Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44309   clinical trials with a EudraCT protocol, of which   7356   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).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2022-001101-52
    Sponsor's Protocol Code Number:CART19-BE-03Ped
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2022-08-03
    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 ConcernedSpain - AEMPS
    A.2EudraCT number2022-001101-52
    A.3Full title of the trial
    Phase 2 study of the infusion of autologous, differentiated, peripheral blood T-cells expanded and transduced with a lentivirus to express a chimeric antigen receptor with anti-CD19 specificity (A3B1) coupled with 4-1BB and CD3z co-stimulatory regions (ARI-0001 cells) in children and adolescents (from 0 to 18 years) with CD19+ acute lymphoblastic leukaemia resistant or refractory to treatment
    Estudio de fase 2 de la infusión de células T autólogas, diferenciadas y de sangre periférica expandidas y transducidas con un lentivirus para expresar un receptor de antígeno quimérico con especificidad anti-CD19 (A3B1) junto con regiones coestimuladoras 4-1BB y CD3z (ARI- 0001 células) en niños y adolescentes (de 0 a 18 años) con leucemia linfoblástica aguda CD19+ resistente o refractaria al tratamiento
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Phase 2 study of the infusion of ARI-0001 cells in children and adolescents with CD19+ acute lymphoid leukemia resistant or refractory to treatment
    Estudio fase 2 de la infusión de células aRI-0001 en niños y adolescentes con leucemia linfoblástica aguda CD19+ resistente o refractaria a tratamiento
    A.4.1Sponsor's protocol code numberCART19-BE-03Ped
    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 SponsorFundació Privada per a la Recerca i la Docència Sant Joan de Déu
    B.1.3.4CountrySpain
    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 supportISCIII
    B.4.2CountrySpain
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationFundació Privada per a la Recerca i la docència sant joan de deu
    B.5.2Functional name of contact pointMontserrat Sola
    B.5.3 Address:
    B.5.3.1Street Addresspasseig sant joan de deu 2
    B.5.3.2Town/ cityEsplugues de llobregat
    B.5.3.3Post code08950
    B.5.3.4CountrySpain
    B.5.4Telephone number0034936009751
    B.5.6E-mailmontserrat.sola@sjd.es
    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 ARI-0001
    D.2.1.1.2Name of the Marketing Authorisation holderHospital Clinic de Barcelona
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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 nameARI-0001
    D.3.4Pharmaceutical form Solution for 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 INNVarnimcabtagene autoleucel
    D.3.9.3Other descriptive nameARI-0001
    D.3.9.4EV Substance CodeSUB241411
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number100000 to 3000000
    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
    CD19+ acute lymphoid leukemia resistant or refractory to treatment
    Leucemia linfoblástica aguda resistente o refractaria
    E.1.1.1Medical condition in easily understood language
    acute lymphoid leukemia resistant or refractory to treatment
    Leucemia linfoblástica aguda resistente o refractaria
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10060555
    E.1.2Term Acute lymphoid leukemia
    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 efficacy (response rate) of ARI-0001 cells in paediatric patients with CD19+ acute lymphoblastic leukaemia that is resistant or refractory to therapy.
    Evaluar la eficacia (tasa de respuesta) de las células ARI-0001 en pacientes pediátricos con leucemia linfoblástica aguda CD19+ resistente o refractaria a la terapia.
    E.2.2Secondary objectives of the trial
    • To evaluate safety and tolerability of ARI-0001 therapy
    • To further evaluate efficacy by evaluating duration of response and survival (event-free, relapse-free and overall survival) after ARI-0001 cell infusion
    • To evaluate the kinetics of ARI-0001 cells in peripheral blood, bone marrow and cerebrospinal fluid after its administration
    • To evaluate functional CART-cell persistence by evaluating B-cell aplasia in peripheral blood
    • Evaluar la seguridad y la tolerabilidad de la terapia ARI-0001
    • Evaluar la eficacia mediante la evaluación de la duración de la respuesta y la supervivencia (supervivencia libre de eventos, libre de recaídas y supervivencia global) tras la infusión de células ARI-0001
    • Evaluar la cinética de las células ARI-0001 en sangre periférica, médula ósea y líquido cefalorraquídeo tras su administración
    • Evaluar la persistencia de células CART funcionales evaluando la aplasia de células B en sangre periférica
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Age 0 to 18 years
    2. Diagnosis of relapsed /refractory CD19+ ALL defined as at least one of the following criteria:
    • Primary refractory leukemia to at least 2 lines of therapy
    • First relapse if high-risk features. Definition of high risk 1st relapse will include at least one of the following:
    o any relapse before 6 months after completion of chemotherapy
    o high risk cytogenetics: t(4;11)(q21; q23) /AF4:: KMT2A or t (1;19) (q23; p13) / TCF3/PBX or t(17;19) (q22;p13)/ TCF3::HLF or hypodiploid (<44 chromosomes) or TP53 mutation
    • 2nd or further relapse
    • Any relapse after alloHSCT, provided patient is at least 3 months after the HSCT and 2 weeks off immunosuppressive therapy.
