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   43925   clinical trials with a EudraCT protocol, of which   7306   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:2012-003967-23
    Sponsor's Protocol Code Number:PCYC-1115-CA
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2013-03-08
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2012-003967-23
    A.3Full title of the trial
    A Randomized, Multicenter, Open-label, Phase 3 Study of the
    Bruton’s Tyrosine Kinase Inhibitor PCI-32765 versus
    Chlorambucil in Patients 65 Years or Older with Treatment-naive
    Chronic Lymphocytic Leukemia or Small Lymphocytic
    Lymphoma
    Studio randomizzato, multicentrico, in aperto,
    di fase 3 per valutare lo inibitore della tirosinchinasi di Bruton PCI-32765 verso
    clorambucile in pazienti treatment-naive di 65 o piu' anni con leucemia linfatica cronica o
    linfoma linfocitico a piccole cellule.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Randomized, Multicenter, Open-label, Phase 3 Study of the
    Bruton’s Tyrosine Kinase Inhibitor PCI-32765 versus
    Chlorambucil in Patients 65 Years or Older with Treatmentnaive
    Chronic Lymphocytic Leukemia or Small Lymphocytic
    Lymphoma
    Studio randomizzato, multicentrico, in aperto, di fase 3 per
    valutare l’inibitore della tirosinchinasi di Bruton PCI-32765 verso
    clorambucile in pazienti treatment-naive di 65 o più anni con leucemia
    linfatica cronica o linfoma linfocitico a piccole cellule.
    A.3.2Name or abbreviated title of the trial where available
    NA
    ND
    A.4.1Sponsor's protocol code numberPCYC-1115-CA
    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 SponsorPharmacyclics, Incorporated
    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 supportPharmacyclics, Incorporated
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationPharmacyclics, Incorporated
    B.5.2Functional name of contact pointMedical Monitor
    B.5.3 Address:
    B.5.3.1Street Address995 East Arques Avenue
    B.5.3.2Town/ citySunnyvale, CA
    B.5.3.3Post code94085-4521
    B.5.3.4CountryUnited States
    B.5.4Telephone number0014082153027
    B.5.5Fax number---
    B.5.6E-mailachu@pcyc.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 numberEMA/OD/156/11
    D.3 Description of the IMP
    D.3.1Product nameIbrutinib
    D.3.2Product code PCI-32765
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNIbrutinib
    D.3.9.1CAS number 936563-96-1
    D.3.9.2Current sponsor codePCI-32765
    D.3.9.3Other descriptive nameIBRUTINIB
    D.3.9.4EV Substance CodeSUB88115
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number140
    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 No
    D.3.11.3.2Gene therapy medical product No
    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.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    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 Leukeran (Chlorambucil)
    D.2.1.1.2Name of the Marketing Authorisation holderAspen Pharma Trading Limited
    D.2.1.2Country which granted the Marketing AuthorisationIreland
    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 nameChlorambucil
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCHLORAMBUCIL
    D.3.9.1CAS number 305-03-3
    D.3.9.4EV Substance CodeSUB06172MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/kg milligram(s)/kilogram
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2
    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 No
    D.3.11.3.2Gene therapy medical product No
    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
    Treatment-naive Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
    Studio in pazienti treatment-naive con
    leucemia linfatica cronica o linfoma linfocitico a piccole cellule
    E.1.1.1Medical condition in easily understood language
    Leukemia or Lymphoma
    Leucemia o linfoma
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 15.1
    E.1.2Level LLT
    E.1.2Classification code 10060669
    E.1.2Term B-cell chronic lymphocytic leukemia/prolymphocytic leukemia/small lymphocytic lymphoma
    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 of PCI-32765 compared with chlorambucil
    based on the Independent Review Committee (IRC) assessment of
    progression-free survival (PFS) in patients 65 years of age or older
    with treatment-naive chronic lymphocytic leukemia (CLL) or small
    lymphocytic lymphoma (SLL)
    Valutare l'efficacia di PCI-32765 rispetto al clorambucile sulla
    base della valutazione del Comitato di revisione indipendente (IRC, independent review
    committee) della sopravvivenza libera da progressione (PFS) in pazienti di 65 anni o più
    affetti da leucemia linfatica cronica naive al trattamento (CLL) o linfoma linfocitico a piccole
    cellule (SLL).
