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The European Union Clinical Trials Register   allows you to search for protocol and results information on:
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    The EU Clinical Trials Register currently displays   43931   clinical trials with a EudraCT protocol, of which   7307   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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    EudraCT Number:2016-000296-24
    Sponsor's Protocol Code Number:CL1-68587-002
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2017-10-20
    Trial results View results
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    A. Protocol Information
    A.1Member State ConcernedFrance - ANSM
    A.2EudraCT number2016-000296-24
    A.3Full title of the trial
    Phase I, open label, dose-escalation study to evaluate the safety, expansion and persistence of a single dose of UCART19 (allogeneic engineered T-cells expressing anti-CD19 chimeric antigen receptor), administered intravenously in patients with relapsed or refractory CD19 positive B-cell acute lymphoblastic leukaemia (B-ALL)).
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to evaluate the safety and tolerability of ascending doses of UCART19 given as a single infusion in patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukaemia (B-ALL) and to determine the maximum tolerated dose (MTD).
    A.3.2Name or abbreviated title of the trial where available
    CALM study
    A.4.1Sponsor's protocol code numberCL1-68587-002
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02746952
    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 SponsorInstitut de Recherches Internationales Servier (I.R.I.S)
    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 supportADIR
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationInstitut de Recherches Internationales Servier
    B.5.2Functional name of contact pointClinical Studies Department
    B.5.3 Address:
    B.5.3.1Street Address50 Rue Carnot
    B.5.3.2Town/ citySuresnes
    B.5.3.3Post code92284
    B.5.4Telephone number+33 155 7243 66
    B.5.5Fax number+33 155 7254 12
    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 nameUCART19
    D.3.2Product code S68587
    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 INNCD19CAR/RQR8+_TCRαβ-_T-cells
    D.3.9.2Current sponsor codeS68587
    D.3.9.3Other descriptive nameUCART19
    D.3.9.4EV Substance CodeSUB180949
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number6.10^5 to 2.10^7
    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. cell therapy medicinal product No
    D. therapy medical product Yes
    D. Engineered Product No
    D. ATIMP (i.e. one involving a medical device) No
    D. on Advanced therapies (CAT) has issued a classification for this product Yes
    D. classification and reference numberGene therapy medicinal product EMA/132648/2014
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Patients with relapsed or refractory CD19 positive B-cell acute lymphoblastic leukaemia (B-ALL).
    E.1.1.1Medical condition in easily understood language
    Patients with B-cell acute lymphoblastic leukaemia (B-ALL) that have relapsed or for whom previous treatments have not worked.
    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 LLT
    E.1.2Classification code 10060390
    E.1.2Term Leukaemia lymphoblastic acute
    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
    To evaluate the safety and tolerability of ascending doses of UCART19 given as a single infusion in patients with relapsed/refractory (R/R) acute lymphoblastic leukaemia (ALL) and to determine the maximum tolerated dose (MTD).
    E.2.2Secondary objectives of the trial
    To assess the anti-leukaemic activity specifically
    - rate of objective response at Day 28, Day 84 and overall response
    - duration of response, time to response, disease-specific survival and progression-free survival.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Male or female participant
    2. Age ≥ 16 years
    3. Patient with relapsed or refractory CD19 positive B-acute lymphoblastic leukaemia (B-ALL).
    4. Estimated life expectancy ≥ 12 weeks (according to investigator’s judgement).
    5. Eastern Cooperative Oncology Group (ECOG) performance status < 2
    6. Adequate organ functions including renal and hepatic function based on the last assessment performed within the Screening Period, defined as:
    - creatinine clearance ≥ 30 mL/min (assessed as GFR using the Cockcroft & Gault formula)
    - Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 3 x ULN (upper limit of normal)
    - Total bilirubin < 1.5 x ULN (Except Gilbert’s Syndrome confirmed by UGT1A1 gene mutation)
    7. Women of childbearing potential must have been tested negative in a serum pregnancy test within 7 days prior to inclusion.
    8. Written informed consent obtained prior any study-specific procedure.
    E.4Principal exclusion criteria
    10. Women who are lactating.
    35. Patients unwilling to undergo a safety follow-up for 15 years
    11. Foreseeable poor compliance to the study procedures.
    12. Previous treatment with investigational gene or cell therapy medicine products.
    13. Use of other investigational products or other anti-leukaemic therapy within 5 half-lives or within 14 days prior to UCART19 administration, whichever is a shorter duration, participation in non-interventional registries or epidemiological studies is allowed.