    3. Disease burden defined as:
    • Morphologic relapse in bone marrow (≥5% blasts) or presence of leukemic blasts in an extramedullary site
    • MRD positivity (≥0.01%) by flow cytometry or PCR
    4. Subjects with the following features are NOT excluded:
    • Isolated extramedullary involvement
    • Down syndrome patients
    • CNS3 involvement if disease is stable and a thorough evaluation of risk/benefit assessment has been stablished by the principal investigator and the treating physician
    • Ph+ (BCR::ABL1) ALL if they are intolerant or have failed at least 1 TKI
    • Prior blinatumomab therapy provided blasts remain CD19+ >90% blasts at inclusion
    5. Performance status: Lansky (age <16 years) or Karnofsky (age ≥16 years) ≥ 50%
    6. Life expectancy >3 months
    7. Adequate venous access and no contraindications for lymphoapheresis
    8. Signature of informed consent (patient and/or legal guardian)
    1. Edad 0 a 18 años
    2. Diagnóstico de LLA CD19+ en recaída/refractario definido como al menos uno de los siguientes criterios:
    • Leucemia primaria refractaria a al menos 2 líneas de terapia
    • Primera recaída si presenta características de alto riesgo. La definición de 1ª recaída de alto riesgo incluirá al menos uno de los siguientes:
    o cualquier recaída antes de los 6 meses posteriores a la finalización de la quimioterapia
    o citogenética de alto riesgo: t( 4;11)(q21; q23) /AF4:: KMT2A o t (1;19) (q23; p13) / TCF3/PBX o t(17;19) (q22;p13)/ TCF3 ::HLF o hipodiploide (<44 cromosomas) o mutación TP53
    • Segunda o más recaídas
    • Cualquier recaída después del HSCT alogénico, siempre que el paciente esté al menos 3 meses después del HSCT y 2 semanas sin terapia inmunosupresora.
    3. Carga de enfermedad definida como:
    • Recidiva morfológica en médula ósea ( ≥ 5% de blastos) o presencia extramedular de blastos leucémicos
    • Presencia de enfermedad medible (MRD positiva ( ≥ 0,01%)) por citometría de flujo o PCR
    4. NO se excluyen materias con las siguientes características:
    • Compromiso extramedular aislado
    • Pacientes con sindrome de Down
    • Compromiso del SNC3 si la enfermedad es estable y el investigador principal y el médico tratante han establecido una evaluación exhaustiva de la evaluación de riesgos/beneficios.
    • LLA Ph+ ( BCR:: ABL1) si son intolerantes o han fallado al menos 1 TKI
    • Tratamiento previo con blinatumomab siempre que los blastos sigan siendo CD19+ >90 % de los blastos en el momento de la inclusión
    5. Estado funcional: Lansky (edad <16 años) o Karnofsky (edad ≥16 años) ≥ 50%
    6. Esperanza de vida >3 meses
    7. Acceso venoso adecuado y sin contraindicaciones para la linfoaféresis
    8. Firma de consentimiento informado (paciente y/o tutor legal)
    E.4Principal exclusion criteria
    1) Any other concomitant neoplasia, unless it has been in complete remission for 3 years or longer
    2) Active immunosuppressive therapy with the exception of hydrocortisone 12 mg/m2/day (or equivalent);
    3) Active acute or chronic graft versus host disease (GVHD) >grade 1
    4) Prior therapies:
    • CAR-T cell therapy
    • Donor lymphocytes infusion <28 days before enrollment
    • Immunosuppressive therapy (cyclosporine, mophetil mycophenolate and others) must be stopped <14 days before enrollment
    • Alentuzumab, thymoglobulin (ATG) < 3 months before enrollment

    5) Active infection that is uncontrolled or requiring systemic intravenous medical therapy;
    6) Any experimental or non-commercialized therapy in the previous 4 weeks
    7) Active HIV, HBV or HCV infection
    8) Any concomitant and uncontrolled medical or psychiatric disease that, under investigator consideration, would prevent the subject from participating in the study
    9) Severe organic impairment defined by cardiac ejection fraction <50%, pulmonary reserve defined as > Grade 1 dyspnea and pulse oxygenation <91% on room air, creatinine >1.5 times greater than the upper limit of normality (ULN) for sex and age or conjugated bilirubin >2 x ULN
    10) Lactating or pregnant women
    11) Men or women of childbearing potential unable or unwilling to use highly efficient contraceptive measures during the study.
    1) Cualquier otra neoplasia concomitante, a menos que haya estado en remisión completa durante 3 años o más
    2) Terapia inmunosupresora activa con la excepción de hidrocortisona 12 mg/m2/día (o equivalente);
    3) Enfermedad de injerto contra receptor (EICR) aguda o crónica activa > grado 1
    4) Terapias previas:
    • Terapia de células CAR-T
    • Infusión de linfocitos de donante <28 días antes de la inclusión
    • La terapia inmunosupresora (ciclosporina, micofenolato de mofetilo y otros) debe suspenderse <14 días antes de la inscripción
    • Alentuzumab , timoglobulina (ATG) < 3 meses antes de la inscripción

    5) Infección activa que no está controlada o que requiere tratamiento médico intravenoso sistémico;
    6) Cualquier terapia experimental o no comercializada en las 4 semanas anteriores
    7) activa por VIH, VHB o VHC
    8) Cualquier enfermedad médica o psiquiátrica concomitante y no controlada que, a criterio del investigador, impediría que el sujeto participara en el estudio.
