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    Summary
    EudraCT Number:2019-002930-35
    Sponsor's Protocol Code Number:Uni-Koeln-3903
    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:2020-08-27
    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 number2019-002930-35
    A.3Full title of the trial
    Phase II trial of TisaGenlecleucel in Elderly Patients with First-Relapsed or Primary Refractory Agressive B-cell Non-Hodgkin Lymphoma
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    CAR T cell treatment in Elderly Patients with First-Relapsed or Primary Refractory B-cell Non-Hodgkin Lymphoma
    A.3.2Name or abbreviated title of the trial where available
    TIGER-CTL019
    A.4.1Sponsor's protocol code numberUni-Koeln-3903
    A.5.4Other Identifiers
    Name:ClinicalTrials.govNumber:NCT04161118
    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 SponsorUniveristy of Cologne
    B.1.3.4CountryGermany
    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 supportNovartis
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUniversity Hospital Cologne
    B.5.2Functional name of contact pointCologne Cancer Study Group
    B.5.3 Address:
    B.5.3.1Street AddressKerpener Straße 62
    B.5.3.2Town/ cityCologne
    B.5.3.3Post code50937
    B.5.3.4CountryGermany
    B.5.4Telephone number004922147896533
    B.5.6E-mailkatrin.von-schimmelmann@uk-koeln.de
    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 Kymriah®
    D.2.1.1.2Name of the Marketing Authorisation holderNovartis
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 nameTisagenlecleucel
    D.3.4Pharmaceutical form Injection
    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 INNTisagenlecleucel
    D.3.9.3Other descriptive nameKymriah
    D.3.9.4EV Substance CodeSUB177825
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number0,6 to 6,0x 10^8
    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) 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
    malignant disease of lymphnodes especially refractory and non-responding aggressive non Hodgkin lymphoma; Diffuse large B cell lymphoma (DLBCL)
    E.1.1.1Medical condition in easily understood language
    refractory and non-responding aggressive B-cell Non-Hodgkin’s Lymphoma (aNHL)
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 23.0
    E.1.2Level PT
    E.1.2Classification code 10029601
    E.1.2Term Non-Hodgkin's lymphoma refractory
    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 evaluate efficacy of treatment with tisagenlecleucel in elderly patients with r/r aNHL
    E.2.2Secondary objectives of the trial
    - To explore efficacy, safety, and feasibility of the experimental therapy
    - Quality of life during CAR-T-cell treatment
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Written, signed and dated informed consent
    2. Patients with first relapse of aggressive B-cell Non-Hodgkin’s Lymphoma (aNHL) within 365 days after rituximab- and anthracycline-containing first-line immunochemotherapy or aNHL refractory to respective 1st-line therapy (no achievement of a CR or PR) who are ineligible for either autologous or allogeneic stem cell transplantation, defined as age > 65 years, or > 60 years old with HCT-CI score >2 and not older than 80 years
    3. Histologically confirmed aNHL as defined by a list of subtypes
    4. Measurable disease:
    Nodal lesions >15 mm in the long axis, regardless of the length of the short axis,
    and/or
    Extranodal lesions (outside lymph node or nodal mass, but including liver and spleen) >10 mm in long AND short axis
    5. ECOG performance status 0-2
    6. Adequate organ function:
    o Serum creatinine of ≤1.5 x ULN, or estimated glomerular filtration rate (GFR) ≥ 30mL/min/1.73m2
    o Hepatic function defined as:
     ALT and AST ≤ 5 × ULN, except for aNHL-related functional impairment.
     Bilirubin ≤ 2.0 mg/dL except for patients with Gilbert syndrome who may be included if their total bilirubin is ≤ 3.0 × ULN and direct bilirubin ≤ 1.5 × ULN OR for aNHL-related functional impairment
    o Adequate bone marrow function
    o Minimum level of pulmonary function
    7. Life expectancy of more than six months
    8. Women have to be in menopausal or post-menopausal status or confirmed as not having potential on childbearing. Male participants with female partners of childbearing potential are eligible to participate if they agree to contraceptive methods
    E.4Principal exclusion criteria
    1. Patients with Richter’s transformation, Burkitt lymphoma, and PCNSL
    2. Prior treatment with anti-CD19 therapy, adoptive T cell therapy, or any prior gene therapy product
    3. Treatment with any lymphoma-directed second line anticancer therapy prior to enrollment with the exception of intermittent steroid therapy. After enrollment, bridging therapy is permitted for disease control
    4. Patients with active CNS involvement
    5. Prior autologous or allogeneic stem cell transplantation (HSCT)
    6. Active hepatitis B, hepatitis C, or hepatitis E infection
    7. HIV-positive patients
    8. Uncontrolled acute life-threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
    9. Cardiac dysfunction
    10. Previous or concurrent malignancy with the exceptions
    11. Women of childbearing potential (WOCBP), pregnant or lactating women
    12. Intolerance to the excipients of the tisagenlecleucel cell product
    13. Active or history of inflammatory disorders or autoimmune disease that required systemic steroids or immunosuppressive medications, with exception of vitiligo or resolved childhood asthma
    14. Active tuberculosis
    15. Exposure to any investigational agent(s) within 4 weeks prior to study entry
    16. Chemotherapy less than 2 weeks before leukapheresis
    17. Simultaneous radiotherapy to tisagenlecleucel infusion (radiotherapy between leukapheresis and day -6 before tisagenlecleucel infusion is permitted)
    18. Ongoing necessity for systemic corticosteroids >10mg daily prednisone equivalent. Inhaled or topical steroids and adrenal replacement steroid doses > 10mg daily prednisone equivalent are permitted in the absence of active autoimmune disease
    19. History of active primary immunodeficiency
    20. Major surgery (defined as opening at least one body cavity) within 4 weeks prior to study entry
    21. History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening CT scan
    22. Patients with a history of prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4 antibodies, other immune checkpoint inhibitors
    23. Prior treatment with any anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy
    24. Current treatment within another therapeutic clinical trial with experimental and not approved drugs and treatment combinations
    25. Patient’s lack of accountability and inability to appreciate the nature, meaning and consequences of the trial and to formulate his/her own wishes correspondingly
    26. Non-compliance
    27. Patients who have a relationship of dependence or employer-employee relationship to the sponsor or the investigator
    28. Committal to an institution on judicial or official order
    E.5 End points
    E.5.1Primary end point(s)
    Complete metabolic response (CMR) rate
    E.5.1.1Timepoint(s) of evaluation of this end point
    12 weeks after tisagenlecleucel infusion
    E.5.2Secondary end point(s)
    1. Incidence and severity of adverse events (AEs)
    2. Progression-free survival (PFS) rates at 1 and 2 year(s)
    3. Overall survival (OS) rates at 1 and 2 year(s)
    4. Duration of response (DOR)
    5. Incidence of immunogenicity to tisagenlecleucel
    6. Overall response Rate (ORR), defined as the proportion of patients reaching CR or PR according to central review up until the restaging 12 weeks after treatment with tisagenlecleucel
    7. ORR according to local findings
    8. Rates and reasons for drop-outs prior to tisagenlecleucel infusion will be reported for the ITT
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. from screening until end of study
    2. at 1 and 2 years after tisagenlecleucel infusion
    3. at 1 and 2 years from time of Screening
    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 No
    E.6.7Pharmacodynamic No
    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
    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.8.2.4Number of treatment arms in the trial1
    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 concerned10
    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 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
    LPLV: last patient last visit
    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 months2
    E.8.9.1In the Member State concerned 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: 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 state28
    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 have a follow-up visit every 3 months for 24 months if patient finishes clinical trial without any disease progression.
    Patients who drop out due to disease Progression will recieve a Standard of care (SOC) treatment.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation Centrum für Integrierte Onkologie (CIO)
    G.4.3.4Network Country Germany
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2021-02-22
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-12-17
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2023-02-24
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