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    The EU Clinical Trials Register currently displays   43857   clinical trials with a EudraCT protocol, of which   7284   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:2014-003111-10
    Sponsor's Protocol Code Number:D-00272-CT2014002
    National Competent Authority:Germany - PEI
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2014-12-23
    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 ConcernedGermany - PEI
    A.2EudraCT number2014-003111-10
    A.3Full title of the trial
    A single arm Phase I/II study of the safety and efficacy of gene-modified WT1 TCR therapy in patients with myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML) who have failed to achieve or maintain an IWG defined response following hypomethylating agent therapy.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Phase I/II study of the safety and efficacy of gene-modified WT1 TCR therapy in patients with myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML)
    A.3.2Name or abbreviated title of the trial where available
    A Phase I/II study of gene-modified WT1 TCR therapy in MDS & AML patients
    A.4.1Sponsor's protocol code numberD-00272-CT2014002
    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 SponsorCell Medica Ltd
    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 supportCell Medica Ltd
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCell Medica Ltd
    B.5.2Functional name of contact pointAlex Bloom
    B.5.3 Address:
    B.5.3.1Street Address1 Canal Side Studios, 8-14 St Pancras Way
    B.5.3.2Town/ cityLondon
    B.5.3.3Post codeNW1 0QG
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number442075544076
    B.5.5Fax number442071834745
    B.5.6E-mailalex.bloom@cellmedica.co.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 nameWT1 TCR Transduced T Cells
    D.3.2Product code D-00272
    D.3.4Pharmaceutical form Solution for injection/infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous drip use (Noncurrent)
    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) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Yes
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product Yes
    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
    Acute myeloid leukaemia and myelodysplastic syndromes in adults
    E.1.1.1Medical condition in easily understood language
    Acute myeloid leukaemia and myelodysplastic syndromes in adults
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10000880
    E.1.2Term Acute myeloid leukaemia
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10028533
    E.1.2Term Myelodysplastic syndrome
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To examine the safety and proportion of subjects achieving one or more IWG (2006) response criteria (within 12 months) following gene-modified WT1 TCR therapy
    E.2.2Secondary objectives of the trial
    • To examine the safety and tolerability of gene-modified WT1 TCR therapy
    • To evaluate the clinical efficacy of gene-modified WT1 TCR therapy
    • To confirm the technical feasibility of gene-modified WT1 TCR therapy in subjects with myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML) with low blast count
    • To determine the persistence and function of WT1 TCR-transduced T cells
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Subjects must meet all of the following inclusion criteria to be eligible for enrolment into the trial:
    Diagnosis and main criteria for admission to screening phase of trial:
    The trial will recruit subjects with MDS or AML who have received hypomethylating agent therapy (at least 6 cycles of azacitidine or 4 cycles of decitabine), and are EITHER:
    • Relapsed, defined as failing to maintain an initial IWG response
    OR
    • Stable, defined as failing to achieve an IWG response

    IWG response is defined as complete remission; partial remission; marrow complete remission; cytogenetic response; stable disease with haematological improvement.

    Subjects who have received hypomethylating agent therapy as part of a combination regimen may be eligible after discussion with the Sponsor.


    1. Subjects aged 18 years or older who have a diagnosis of, EITHER:
    • MDS with an IPSS of intermediate -2, or high and one of the following FAB types:
    o Refractory anaemia with excess blasts (RAEB)
    o Chronic myelomonocytic leukaemia (CMML) with at least 10% bone marrow blasts (WHO CMML II)
    OR
    • AML (diagnosed according to WHO classification 2008 revision)
    2. Subjects with documented HLA-A*0201 positive serotype
    3. Subjects positive for WT1 over expression at 50 copies WT1 transcript per 104 ABL copies assessed via analysis of peripheral venous blood samples
    4. Subjects with less than 30 per cent bone marrow blasts
    5. Subjects with relapsed disease must have less than 5 per cent peripheral blasts
    6. Subjects with stable disease must have less than 10 per cent peripheral blasts
    7. Subjects with less than a doubling of bone marrow blast count between the start of hypomethylating agent therapy and the date of screening
    8. Subjects to complete screen 1 visit within a minimum of 28 days and maximum of 90 days since completion of azacitidine or decitabine therapy . Subjects who have exceeded the 90 day window may be eligible after discussion with the Sponsor.
    9. Subjects with ECOG status 0, 1 or 2
    10. Subjects who have at least one cytopenia (ANC < 1000/µL, platelet count < 75,000/µL, Hgb <11g/dL or RBC transfusion dependence)
    11. Willing, able and available for collection of Peripheral Blood Mononuclear Cells (PBMC)/ T cells by leukapheresis
    12. Subjects must understand and be able, willing and likely to fully comply with all trial procedures and restrictions
    13. Written, signed and dated informed consent to participate in the study must be given by the subject or legally authorised representative in accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E6, and applicable regulations, before completing any trial-related procedures.
    E.4Principal exclusion criteria
    Subjects presenting with any of the following criteria will not be included in the trial:

    1. Subjects with CMML who have a white blood cell count > 13000 million / L
    2. Subjects with peripheral blood total lymphocyte count < 500 million / L
    3. Subjects with acute promyelocytic leukaemia (FAB M3 Classification)
    4. Subjects who are a current candidate for allogeneic stem cell transplantation and have a suitable donor
    5. Subjects requiring concurrent use of systemic steroids at time of leukapheresis or in a 14 day window around time of cell infusion
    6. Subjects who have an immediate or anticipated need for induction chemotherapy, or are receiving agents that could confound the interpretation of trial results, in the opinion of the Investigator
    7. Subjects with any active malignancy, except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast
    8. Subjects with uncontrolled intercurrent illness including, but not limited to, clinically significant ischaemic heart disease, cardiac arrhythmia, concurrent congestive heart failure or prior history of New York Heart Association (NYHA) class III/ IV cardiac disease, uncontrolled hypertension (defined as systolic pressure ≥160 mmHg and/or diastolic pressure ≥110 mmHg) or clinically significant pulmonary disease
    9. Subjects with active infection (bacterial, viral or fungal) which is clinically significant at the time of leukapheresis or cell infusion
    10. Subjects with known history of Human Immunodeficiency Virus (HIV), Hepatitis C virus (HCV) or Hepatitis B virus (HBV) or who test positive for HTLV or Syphilis. Subjects who are positive for HIV, Hepatitis B or Hepatitis C must have a negative polymerase chain reaction (PCR) result prior to leukapheresis
    11. Subjects with active auto-immune disease including, but not limited to, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, Sjögren’s syndrome, sarcoidosis, vasculitis, polymyositis, psoriasis, relapsing polychondritis or glomerulonephritis)
    12. Subjects with clinically significant non-haematologic toxicity after prior chemotherapy higher than grade 1 per Common Terminology Criteria for Adverse Events (CTCAE) (v 4.0)
    13. Subjects with clinically significant renal and liver parameters, defined as total bilirubin ≥1.5 mg/dL not related to haemolysis or Gilbert's disease; alanine transaminase (ALT)/aspartate transaminase (AST) ≥2.5 x upper limit of normal (ULN) and/or serum creatinine ≥2.0 mg/dL
    14. Subjects who require haemodialysis or peritoneal dialysis
    15. Subject of childbearing potential unable to take adequate contraceptive precautions, has a positive pregnancy test result at screening, is otherwise known to be pregnant or is currently breast-feeding
    16. Male subjects unwilling or unable to use adequate contraceptive precautions (barrier method or abstinence) at screening and throughout the trial
    17. Subjects who have undergone major surgery without full recovery within last 28 days prior to screening
    18. Subjects with known hypersensitivity to fludarabine, methylprednisolone or IL-2
    19. Subjects who have participated in any other interventional clinical trial or received treatment with any investigational agent, chemotherapy, or immunotherapy within 28 days prior to infusion. Growth factors and erythropoietin allowed before and during the trial as clinically indicated
    20. Subjects who have received previous treatment with gene modified T cell therapy
    21. Subjects who have received radiotherapy within 14 days prior to screening
    22. Subject who has a severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this trial
    E.5 End points
    E.5.1Primary end point(s)
    Efficacy
    Proportion of subjects achieving one or more of the following IWG response criteria within 12 months of administration of gene-modified WT1 TCR T cell therapy: complete remission; partial remission; marrow complete remission; cytogenetic response; haematological improvement

    Safety
    Suspected Unexpected Serious Adverse reactions
    E.5.1.1Timepoint(s) of evaluation of this end point
    Efficacy
    Within 12 months of administration of gene-modified WT1 TCR T cell therapy
    E.5.2Secondary end point(s)
    Efficacy

    • Proportion of subjects achieving a Haematological Improvement (HI):
    1. Erythroid response
    2. Platelet response
    3. Neutrophil response
    • Overall Remission Rate (complete remission & partial remission)
    • Proportion of subjects achieving marrow complete remission
    • Proportion of subjects achieving complete or partial cytogenetic response
    • Proportion of subjects achieving a molecular response
    • Proportion of subjects achieving IWG defined response of stable disease and duration of stable disease
    • Proportion of subjects with MDS transforming to AML and time to AML transformation
    • Progression Free Survival (PFS)
    • Event Free Survival (EFS)
    • Overall Survival (OS)


    Safety
    • Adverse events (AEs)
    • Clinical laboratory parameters
    • Tolerability

    E.5.2.1Timepoint(s) of evaluation of this end point
    Efficacy
    Within 12 months of administration of gene-modified WT1 TCR T cell therapy
    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 Yes
    E.6.13.1Other scope of the trial description
    Pharmacodynamics
    - Persistence of WT1 TCR-transduced T cells by Vβ2.1 and tetramer staining
    - PCR for Vβ2.1 and TCR-vector fragments

    Exploratory
    - Functionality and phenotype of WT1 TCR-transduced T cells
    - WT1 transcript analysis in AML/MDS cells
    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
    Phase I/II safety and effiacy study
    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 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) 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 concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA8
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years4
    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.1.1.1In 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) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 10
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 30
    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 No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 40
    F.4.2.2In the whole clinical trial 40
    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)
    Supportive care and the Investigator is responsible to make provisions for long-term follow-up (5 years or as agreed with the relevant Competent Authority, or Ethics Committee) for subjects surviving beyond the completion of the trial
    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 Decision2016-06-01
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-03-18
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
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