    9) Insuficiencia orgánica grave definida por fracción de eyección cardíaca <50%, reserva pulmonar definida como > grado 1, disnea y oxigenación del pulso <91% con aire ambiente, creatinina >1,5 veces mayor que el límite superior de normalidad (LSN) de acuerdo con la edad y sexo del paciente o bilirrubina conjugada >2 x LSN
    10) Mujeres lactantes o embarazadas
    11) Hombres o mujeres en edad fértil que no pueden o no quieren usar medidas anticonceptivas altamente eficientes durante el estudio.
    E.5 End points
    E.5.1Primary end point(s)
    Complete response rate (complete remission [CR] rate plus CR rate with incomplete haematological recovery [CRi]), with undetectable measurable residual disease by multiparameter flow cytometry within day +100 after the infusion of ARI-0001 cells. In patients with isolated extramedullary disease, response evaluation will be done through morphology and flow cytometry of the cerebrospinal fluid (CSF) and/or imaging tests (PET-CT or MRI)
    • Tasa de respuesta completa (tasa de remisión completa [RC] más tasa de RC con recuperación hematológica incompleta [RCi ]), con enfermedad residual medible indetectable por citometría de flujo multiparamétrica dentro del día +100 después de la infusión de células ARI-0001. En pacientes con enfermedad extramedular aislada, la evaluación de la respuesta se realizará mediante morfología y citometría de flujo del líquido cefalorraquídeo (LCR) y/o pruebas de imagen (PET-TC o RM)
    E.5.1.1Timepoint(s) of evaluation of this end point
    within 100 days after first ARI-0001 infusion
    en los 100 días post primera administracion de ARI-0001
    E.5.2Secondary end point(s)
    1. Event-free survival (EFS) at month 12
    2. Duration of remission
    3. Relapse free survival
    4. Overall survival at 12 months, defined as time between ARI-0001 infusion and death of any cause. Surviving patients will be censored at last follow-up.
    5. Transplant and disease-free survival at 6 and 12 months,
    6. In vivo survival of ARI-0001 cells in peripheral blood as determined by flow cytometry (persistence of B-cell aplasia) monthly in the first 6 months and then at 12 months
    7. B-cell aplasia.
    8. Toxicity, defined as adverse events of grade ≥3 according to common toxicity criteria (version 5.0). Adverse events of significant interest will be CRS, ICANS and cerebral oedema, which will be graded according to the ASTCT classification (Lee et al, 2019). Procedure-related mortality will also be measured.
    1. Supervivencia libre de eventos (EFS) en el mes 12
    2. Duración de la remisión: definida como el tiempo desde el alcance de RC o RCi (lo que ocurra primero) hasta la recaída o muerte por LLA
    3. Supervivencia libre de recaída a los 12 meses
    4. Supervivencia global a los 12 meses
    5. Supervivencia libre de trasplante y de enfermedad a los 6 y 12 meses,
    6. Supervivencia in vivo de células ARI-0001 en sangre periférica determinada por citometría de flujo y por qPCR del transgén semanalmente el primer mes, mensualmente en los primeros 6 meses y luego a los 12 meses.
    7. Aplasia de células B, medida por citometría de flujo, semanalmente el primer mes, mensualmente los primeros 6 meses, cada 3 meses desde el mes 6 hasta el mes 12 y cada 6 meses hasta el final del estudio.
    8. Toxicidad, definida como eventos adversos de grado ≥3 según los criterios comunes de toxicidad (versión 5.0). Los eventos adversos de gran interés serán CRS, ICANS y edema cerebral , que se clasificarán según la clasificación ASTCT (Lee et al, 2019). También se medirá la mortalidad relacionada con el procedimiento.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. At month 12
    2. At month 12, up to 24 months-if applicable
    3. At month 12
    4. At month 6 and 12
    5. At month 6 and 12
    6. At month 6 and 12
    7. D+7,+14,+21,+28,+56,+74+100, month 5,6,9,12,18 and 24
    8. During study up to 24 months-if applicable
    1. Mes 12
    2. Mes 12, hasta mes 24
    3. Mes 12
    4. Mes 6, 12
    5. Mes 6, 12
    6. Mes 6, 12
    7. D+7,+14,+21,+28,+56,+74+100, mes 5,6,9,12,18 y 24
    8. Durante el estudio hasta 24 meses
    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 No
    E.6.5Efficacy No
    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 concerned5
    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 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
    Last patient last visit (LPLV)
    Ultima visita de ultimo paciente
    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 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: 40
    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) Yes
    F.1.1.3.1Number of subjects for this age range: 1
    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: 20
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 15
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) No
    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 state40
    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)
    none
    Ninguno
    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 Decision2022-11-07
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-10-28
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA