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    Summary
    EudraCT Number:2019-004081-18
    Sponsor's Protocol Code Number:JCAR017-FOL-001
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2020-10-07
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2019-004081-18
    A.3Full title of the trial
    A PHASE 2, OPEN-LABEL, SINGLE-ARM, MULTICOHORT, MULTICENTER TRIAL TO EVALUATE THE EFFICACY AND SAFETY OF JCAR017 IN ADULT SUBJECTS WITH RELAPSED OR REFRACTORY INDOLENT B-CELL NONHODGKIN LYMPHOMA (NHL) (Transcend FL)
    Studio di fase 2, in aperto, a braccio singolo, a coorti multiple, multicentrico per valutare l’efficacia e la sicurezza di JCAR017 in soggetti adulti con linfoma non – Hodgkin a cellule B indolente recidivante o refrattario (NHL) (TRANSCEND FL)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to evaluate the efficacy and safety of JCAR017 in adult subjects with a type of cancer that affects B-cells, a type of white blood cell.
    Studio per valutare l’efficacia e la sicurezza di JCAR017 in soggetti adulti con un tipo di cancro che colpisce le cellule B, un tipo di globuli bianchi.
    A.3.2Name or abbreviated title of the trial where available
    NA
    NA
    A.4.1Sponsor's protocol code numberJCAR017-FOL-001
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04245839
    A.5.3WHO Universal Trial Reference Number (UTRN)U1111-1244-9768
    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 SponsorCELGENE CORPORATION
    B.1.3.4CountryUnited States
    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 supportCelgene Corporation
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCelgene Corporation
    B.5.2Functional name of contact pointClinicalTrialDisclosure
    B.5.3 Address:
    B.5.3.1Street Address86 Morris Avenue
    B.5.3.2Town/ citySummit, New Jersey
    B.5.3.3Post code07901
    B.5.3.4CountryUnited States
    B.5.4Telephone number0019137096862
    B.5.5Fax number0019088974074
    B.5.6E-mailClinicalTrialDisclosure@celgene.com
    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 Yes
    D.2.5.1Orphan drug designation numberEU/3/17/1890, EU/3/18/2018, EU/3/18/2099
    D.3 Description of the IMP
    D.3.1Product nameJCAR017
    D.3.2Product code [JCAR017]
    D.3.4Pharmaceutical form Suspension 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 INNLISOCABTAGENE MARALEUCEL
    D.3.9.2Current sponsor codeJCAR017
    D.3.9.4EV Substance CodeSUB191306
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    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 Yes
    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.IMP: 2
    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.2.1.2Country which granted the Marketing AuthorisationItaly
    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 nameFludarabina
    D.3.2Product code [NA]
    D.3.4Pharmaceutical form Concentrate for solution for 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 INNFLUDARABINA
    D.3.9.1CAS number 21679-14-1
    D.3.9.2Current sponsor codeNA
    D.3.9.4EV Substance CodeSUB07678MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    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) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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 Yes
    D.3.11.13.1Other medicinal product typeAnalogo delle purine
    D.IMP: 3
    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.2.1.2Country which granted the Marketing AuthorisationItaly
    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 nameCiclofosfamide
    D.3.2Product code [NA]
    D.3.4Pharmaceutical form Powder for solution for 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 INNCICLOFOSFAMIDE
    D.3.9.1CAS number 6055-19-2
    D.3.9.2Current sponsor codeNA
    D.3.9.3Other descriptive nameCYCLOPHOSPHAMIDE MONOHYDRATE
    D.3.9.4EV Substance CodeSUB16414MIG
    D.3.10 Strength
    D.3.10.1Concentration unit g gram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    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) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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 Yes
    D.3.11.13.1Other medicinal product typeAgente alchilante
    D.IMP: 4
    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.2.1.2Country which granted the Marketing AuthorisationItaly
    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 nameTocilizumab
    D.3.2Product code [NA]
    D.3.4Pharmaceutical form Concentrate for solution for 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 INNTOCILIZUMAB
    D.3.9.1CAS number 375823-41-9
    D.3.9.2Current sponsor codeNA
    D.3.9.3Other descriptive nameTocilizumab
    D.3.9.4EV Substance CodeSUB20313
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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 Yes
    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 Yes
    D.3.11.13.1Other medicinal product typeAnticorpo monoclonale ricombinante umanizzato
    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
    Relapsed or refractory indolent B-cell Non-Hodgkin Lymphoma (NHL)
    Linfoma non Hodgkin (NHL) a cellule B indolente recidivante o refrattario
    E.1.1.1Medical condition in easily understood language
    A cancer of B-cells, a type of white blood cell responsible for producing antibodies
    Un cancro delle cellule B, un tipo di globuli bianchi responsabili della produzione di anticorpi.
