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    Summary
    EudraCT Number:2014-001810-24
    Sponsor's Protocol Code Number:BO25323
    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:2015-05-08
    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 number2014-001810-24
    A.3Full title of the trial
    A PROSPECTIVE, OPEN-LABEL, MULTICENTER, RANDOMIZED PHASE III TRIAL TO COMPARE THE EFFICACY AND SAFETY OF A COMBINED REGIMEN OF OBINUTUZUMAB AND GDC-0199 (ABT-199) VERSUS OBINUTUZUMAB AND CHLORAMBUCIL IN PREVIOUSLY UNTREATED PATIENTS WITH CLL AND COEXISTING MEDICAL CONDITIONS
    STUDIO DI FASE III, PROSPETTICO, IN APERTO, MULTICENTRICO, RANDOMIZZATO, TESO A CONFRONTARE L’EFFICACIA E LA SICUREZZA DI UN REGIME COMBINATO DI OBINUTUZUMAB E GDC-0199 RISPETTO A OBINUTUZUMAB E CLORAMBUCILE IN PAZIENTI CON CLL NON TRATTATA IN PRECEDENZA E CONDIZIONI MEDICHE COESISTENTI
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study to Compare the Efficacy and Safety of Obinutuzumab + GDC-0199 versus Obinutuzumab + Chlorambucil in Patients with Chronic Lymphocytic Leukemia
    Uno Studio per confrontare l’efficacia e la sicurezza di obinutuzumab + GDC-0199 rispetto a obinutuzumab + clorambucile in pazienti con leucemia linfatica cronica
    A.3.2Name or abbreviated title of the trial where available
    CLL14
    A.4.1Sponsor's protocol code numberBO25323
    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 SponsorF. Hoffmann-La Roche Ltd
    B.1.3.4CountrySwitzerland
    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 supportF. Hoffmann-La Roche Ltd
    B.4.2CountrySwitzerland
    B.4.1Name of organisation providing supportAbbVie Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationF. Hoffmann-La Roche Ltd
    B.5.2Functional name of contact pointTrial Information Support Line-TISL
    B.5.3 Address:
    B.5.3.1Street AddressGrenzacherstrassen 124
    B.5.3.2Town/ cityBasel
    B.5.3.3Post code4070
    B.5.3.4CountrySwitzerland
    B.5.6E-mailglobal.rochegenentechtrials@roche.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/3/12/1080
    D.3 Description of the IMP
    D.3.1Product nameGDC-0199
    D.3.2Product code RO553-7382/F01-01
    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 INNGDC-0199
    D.3.9.2Current sponsor codeRO5537382
    D.3.9.3Other descriptive nameABT-199
    D.3.9.4EV Substance CodeSUB130380
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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 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/3/12/1080
    D.3 Description of the IMP
    D.3.1Product nameGDC-0199
    D.3.2Product code RO553-7382/F04-01
    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 INNGDC-0199
    D.3.9.2Current sponsor codeRO5537382
    D.3.9.3Other descriptive nameABT-199
    D.3.9.4EV Substance CodeSUB130380
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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: 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 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/3/12/1080
    D.3 Description of the IMP
    D.3.1Product nameGDC-0199
    D.3.2Product code RO553-7382/F05-01
    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 INNGDC-0199
    D.3.9.2Current sponsor codeRO5537382
    D.3.9.3Other descriptive nameABT-199
    D.3.9.4EV Substance CodeSUB130380
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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: 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.2.1.1.1Trade name Gazyvaro
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration Limited, UK
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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/3/12/1054
    D.3 Description of the IMP
    D.3.1Product nameObinutuzumab
    D.3.2Product code RO5072759/F06-01
    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 INNObinutuzumab
    D.3.9.1CAS number 949142-50-1
    D.3.9.2Current sponsor codeRO5072759
    D.3.9.3Other descriptive nameOBINUTUZUMAB, GA101
    D.3.9.4EV Substance CodeSUB32751
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1000
    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 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 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 typeRO5072759 is a humanized and glycoengineered monoclonal antibody (mAB)
    D.IMP: 5
    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 Chlorambucil
    D.2.1.1.2Name of the Marketing Authorisation holderAspen Pharma Trading Limited
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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.3.2Product code RO0059978
    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.3.9.2Current sponsor codeRO0059978
    D.3.9.4EV Substance CodeSUB06172MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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
    chronic lymphocytic leukemia
    Leucemia linfatica cronica
    E.1.1.1Medical condition in easily understood language
    chronic lymphocytic leukemia
    Leucemia linfatica cronica
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.0
    E.1.2Level LLT
    E.1.2Classification code 10008956
    E.1.2Term Chronic lymphatic leukaemia
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To determine efficacy by investigator-assessed PFS of a combined regimen of obinutuzumab and GDC 0199 compared with GClb in previously untreated patients with CLL who have coexisting medical conditions.