    E.2.2Secondary objectives of the trial
    To compare the treatment groups in terms of the following:
    Efficacy
    • Overall response rate (ORR) according to International Workshop
    on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria, as assessed by the IRC
    • Rate of minimal residual disease (MRD)-negative complete responses (CRs)
    • Overall survival (OS)
    • Fatigue measured by Functional Assessment of Chronic Illness
    Therapy-Fatigue (FACIT-F)
    • Hematological improvement measured by hemoglobin and platelet
    counts

    Safety
    • To evaluate the safety and tolerability of PCI-32765 compared with chlorambucil
    Confrontare i gruppi di trattamento in termini di: Efficacia •
    Tasso di risposta globale (ORR) secondo i criteri del gruppo di lavoro internazionale sulla
    leucemia linaftica cronica (International Workshop on Chronic Lymphocytic Leukemia -
    IWCLL) del 2008, come valutati dall'IRC • Tasso di malattia minima residua
    (MRD)-risposte complete negative (CR) • Sopravvivenza globale (OS) • Affaticamento
    misurato in base al punteggio di Valutazione funzionale della terapia per patologie croniche
    – Affaticamento (FACIT-Fatigue) • Miglioramento ematologico misurato in base
    all'emoglobina e alle conte piastriniche Sicurezza • Valutare la sicurezza e la tollerabilità di
    PCI-32765 rispetto al clorambucile
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Males or females of 65 years of age or greater. Patients between
    the ages of 65 and 70 years of age must have 1 or more of the following comorbidities that may preclude the use of frontline chemo-immunotherapy with fludarabine, cyclophosphamide or rituximab:
    • Creatinine clearance < 70 mL/min using the Cockcroft-Gault equation
    • Platelet count < 100,000/μLor hemoglobin < 10 g/dL
    • Clinically apparent autoimmune cytopenia (autoimmune hemolytic
    anemia or immune thrombocytopenia): Autoimmune hemolytic anemia is defined by at least one marker of hemolysis indirect bilirubin above the upper limit of normal (ULN) not due to liver disease, increased lactate dehydrogenase (above ULN) without alternative etiology, or increased absolute reticulocytosis (above ULN) or bone marrow erythropoiesis in the absence of bleeding) AND at least one marker of direct or indirect autoimmune mechanism (positive direct antiglobulin for IgG or C3d, cold agglutinins) (Ding 2007).; Immune thrombocytopenia is defined by
    platelets ≤ 100,000/μL and increased megakaryocytes on the bone
    marrow exam.
    • Eastern Cooperative Oncology Group (ECOG) performance score = 1 or 2
    2. Diagnosis of CLL/SLL that meets published diagnostic criteria (Hallek 2008):
    • Monoclonal B cells (either kappa or lambda light chain restricted) that are clonally coexpressing at least 1 B-cell marker (CD19 or CD20) and CD5.
    • Prolymphocytes may comprise no more than 55% of blood lymphocytes.
    3. Active disease meeting at least 1 of the following IWCLL criteria (Hallek 2008) for requiring treatment:
    • Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (hemoglobin < 10 g/dL) and/or thrombocytopenia (platelets < 100,000/μL)
    • Massive (≥ 6 cm below the left costal margin), progressive, or symptomatic splenomegaly
    • Massive nodes (at least 10 cm longest diameter), or progressive or symptomatic lymphadenopathy
    • Progressive lymphocytosis with an increase of more than 50%over a 2-month period or a lymphocyte doubling time (LDT) of < 6 months. LDT may be obtained by linear regression extrapolation of absolute lymphocyte counts obtained at intervals of 2 weeks over an observation period of 2 to 3 months. In patients with initial blood lymphocyte counts of < 30,000/μL, LDT should not be used as a single parameter to define indication for treatment. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (eg, infections) should be excluded.