    14. CD19 negative B-cell leukaemia.
    16. Burkitt cell (L3 ALL) or mixed lineage acute leukaemia.
    36. Clinically suspected extra-medullary involvement.
    19. Active CNS leukaemia.
    20. Clinically active significant CNS dysfunction.
    37. Previous severe neurological toxicity related to blinatumomab.
    18. Radioimmunotherapy, radiotherapy, within 8 weeks (except prophylaxis of CNS involvement) before Inclusion.
    21. Autologous HSCT within 6 weeks or allogeneic HSCT within 3 months prior Screening.
    22. Use of rituximab and other anti CD 20 antibodies known to have the same epitope as rituximab or anti CD20 for which the epitope is unknown within 6 months prior to Screening.
    23. Presence of donor-specific anti-HLA antibodies.
    24. Active acute or chronic GvHD requiring therapy.
    25. Patient with autoimmune disease treated with immunosuppressive agents, e.g. corticosteroids > 1 mg/kg, within 5 days prior to administration of UCART19. Infliximab must be stopped at least 45 days prior to administration of UCART19.
    26. A known hypersensitivity to any of the test materials or related compounds including murine and bovine products.
    27. Any known uncontrolled cardiovascular disease or any of the following in the previous 6 months before Inclusion: ventricular or atrial dysrhythmia ≥ grade 2, bradycardia ≥ grade 2, myocardial infarction, severe/unstable angina, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, hypertension not adequately controlled by standard medications. In addition, left ventricular ejection fraction (LVEF) < 45% assessed by echocardiography or Multi Gated Acquisition Scan (MUGA) assessed at Screening.
    28. History of hypertension crisis or hypertensive encephalopathy within 3 months prior to Screening.
    29. Active bacterial, fungal, protozoal or viral infection not controlled by adequate treatment, at Inclusion, and presence of positive blood cultures within 7 days before Inclusion
    30. Any major surgery within 3 months prior to Screening.
    31. Abnormal findings during the Screening period, any other medical condition(s) or laboratory findings that, in the opinion of the investigator, might jeopardize the patient’s safety.
    32. Any planned medical/surgical treatment that might interfere with the ability to comply with the study requirements.
    33. Evidence of another malignancy within 2 years prior to Screening (except in situ basal or squamous cervix or skin cell carcinoma).
    34. Any mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude.
    38. Patients tested positive for human immunodeficiency virus (HIV) and/or human T-lymphotropic virus (HTLV), at Inclusion
    E.5 End points
    E.5.1Primary end point(s)
    DLT at Day 28 post UCART19 infusion and AE throughout the study
    E.5.1.1Timepoint(s) of evaluation of this end point
    Evaluation of DLTs at Day 28
    E.5.2Secondary end point(s)
    To assess the anti-leukaemic activity with:
    - Response at D28, D84 and overall assessed by morphologic assessment of bone marrow, blood, lymph nodes (if applicable or available)
    - duration of response, time to response, disease-specific survival and progression-free survival.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Throughout the study
    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 Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Analysis of safety and/or efficacy biomarkers
    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. 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 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 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 Yes
    E.8.5.1Number of sites anticipated in the EEA2
    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
    United States
    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
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months9
    E.8.9.1In the Member State concerned days13
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months10
    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 Yes
    F.1.1Number of subjects for this age range: 1
    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) Yes
    F. of subjects for this age range: 1
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 16
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 1
    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 Yes
    F. of other specific vulnerable populations
    minors > = 16 years old
    F.4 Planned number of subjects to be included
    F.4.1In the member state3
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 14
    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)
    After the discontinuation of the study, the participant will access to an appropriate medical care by his doctor.
    After completion of EOS visit/WD, consenting patients will transition to a long term follow-up study (under a separate protocol) and will be followed-up for up to 15 years. The patient’s participation in a long term follow-up study is a requirement of the regulatory authorities in the follow-up of any patient having received a gene therapy treatment.
    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 Decision2017-10-20
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-04-26
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2020-07-28
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