    E.1.1.2Therapeutic area Diseases [C] - Immune System Diseases [C20]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level HLT
    E.1.2Classification code 10016895
    E.1.2Term Follicle centre lymphomas diffuse predominantly small cell
    E.1.2System Organ Class 100000004851
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10076596
    E.1.2Term Marginal zone lymphoma
    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 21.1
    E.1.2Level PT
    E.1.2Classification code 10029460
    E.1.2Term Nodal marginal zone B-cell lymphoma
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    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 efficacy of JCAR017 in subjects with relapsed/refractory (r/r) follicular lymphoma (FL) and marginal zone lymphoma (MZL)
    L’obiettivo primario dello studio è valutare l’efficacia di JCAR017 in soggetti con linfoma follicolare (FL) recidivato/refrattario (r/r) e linfoma della zona marginale (MZL)
    E.2.2Secondary objectives of the trial
    The secondary objectives are:
    -To evaluate other measures of efficacy
    -To evaluate the safety of JCAR017
    -To characterize the pharmacokinetic (PK) profile of JCAR017
    -To evaluate the Health-Related-Quality of Life (HRQoL) using preselected primary domains of interest in the EORTC QLQ-C30 (global
    health/QoL, physical functioning, fatigue, pain) and FACT-LymS (lymphoma specific symptoms)
    Gli obiettivi secondari sono:
    -Valutare altri parametri di efficacia
    -Valutare la sicurezza di JCAR017
    -Caratterizzare il profilo farmacocinetico (PK) di JCAR017
    -Valutare la Qualità della vita correlata alla salute (HRQoL) usando domini primari preselezionati di interesse nel EORTC QLQ-C30 (salute generale/QoL, funzionamento fisico, affaticamento, dolore) e nel FACT-LymS (sintomi specifici del linfoma)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Subject has FL (Grade 1, 2, or 3a) or MZL histologically confirmed within 6 months of screening, as assessed by local pathology.
    2. Subject must have relapsed or refractory disease, as assessed by the invest.
    3. Subject must have measurable disease as follows:
    a. For FL subjects (Cohorts 1, 2, and 3), PET-pos disease with at least one PET-pos lesion and at least one measurable nodal or extranodal lesion greater than 1.5 cm in the long axis (refer to protocol, App F)
    b. MZL subjects (Cohort 4) with PET non-avid disease should have at least one measurable nodal lesion greater than 2.0 cm in the long axis (PET-pos disease is not required for MZL) - refer to protocol, App F
    4. Subject must have received the following, depending on cohort assignment:
    a. Cohort 1 (4L+ r/r FL): received at least 3 prior lines of systemic therapy. At least one of these lines must be a combination which
    included an anti-CD20 antibody (eg, rituximab, obinutuzumab) and an alkylating agent. Prior HSCT is permitted as a prior line of therapy. A group of 4L+ double-refractory subjects will be enrolled in this cohort (refer to protocol section 4.2)
    b. Cohort 2 (3L r/r FL): received 2 prior lines of syst therapy. At least one of these lines must be a combination which included an antiCD20 antibody (eg, rituximab, obinutuzumab) and an alkylating agent
    In addition to this requirement, subjects must meet one of the following high-risk criteria: have relapsed or refractory disease within 12 months of completion of a prior line of therapy and have received prior combination therapies, OR relapsed after HSCT, OR meet the definition of double refractory (refer to protocol section 4.2)
    c. Cohort 3 (2L r/r FL): received 1 prior line of combination systemic therapy, which included an anti-CD20 antibody (eg, rituximab,
    obinutuzumab) and an alkylating agent. A group of POD24 subjects, defined as having progressive disease within 24 months of diagnosis and have received treatment within 6 months of the original FL diagnosis, will be enrolled to this cohort. The 2L subjects that do not meet this POD24 definition must instead meet one of the modified GELF criteria (NCCN, 2019) as outlined in protocol section 4.2, number 5
    d.Cohort 4 (3L+ MZL): received at least 2 prior syst therapies, including at least one line of combination syst therapy, therapy
    with an anti-CD20 antibody (eg, rituximab, obinutuzumab) and an alkylating agent, or relapsed after HSCT. Splenectomy for SMZL is considered as a line of therapy. Antibiotics for extranodal MZL (ENMZL) are not considered as a prior line of
    therapy
    5. Subject is = 18 years of age the time of signing the ICF
    6. Subjects who have received previous CD19-targeted therapy must have CD19-positive lymphoma confirmed on a biopsy since completing the prior CD19-targeted therapy
    7. Subject has ECOG performance status of 0 or 1
    8. Subject has adequate organ function.
    9. Subject has adequate vascular access for leukapheresis procedure.
    10. Subjects must agree to not donate blood, organs, sperm or semen, and egg cells for usage in other individuals for at least 1 year following lymphodepleting chemotherapy.
    11. FCBP subjects must:
    a. Have 2 neg pregnancy tests as verified by the Investigator (one neg serum ß-hCG pregnancy test result at screening, and within 7 days prior to the first dose of lymphodepleting chemotherapy).
    b. Either commit to true abstinence from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with, effective contraception without interruption.
    c. Agree to abstain from breastfeeding during study participation and for at least 12 months following lymphodepleting chemotherapy.
    12 Male subjects must:
    a. Practice true abstinence (which must be reviewed on a monthly basis) or agree to use a condom during sexual contact with a pregnant female or a FCBP for 12 months after lymphodepleting chemotherapy even if he has undergone a successful vasectomy.
    1. Il sogg ha FL (di Grado 1, 2 o 3a) o MZL confermato istologicam entro 6 mesi dallo screening, valutato dal lab locale di patol
    2. Il sogg deve avere una malattia recid o refratt, in base al giudizio dello speriment.
    3. Il sogg deve avere una malattia misurab, definita come:
    a. Per i sogg con FL (Coorti 1, 2 e 3), malattia pos alla PET con almeno una lesione pos alla PET e almeno una lesione nodale o extranodale misurabile magg di 1,5 cm longitud (fare rif al prot, App F)
    b. I sogg con MZL (Coorte 4) con malattia non avida alla PET devono avere almeno una lesione nodale misurab magg di 2,0 cm longitud (per MZL non è necessario avere malattia pos alla PET) - Fare rif al prot, App F)
    4. Il sogg deve aver ricevuto quanto segue, in base all’assegnaz della coorte:
    a. Coorte 1 (4L+ r/r FL): ha ricevuto almeno 3 preced linee di terapia sist. Almeno una deve essere una combinaz che comprend un anticorpo anti-CD20 (es. rituximab, obinutuzumab) e un agente alchil. HSCT preced è concesso come preced linea di terapia. In questa coorte sarà arruolato un gruppo di sogg 4L+ doppiam refratt (fare rif alla sezione 4.2 del prot)
    b. Coorte 2 (3L+ r/r FL): ha ricevuto almeno 2 preced linee di terapia sist. Almeno una deve essere una combinaz che comprend un anticorpo anti-CD20 (es. rituximab, obinutuzumab) e un agente alchil. Oltre a questo requisito, i sogg devono soddisf uno dei seguenti criteri di alto rischio: avere una malattia recid o refratt entro 12 mesi dal completam della preced linea di terapia e aver ricevuto preced terapie combinate, O recid dopo HSCT, O soddisf la definizione di doppio refratt (fare rif alla sezione 4.2 del prot)
    c. Coorte 3 (2L+ r/r FL): ha ricevuto almeno 1 preced linea di terapia sist combinata che includ un anticorpo anti CD20 (es. rituximab, obinutuzumab) e un agente alchil. In questa coorte sarà arruolato un gruppo di sogg POD24, definiti come aventi malattia progress entro 24 mesi dalla diagnosi, e che hanno ricevuto un trattam entro 6 mesi dalla diagnosi iniz di FL. I sogg 2L che non soddisfano questa definiz POD24 devono invece soddisfare uno dei criteri GELF modificati (NCCN, 2019) come delineato nella sezione 4.5 del prot, numero 5
    d. Coorte 4 (3L+ MZL): ha ricevuto almeno 2 preced terapie sist che includ almeno una linea di terapia sist combinata, una terapia con un anticorpo anti CD20 (es. rituximab, obinutuzumab) e un agente alchil, o che sono recid dopo HSCT. La splenectomia per SMZL è considerata una linea di terapia. Gli antibiotici per ENMZL non sono consid una preced linea di terapia
    5. Il sogg ha = 18 anni di età al mom della firma dell’ICF
    6. Sogg che hanno ricevuto una preced linea di terapia mirata a CD19 devono avere un linfoma CD19 pos confermato alla biopsia da quando hanno complet la preced terapia mirata a CD19
    7. Il sogg ha un ECOG di 0 o 1
    8. Il sogg ha una funz organica adeguata.
    9. Il sogg ha un adeguato accesso vascolare per la leucaferesi.
    10. I sogg devono acconsent a non donare sangue, organi, sperma o seme e cellule uovo da usare in altri individui fino ad almeno 1 anno dopo la chemio linfodepletiva.
    11. I sogg FCBP devono:
    a. Avere 2 test di gravid neg verificati dallo Speriment (un test di gravid serico neg alla ß-hCG allo screening e uno entro 7 gg prima della prima dose di chemio linfodepletiva).
    b. Impegnarsi a praticare astinenza compl da contatti eterosess (che deve essere riesaminata su base mens e documentata) o decidere di utilizz contraccez efficace senza interruz e di essere in grado di conformarsi alla stessa.
    c. Convenire di astenersi dall'allattam durante la partecipaz allo studio e per almeno 12 mesi dopo la chemio linfodepletiva.
    12 I sogg di sesso masch devono:
    a. Pratic astinenza compl (che deve essere valutata su base mensile) o acconsentire ad usare un preserv durante il contatto sess con una donna in stato di gravid o potenzialm fertile per 12 mesi dopo la chemio linfodepletiva, anche se il sogg fosse stato sottoposto ad un intervento riuscito di vasect.
    E.4Principal exclusion criteria
    1. Evidence of composite DLBCL and FL, or of transformed FL. Subjects with World Health Organization (WHO) sub-classification of duodenaltype FL
    2. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in
    the study based on investigator's judgement.
    3. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to
    participate in the study based on investigator's judgement.
    4. Any condition that confounds the ability to interpret data from the study based on investigator's judgement.
    5. Central nervous system (CNS)-only involvement by malignancy (note: subjects with secondary CNS involvement are allowed on
    study).
    6. History of another primary malignancy that has not been in remission for at least 2 years For specific exceptions, see protocol section 4.3
    7. Previous treatment with alemtuzumab within 6 months of leukapheresis, or treatment with fludarabine or cladribine within 3 months of leukapheresis.
    8. Prior CAR T-cell or other genetically-modified T-cell therapy.
    9. History of or active human immunodeficiency virus (HIV).
    10. Active hepatitis B or active hepatitis C.
    11. Uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment.
    12. Active autoimmune disease requiring immunosuppressive therapy.
    13. Presence of acute or chronic graft-versus-host disease (GVHD).
    14. History of specific cardiovascular conditions within the past 6 months prior to signing the ICF (see protocol section 4.3).
    15. History or presence of clinically relevant central nervous system (CNS) pathology not related to disease under study. (see protocol
    section 4.3)
    16. Subject is a pregnant or nursing (lactating) woman.
    17. Subject has an intolerance to dimethyl sulfoxide (DMSO) and/or dextran
    18. Progressive vascular tumor invasion, thrombosis, or embolism
    19. Venous thrombosis or embolism not managed on a stable regimen of anticoagulation
    20. Subject has received or undergone the following (See section 4.3 for additional details).
    a. Therapeutic doses of corticosteroids (defined as >20 mg/day prednisone or equivalent) within 7 days prior to unstimulated
    leukapheresis.