    • Autoimmune hemolytic anemia and/or immune thrombocytopenia
    (defined in Inclusion Criterion 1) that is poorly responsive to corticosteroids or other standard therapy (but see Exclusion Criterion 4).
    • Constitutional symptoms, defined as one or more of the following disease-related symptoms or signs, documented in the patient’s record prior to randomization:
    − unintentional weight loss > 10% within 6 months prior to screening
    − significant fatigue (inability to work or perform usual activities)
    − fevers > 100.5°F or 38.0°C for 2 or more weeks prior to screening without evidence of infection
    − night sweats for more than 1 month prior to screening without evidence of infection
    4. Measurable nodal disease by computed tomography (CT), defined as at least 1 lymph node > 1.5 cm in the longest diameter in a site that has not been previously irradiated. An irradiated lesion may be assessed for measurable disease only if there has been documented progression in that lesion since radiotherapy has ended.
    5. ECOG performance status of 0–2.
    6. Life expectancy > 4 months from randomization.
    7. Adequate hematologic function, defined as absolute neutrophil count (ANC) ≥ 1,000/μL (independent of growth factor support for at least 7 days prior to screening) and platelet count ≥ 50,000/μL (independent of transfusion and growth factor support for at least 7 days prior to screening).
    8. Adequate hepatic function, defined as serum aspartate transaminase (AST) and alanine transaminase (ALT) < 2.5 x ULN, and total bilirubin ≤ 1.5 x ULN.
    9. Adequate renal function, defined as estimated creatinine clearance ≥ 30 mL/min using the Cockcroft-Gault equation.
    10. Willingness to receive all outpatient treatment, all laboratory monitoring, and all radiological evaluations at the institution that administers study drug for the entire study.
    11. Willingness of male patients, if sexually active with a female of childbearing potential, to use an effective barrier method of contraception during the study and for 3 months following the last
    dose of study drug.
    12. Ability to provide written informed consent and to understand and comply with the requirements of the study.
    1. Uomini o donne di età pari o superiore a 65 anni. I pazienti di età compresa tra i 65 e i 70
    anni devono essere affetti da una o più delle seguenti comorbidità che possono precludere
    l'uso di chemio-immunoterapia in prima linea a base di fludarabina, ciclofosfamide o
    rituximab: o Clearance della creatinina < 70 ml/min calcolata in base alla formula di
    Cockroft-Gault o Conta piastrinica < 100,000/L o emoglobina < 10 g/dL o Citopenia
    autoimmune constatabile a livello clinico (anemia emolitica autoimmune o trombocitopenia
    immune) o Punteggio di performance ECOG pari a 1 o 2. 2. Diagnosi di CLL/SLL che
    soddisfa i criteri diagnostici IWCLL (Hallek 2008) 3. Patologia attiva che soddisfa almeno 1
    dei seguenti criteri IWCLL (Hallek 2008) per la richiesta di trattamento: o Evidenza di
    insufficienza di midollo osseo progressiva manifestata dallo sviluppo o dal peggioramento di
    anemia e/o trombocitopenia o Splenomegalia massiccia, progressiva o sintomatica o Nodi
    massivi o linfoadenopatia progressiva o sintomatica o Linfocitosi progressiva o Anemia
    emolitica autoimmune e/o trombocitopenia immune che risponde scarsamente ai
    corticosteroidi o alla terapia standard o Sintomi costituzionali 4. Malattia nodale misurabile
    con tomografia computerizzata (TC) 5. Stato di performance ECOG di 0-2 6. Aspettativa di
    vita > 4 mesi dalla randomizzazione 7. Funzione ematologica adeguata, definita come conta
    assoluta dei neutrofili (ANC) 1,000/L (indipendente dal supporto del fattore di crescita per
    almeno 7 giorni prima dello screening) e conta piastrinica 50,000/L (indipendente dalla
    trasfusione e dal supporto del fattore di crescita per almeno 7 giorni prima dello screening)
    8. Funzione epatica adeguata, definita come aspartato transaminasi (AST) e
    alanino-transaminasi (ALT) nel siero < 2.5 x limite superiore rispetto al normale (ULN) e
    bilirubina totale 1.5 x ULN 9. Funzione renale adeguata, definita come clearance della
    creatinina calcolata 30 ml/min secondo la formula di Cockroft e Gault 10. Intenzione di
    ricevere tutto il trattamento ambulatoriale, tutti i controlli di laboratorio e gli esami
    radiologici presso l'istituto che si occupa della somministrazione del farmaco per l'intera
    durata dello studio 11. Per i pazienti di sesso maschile con una partner in età fertile,
    intenzione di utilizzare un metodo contraccettivo a barriera efficace durante la durata dello studio e per i 3 mesi successivi alla somministrazione dell'ultima dose del farmaco dello
    studio 12. Capacità di fornire un consenso informato scritto e capire, e conformarsi ai
    requisiti dello studio Fare riferimento alla sezione 4 del protocollo per l'elenco completo e
    dettagliato dei criteri di inclusione/esclusione.
    E.4Principal exclusion criteria
    1. Known involvement of the central nervous system by lymphoma
    or leukemia.
    2. History or current evidence of Richter’s transformation or prolymphocytic leukemia.
    3. Documentation of deletion of the short arm of chromosome17: del (17p13.1), as defined by del 17p in more than 20% of cells examined on any pretreatment fluorescence in situ hybridization (FISH) or cytogenetic evaluation.
    4. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura, such as those patients with a declining
    hemoglobin level or platelet count secondary to autoimmune destruction within the 4 weeks prior to first dose of study drug, or the need for daily prednisone ≥ 20 mg daily (or corticosteroid equivalent) to control the autoimmune disease.
    5. Any previous treatment (chemotherapy, radiotherapy, and/or monoclonal antibodies) intended specifically to treat CLL/SLL.
    6. Received any immunotherapy, vaccine, or investigational drug within 4 weeks prior to randomization.
    7. Corticosteroid use within 1 week prior to first dose of study drug, with the exception of inhaled steroid for asthma, topical steroid use, or other local corticosteroid administration.
    Patients requiring systemic steroids at daily doses >20 mg prednisone (or corticosteroid equivalent), or those who are administered steroids for leukemia control or white blood cell(WBC)-count-lowering are excluded.
    8. Major surgery within 4 weeks prior to randomization
    9. History of prior malignancy, with the exception of the following:
    • Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years prior to screening and felt to be at low risk for recurrence by treating physician.
    • Adequately treated nonmelanomatous skin cancer or lentigo maligna melanoma without current evidence of disease.
    • Adequately treated cervical carcinoma in situ without current evidence of disease.
    10. Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York HeartAssociation Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to randomization.
    11. Inability to swallow capsules or tablets, or disease significantly affecting gastrointestinal function and/or inhibiting small intestine absorption (including malabsorption syndrome, resection of the small bowel, or poorly controlled inflammatory bowel disease).
    12. Uncontrolled active systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection, and without improvement despite appropriate antibiotics or other treatment), or requirement for intravenous (IV) antibiotics.
    13. Known history of infection with human immunodeficiency virus (HIV).
    14. Serologic status reflecting active hepatitis B or C infection. Patients who are positive for hepatitis B core antibody and negative for hepatitis B surface antigen must have a negative
    polymerase chain reaction (PCR) result before enrollment. Those who are hepatitis B surface antigen positive or PCR positive will be excluded.
    15. History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
    16. Current life-threatening illness, medical condition, or organ-system dysfunction that, in the investigator’s opinion, could compromise the patient’s safety or put the study at risk.
    17. Requirement for anticoagulation with warfarin.
    18. Requirement for treatment with a strong CYP3A4/5 and/or CYP2D6 inhibitor.
    1. Coinvolgimento noto del sistema nervoso centrale nel linfoma o nella leucemia 2.
    Anamnesi o evidenza attuale di trasformazione Richter o leucemia prolinfocitica 3.
    Documentazione della delezione del braccio corto del cromosoma 17: del(17p13.1) in più del
    20% delle cellule esaminate in occasione di qualsivoglia ibridazione fluorescente in situ
    pre-trattamento (FISH) o valutazione citogenetica 4. Anemia emolitica autoimmune non
    controllata o porpora trombocitopenica idiopatica 5. Qualsiasi trattamento precedente
    (chemioterapia, radioterapia e/o anticorpi monoclonali) indirizzato specificamente al
    trattamento della CLL/SLL 6. Trattamento con immunoterapia, vaccino o agente
    sperimentale nelle 4 settimane precedenti alla randomizzazione 7. Uso di corticosteroidi
    entro 1 settimana antecedente alla somministrazione della prima dose del farmaco dello
    studio, con l'eccezione di somministrazioni per inalazione, uso topico o locale di altra natura.
    Sono esclusi i pazienti che necessitano di steroidi sistemici in dosaggi quotidiani > 20 mg,
    prednisone (o equivalente corticosteroide, si veda l’Appendice N) o quelli a cui sono
    somministrati steroidi per il controllo della leucemia o per ridurre la conta dei globuli
    bianchi. 8. Intervento chirurgico significativo entro 4 settimane prima della randomizzazione.
    9. Storia precedente di tumori maligni, con l'eccezione di quanto segue: o Tumore maligno trattato con intento curativo e senza evidenza di malattia attiva presente per più di 3 anni
    prima dello screening e scarso rischio di recidiva secondo il parere del medico curante o
    Tumore della pelle diverso dal melanoma adeguatamente trattato o melanoma di tipo lentigo
    maligna in assenza di evidenza corrente della malattia o Carcinoma cervicale in situ
    adeguatamente trattato senza evidenza corrente della malattia 10. Malattia cardiovascolare
    attualmente attiva e clinicamente significativa o storia di infarto al miocardio nei 6 mesi
    precedenti la randomizzazione 11. Incapacità di inghiottire capsule o compresse o malattia
    che compromette significativamente la funzionalità gastrointestinale 12. Infezione attiva e
    sistemica di natura micotica, batterica, virale o diversa o necessità di antibiotici
    somministrati per via endovenosa 13. Storia nota di infezione da virus
    dell’immunodeficienza umana (HIV). 14. Stato sierologico che riflette un'infezione da epatite
    B o C attiva 15. Anamnesi di ictus o emorragia intracranica entro 6 mesi prima
    dell'arruolamento 16. Patologia, condizione medica o disfunzione dei sistemi organici
    potenzialmente fatale in corso che potrebbe compromettere la sicurezza del paziente o
    mettere a rischio lo studio 17. Necessità di terapia anticoagulante a base di warfarina 18.
    Necessità di trattamento con un forte inibitore CYP3A4/5 e/o CYP2D6.
    E.5 End points
    E.5.1Primary end point(s)
    PFS as assessed by IRC review according to IWCLL criteria (Hallek 2008) with modification for treatment-related lymphocytosis (Hallek 2012).
    L'endpoint primario di questo studio è la PFS così come valutata dall'IRC ai sensi dei criteri
    IWCLL 2008 (Hallek 2008)con la modifica relativa alla linfocitosi correlata al trattamento
    (Hallek 2012).
    E.5.1.1Timepoint(s) of evaluation of this end point
    (a) after all enrolled patients have received a minimum of 12 months of treatment and/or follow-up, and (b) either 81 confirmed progression or death events have occurred or 15 months have elapsed after the last patient was randomized -whichever comes first.
    L'analisi della PFS verrà eseguita (a) dopo che tutti i pazienti arruolati hanno ricevuto il
    trattamento e/o il follow up per almeno 12 mesi e (b) si sono manifestati 81 eventi di
    progressione o decessi confermati o sono trascorsi 15 mesi dalla randomizzazione dell'ultimo
    paziente - a seconda di quale evento si verifica per primo.
    E.5.2Secondary end point(s)
    Efficacy
    • ORR defined as the proportion of patients who achieve CR, CRi, nPR, or partial response (PR) per IWCLL 2008 criteria over the course of the study as assessed by the IRC
    • Rate of MRD-negative CRs
    • OS
    • Change from baseline FACiT-Fatigue score
    • Rate of hematological improvement in patients with baseline anemia and thrombocytopenia defined by hemoglobin > 11 g/dL or increase ≥ 50% over baseline or platelet count >100,000/mm3, respectively
    Safety
    • Incidence of AEs and changes in laboratory variables, vital signs, and ECG
    In addition, Event-Free Survival (EFS) will be included as a secondary endpoint in response to a European Medicines Agency (EMA) recommendation, where progressive disease (PD), death and non-response at 3 months after randomization are defined as events.
    L'analisi della PFS verrà eseguita (a) dopo che tutti i pazienti arruolati hanno ricevuto il
    trattamento e/o il follow up per almeno 12 mesi e (b) si sono manifestati 81 eventi di
    progressione o decessi confermati o sono trascorsi 15 mesi dalla randomizzazione dell'ultimo
    paziente - a seconda di quale evento si verifica per primo
    E.5.2.1Timepoint(s) of evaluation of this end point
    (a) after all enrolled patients have received a minimum of 12 months of treatment and/or follow-up, and (b) either 81 confirmed progression or death events have occurred or 15 months have elapsed after the last patient was randomized—whichever comes first.
    L'analisi degli end points secondari verrà eseguita (a) dopo che tutti i pazienti arruolati
    hanno ricevuto il trattamento e/o il follow up per almeno 12 mesi e (b) si sono manifestati 81
    eventi di progressione o decessi confermati o sono trascorsi 15 mesi dalla randomizzazione
    dell'ultimo paziente - a seconda di quale evento si verifica per primo.
    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 Yes
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Tolerability
    Tollerabilità
    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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    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) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    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 concerned8
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA46
    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
    Australia
    Canada
    China
    Israel
    New Zealand
    Turkey
    Ukraine
    United States
    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
    The database will be locked at the point that all enrolled patients have had the opportunity to complete at least 12 months of treatment and/or follow-up and either (a) 81 progression or death events have been observed or (b) 15 months have elapsed after the last patient is randomized— whichever occurs first.
    Il database si chiuderà quando tutti i pazienti avranno completato almeno 12 mesi di
    trattamento e/o follow-up e (a) si sono manifestati 81 eventi di progressione o decessi
    confermati o (b) sono trascorsi 15 mesi dalla randomizzazione...
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months9
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years5
    E.8.9.2In all countries concerned by the trial months0
    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) No
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 272
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state35
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 198
    F.4.2.2In the whole clinical trial 272
    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)
    Companion Study PCYC-1116-CA, an extension study for patients with CLL and SLL participating in Study PCYC-1115-CA, will be made available for long-term follow-up and/or second-line therapy for patients who experience IRC-confirmed disease progression, or at the time of PCYC-1115-CA study closure.
    All the other patients be ineligible for Study PCYC-1116-CA and will return to normal standard of care.
    Uno studio di estensione (PCYC-1116-CA) sarà programmato per valutare il follow up a
    lungo termine e/o una terapia di seconda linea per quei pazienti che hanno avuto una
    progressione confermata dall'IRC, ed al momento del termine dello studio PCYC-1115-AC.
    Tuuti i pazienti non eligibili per lo studio di estensione saranno trattati secondo terapia
    standard.
    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 Decision2013-01-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-12-14
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2015-05-04
    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 © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA