector.
    6. Tablation of platelet and neutrophil engraftment.



    HAMA assay results from samples taken at defined intervals post transplantation
    E.5.2.1Timepoint(s) of evaluation of this end point
    at completion of trial
    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) Yes
    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
    Orchard et al have reported targeting with the anti-CD66 in previous Phase I
    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 concerned5
    E.8.5The trial involves multiple Member States No
    E.8.5.1Number of sites anticipated in the EEA4
    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
    United Kingdom
    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
    Patient recruitment into the trial will end after the last patient reaches the day +100 post transplant time-point.
    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 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: 18
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 18
    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 state18
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 18
    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)
    Patients will not receive any post trial IMP as this is a one off treatment. They will return to standard follow up at their treating transplant centre.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.3.4Network Country United Kingdom
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2015-11-16
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-12-01
    P. End of Trial
    P.End of Trial StatusGB - no longer in EU/EEA
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