    b. Cytotoxic chemotherapeutic agents that are not considered lymphotoxic and intrathecal chemotherapy must be stopped > 7 days prior to unstimulated leukapheresis
    c. Experimental agents within 4 weeks prior to signing the ICF unless no response or PD is documented on the experimental therapy
    d. Ibrutinib, lenalidomide and PI3Ki within 3 half-lives prior to unstimulated leukapheresis
    e. Immunosuppressive therapies within 4 weeks prior to leukapheresis and JCAR017 infusion
    f. Donor lymphocyte infusion (DLI) within 6 weeks prior to JCAR017 infusion
    g. Radiation within 6 weeks of leukapheresis.
    h. Systemic immunostimulatory agents within 6 weeks or 5 half-lives of the drug, whichever is shorter, prior to JCAR017 infusion.
    1. Evidenza di DLBCL e FL composito o di FL trasformato. Soggetti con sottoclassificazione World Health Organization (WHO) di FL di tipo duodenale
    2. In base al giudizio dello sperimentatore il soggetto ha una qualsiasi patologia medica significativa, anomalia di test di laboratorio o malattia psichiatrica che gli impedirebbe di partecipare allo studio.
    3. In base al giudizio dello sperimentatore il soggetto presenta qualsiasi condizione, compresa la presenza di anomalie dei test di laboratorio, che lo esporrebbe a un rischio inaccettabile nel caso in cui partecipasse allo studio.
    4. In base al giudizio dello sperimentatore, il soggetto presenta qualsiasi condizione che confonda la capacità di interpretare i dati provenienti dallo studio.
    5. Neoplasia maligna che coinvolge solo il sistema nervoso centrale (CNS) (nota: i soggetti con coinvolgimento secondario del SNC possono partecipare allo studio).
    6. Anamnesi di altra neoplasia maligna primaria che non sia in remissione da almeno 2 anni. Per eccezioni specifiche vedere la sezione 4.3 del protocollo
    7. Precedente trattamento con alemtuzumab entro 6 mesi dalla leucaferesi o trattamento con fludarabina o cladribina entro 3 mesi dalla leucaferesi.
    8. Precedente terapia cellulare CAR T o con cellule T geneticamente modificate.
    9. Anamnesi o presenza di virus attivo dell’immunodeficienza umana (HIV).
    10. Virus attivo dell’epatite B o C.
    11. Infezione sistemica non controllata fungina, batterica, virale o di altro tipo (compresa la tubercolosi) nonostante antibiotici appropriati o altro trattamento.
    12. Malattia autoimmune attiva che richieda terapia immunosoppressiva.
    13. Malattia del trapianto contro l’ospite (GvHD) acuta o cronica.
    14. Anamnesi di malattie cardiovascolari specifiche negli ultimi 6 mesi prima di firmare l’ICF (vedere sezione 4.3 del protocollo).
    15. Anamnesi o presenza di patologia clinicamente pertinente del sistema nervoso centrale (SNC) non correlata alla malattia in studio (vedere sezione 4.3 del protocollo).
    16. Il soggetto è una donna in stato di gravidanza o che allatta con latte materno.
    17. Il soggetto ha un’intolleranza al dimetilsolfossido (DMSO) e/o al destrano
    18. Invasione vascolare progressiva del tumore, trombosi o embolia
    19. Trombosi venosa o embolia non trattata da un regime stabile di anticoagulanti
    20. Il soggetto ha ricevuto o è stato sottoposto ad uno dei seguenti agenti (Vedere sezione 4.3 per ulteriori dettagli).
    a. Dosi terapeutiche di corticosteroidi (definiti con >20 mg/die di prednisone o equivalente) entro 7 giorni prima della leucaferesi non stimolata.
    b. Gli genti chemioterapici citotossici che non sono considerati linfotossici e la chemioterapia intratecale devono essere interrotti > 7 giorni prima della leucaferesi non stimolata
    c. Agenti sperimentali entro 4 settimane prima di firmare l’ICF salvo che sia documentata nessuna risposta o PD alla terapia sperimentale
    d. Ibrutinib, lenalidomide e PI3Ki entro 3 emivite prima della leucaferesi non stimolata
    e. Terapie immunosoppressive entro 4 settimane prima della leucaferesi e dell’infusione di JCAR017
    f. Infusione di linfociti da donatore (DLI) entro 6 settimane prima dell’infusione di JCAR017
    g. Radiazione entro 6 settimane dalla leucaferesi.
    h. Agenti immunostimolatori sistemici entro 6 settimane o 5 emivite del farmaco, in base al periodo più breve, prima dell’infusione di JCAR017.
    E.5 End points
    E.5.1Primary end point(s)
    Complete response rate (CRR) as assessed by PET-CT (FL) or CT (MZL) using "The Lugano Classification".
    Tasso di risposta completa (CRR) valutato mediante TC-PET (FL) o TC (MZL) usando la “Classificazione Lugano".
    E.5.1.1Timepoint(s) of evaluation of this end point
    Up to 24 months
    Fino a 24 mesi
    E.5.2Secondary end point(s)
    -Overall response rate (ORR) as assessed by PET-CT (FL) or CT (MZL) using "The Lugano Classification".
    -Duration of response (DOR) if Best Overall Response (BOR) is CR, as assessed by PET-CT and/or CT using "The Lugano Classification".
    -Duration of response (DOR) as assessed by PET-CT and/or CT using "The Lugano Classification".
    -Progression-free survival (PFS) as assessed by PET-CT and/or CT using "The Lugano Classification".
    -Overall Survival (OS)
    -Safety
    -Pharmacokinetics (PK)
    -Health-related quality of life (HRQoL)
    -Tasso di risposta complessiva (ORR) valutato mediante TC-PET (FL) o TC (MZL) usando la “Classificazione Lugano".
    -Durata della risposta (DOR) se la Miglior risposta totale (BOR) è CR, valutata mediante TC-PET e/o TC usando la “Classificazione Lugano".
    -Durata della risposta (DOR) valutata mediante TC-PET e/o TC usando la “Classificazione Lugano".
    -Sopravvivenza libera da progressione (PFS) valutata mediante TC-PET e/o TC usando la “Classificazione Lugano".
    -Sopravvivenza totale (OS)
    -Sicurezza
    -Farmacocinetica (PK)
    -Qualità della vita correlata alla salute (HRQoL)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Up to 24 months for all secondary endpoints.
    Fino a 24 mesi per tutti gli endpoint secondari.
    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 Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic Yes
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Potential predictive biomarkers
    Potenziali biomarcatori predittivi
    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 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.8.2.4Number 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 concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA14
    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 Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Austria
    Canada
    France
    Germany
    Italy
    Japan
    Spain
    Sweden
    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
    The End of Trial is defined as either the date of the last visit of the last subject to complete the post-treatment follow-up, the date when the last subject enters the LTFU study, or the date of receipt of the last data point from the last subject that is required for primary, secondary, and/or exploratory analysis, as prespecified in the protocol, whichever is the later date.
    La fine dello studio è definita come la data dell’ultima visita dell’ultimo soggetto che completa il follow-up post-trattamento, la data in cui l'ultimo soggetto accede allo studio di LTFU, oppure la data di ricezione dell’ultimo punto dati dall’ultimo soggetto, necessario per l’analisi primaria, secondaria e/o esplorativa, come specificato a priori nel protocollo (l'ultima tra le date suddette).
    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 months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months6
    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: 75
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 75
    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 60
    F.4.2.2In the whole clinical trial 150
    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)
    Because this protocol involves gene transfer, long-term follow-up for lentiviral vector safety, disease status, and survival will continue on
    this protocol until 24 months after last infusion of JCAR017, regardless of disease status, and rolled over to a separate LTFU protocol
    thereafter for up to 15 years after JCAR017 infusion.
    Poiché questo protocollo comporta il trasferimento genico, il follow-up a lungo termine di sicurezza del vettore lentivirale, dello stato della malattia e della sopravvivenza continuerà in questo protocollo fino a 24 mesi dopo l’ultima infusione di JCAR017, indipendentemente dallo stato della malattia e sarà successivamente trasferito ad un protocollo LTFU separato per un massimo di 15 anni dopo l’infusione di JCAR017.
    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 Decision2020-08-04
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-04-27
    P. End of Trial
    P.End of Trial StatusOngoing
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