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    Summary
    EudraCT Number:2019-003462-40
    Sponsor's Protocol Code Number:18IC07
    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:2020-02-28
    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 number2019-003462-40
    A.3Full title of the trial
    Phase 1 , open label study of CRISPR-CAR genome edited T cells (TT52CAR19) in relapsed /refractory B Cell Acute Lymphoblastic Leukaemia
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    TT52CAR19 therapy for B cell acute lymphoblastic leukaemia
    A.3.2Name or abbreviated title of the trial where available
    TT52CAR19 therapy for B-Cell Acute Lymphoblastic Leukaemia (B-ALL) v1
    A.4.1Sponsor's protocol code number18IC07
    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 SponsorGreat Ormond Street Hospital for Children NHS 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 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 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 nameTT52CAR19
    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 INNCAR19+TCRαβ- T cells
    D.3.9.3Other descriptive nameTT52CAR19
    D.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2x10e6
    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 Yes
    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
    Relapsed/ refractory B- cell acute lymphoid leukaemia
    E.1.1.1Medical condition in easily understood language
    B-cell leukaemia
    E.1.1.2Therapeutic area Diseases [C] - Blood and lymphatic diseases [C15]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of the study is to evaluate the safety of TT52CAR19 cell therapy in children with relapsed or refractory B acute lymphoblastic leukaemia (B-ALL).
    E.2.2Secondary objectives of the trial
    The secondary objective is to determine if TT52CAR19 can mediate molecular remission by day 28 and thereby allow patients to proceed to allo-SCT.

    In addition, there are some exploratory objectives:

    • Assess the time to remission, frequency and duration of remission
    • Assess the overall survival, and progression free survival.
    • Assess the immune recovery after TT52CAR19 and after allo-SCT
    • Determine the frequency of GVHD
    • Determine the frequency of viral reactivation (CMV, ADV, EBV)
    • Track the expansion, persistence and elimination of TT52CART19
    • Assess cytokine, ferritin and C-reactive protein levels.
    • Screen for anti-HLA antibody responses.
    • Assess B cell recovery
    • Assess CD19, CD20, CD22 and CD52 expression on leukaemic cells
    • Archive samples for RCL.
    • Monitor DNA signatures of genomic editing in TT52CAR19
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Demographic characteristics
    1. Male or female patients
    2. Age ranging between 6 months and <18years

    Medical and therapeutic criteria
    1. Patients with relapsed (second or subsequent bone marrow relapse or bone marrow relapse after allo-SCT) or refractory (not achieving an initial complete response (CR) after 2 cycles of a standard chemotherapy) CD19-positive B-acute lymphoblastic leukemia

    2. Morphologically confirmed with ≥ 5% leukemic blasts in the bone marrow or a quantifiable MRD load of 1x10-4 (by multiparameter flow cytometry and/or quantitative polymerase chain reaction)

    3. Eligible and fit for allogeneic hematopoietic stem cells transplantation with suitable donor available

    4. Estimated life expectancy ≥ 12 weeks

    5. Lansky (age < 16 years at the time of assent/consent) or Karnofsky (age ≥ 16 years at time of assent/consent) performance status ≥ 50 Eastern Cooperative Oncology Group ECOG performance status < 2
    E.4Principal exclusion criteria
    • Patients/parents unwilling to undergo follow-up
    • Foreseeable poor compliance to the study procedures
    • CD19-negative B-cell leukaemia
    • Evidence of disease progression after cytoreduction
    • Uncontrolled CNS leukeamia or neurological symptoms
    • Absence of suitable HLA matched or mismatched donor
    • Weight < 6 kgs
    • Presence of donor-specific anti-HLA antibodies directed against TT52CAR19 batch
    • GvHD requiring systemic therapy
    • Systemic steroid therapy prednisolone >0.5mg/kg/day
    • Known hypersensitivity to any of the test materials or related compounds
    • Uncontrolled systemic bacterial, fungal, protozoal or viral infection
    • Risk of pregnancy or non compliance with contraception (if applicable). Girls of
    childbearing potential must have been tested negative in a pregnancy test within 7 days prior to inclusion.
    E.5 End points
    E.5.1Primary end point(s)
    The primary objective is to assess safety of TT52CAR19 in paediatric patients with relapsed /refractory B-ALL.
    This will be evaluated by:
    • Clinical examination
    • Measurement of vital signs (blood pressure, heart rate, temperature, respiratory rate)
    • Measurement of standard haematology, biochemistry and coagulation parameters
    • Measurement of oxygen saturation
    • ECG and ECHO if indicated
    • Measurement of Cytokines, Ferritin and CRP levels
    • Viral / bacterial / protozoal infection monitoring
    National Cancer Institute Common Toxicity Criteria for Adverse Event (version V4.3 June 14, 2010) will be used to grade events. Specialized grading scales for CRS and GVHD will be applied.
    E.5.1.1Timepoint(s) of evaluation of this end point
    These primary end points will be evaluated at day 28 post TTCAR19 infusion.
    E.5.2Secondary end point(s)
    The secondary objective is to determine if TTCAR19 can mediate molecular remission by day 28 and thereby allow patients to proceed to allo-SCT.

    There are additional exploratory objectives:

    • Assess the time to remission, frequency and duration of remission
    • Assess the overall survival, and progression free survival.
    • Assess the immune recovery after TTCAR19 and after allo-SCT
    • Determine the frequency of GVHD
    • Determine the frequency of viral reactivation (CMV, ADV, EBV)
    • Track the expansion, persistence and elimination of TTCART19
    • Assess cytokine, ferritin and C-reactive protein levels.
    • Screen for anti-HLA antibody responses.
    • Assess B cell recovery
    • Assess CD19, CD20, CD22 and CD52 expression on leukaemic cells
    • Archive samples for RCL.
    • Monitor DNA signatures of genomic editing in TTCAR19
    E.5.2.1Timepoint(s) of evaluation of this end point
    These secondary end points will be evaluated at day 28 post TTCAR19 infusion.
    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 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 Yes
    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) No
    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 Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.4.1Number of sites anticipated in Member State concerned1
    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
    LVLS
    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
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 10
    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) Yes
    F.1.1.4.1Number of subjects for this age range: 4
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 3
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 3
    F.1.2Adults (18-64 years) No
    F.1.2.1Number of subjects for this age range: 0
    F.1.3Elderly (>=65 years) No
    F.1.3.1Number of subjects for this age range: 0
    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 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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Children and infants
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state10
    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)
    The study treatment consists of a single administration of TT52CAR19 product. No further administration is expected. Patients will be followed for 3 years after TT52CAR19 administration.
    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 Decision2020-01-27
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-03-30
    P. End of Trial
    P.End of Trial StatusGB - no longer in EU/EEA
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