    Determinare l’efficacia in base alla PFS valutata dallo sperimentatore di un regime combinato di obinutuzumab + GDC 0199 rispetto a GClb in pazienti affetti da CLL non trattata in precedenza che presentano condizioni mediche coesistenti.
    E.2.2Secondary objectives of the trial
    To determine efficacy as assessed by additional outcome measures, including Independent Review Committee [IRC]-assessed PFS, overall response and MRD response rate as measured by allele-specific oligonucleotide polymerase chain reaction [ASO-PCR]
    Determinare l’efficacia valutata dalle misure aggiuntive degli outcome (specificate nella sezione 3.4.2, che includono la PFS valutata dal Comitato di revisione indipendente (IRC), il tasso di risposta globale e di risposta della MRD, misurati mediante reazione a catena della polimerasi con oligonucleotide allele-specifico (ASO-PCR) (vedere l’obiettivo secondario di sicurezza nella sezione 2.2.)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Documented previously untreated CLL according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria
    - CLL requiring treatment according to IWCLL criteria
    - Total Cumulative Illness Rating Scale (CIRS score) > 6
    - Adequate marrow function independent of growth factor or transfusion support within 2 weeks of screening as per protocol, unless cytopenia is due to marrow involvement of CLL
    - Adequate liver function
    - Life expectancy > 6 months
    - Agreement to use highly effective contraceptive methods per protocol
    CLL non trattata in precedenza, documentata in base ai criteri dell’International Workshop on Chronic Lymphocytic Leukemia (IWCLL)
    - CLL che necessita di trattamento secondo i criteri IWCLL
    - Punteggio totale della scala CIRS >6
    - Funzionalità midollare adeguata indipendentemente dai fattori di crescita o dal supporto della trasfusione nelle 2 settimane precedenti lo screening, tranne qualora la citopenia sia dovuta a interessamento del midollo per CLL
    - Funzionalità epatica adeguata
    - Aspettativa di vita >6 mesi
    - accettare di usare metodi contraccettivi ad alta efficacia come da protocollo
    E.4Principal exclusion criteria
    Transformation of CLL to aggressive Non-Hodgkin's lymphoma (Richters transformation or pro-lymphocytic leukemia)
    - Known central nervous system involvement
    - Patients with a history of confirmed progressive multifocal leukoencephalopathy (PML)
    - An individual organ/ system impairment score of 4 as assessed by the CIRS definition limiting the ability to receive the treatment regimen of this trial with the exception of eyes, ears, nose, throat organ system
    - Patients with uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia
    - Inadequate renal function
    - History of prior malignancy, except for conditions as listed in the protocol if patients have recovered from the acute side effects incurred as a result of previous therapy
    - Patients with active bacterial, viral, or fungal infection requiring systemic treatment within the last two months prior to registration
    - History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
    - Hypersensitivity to chlorambucil, obinutuzumab, or GDC-0199 or to any of the excipients
    - Pregnant women and nursing mothers
    - Positive test results for chronic HBV infection (defined as positive HBsAg serology) or positive test result for hepatitis C (hepatitis C virus [HCV] antibody serology testing)
    - Patients with known infection with human immunodeficiency virus (HIV) or human T-cell leukemia virus-1 (HTLV-1)
    - Requires the use of warfarin, marcumar, or phenprocoumon
    - Received agents known to be strong CYP3A4 inhibitors or inducers within 7 days prior to the first dose of study drug
    Trasformazione di CLL in NHL (sindrome di Richter o leucemia prolinfocitica) in forma aggressiva
    - Interessamento noto del sistema nervoso centrale
    Pazienti con un’anamnesi di leucoencefalopatia multifocale progressiva (PML) confermata
    - Un punteggio di compromissione di un singolo sistema/organo pari a 4 secondo la definizione della scala CIRS, che limita la capacità di ricevere il regime di trattamento di questo studio, con l’eccezione di occhi, orecchie, naso, gola
    - Pazienti con anemia emolitica autoimmune o trombocitopenia autoimmune non controllata
    - Funzione renale inadeguata
    - Anamnesi di precedente malignità, eccetto che per le condizioni elencate di seguito, se i pazienti si sono ripresi dagli effetti collaterali acuti manifestatisi a causa della terapia precedente
    - Pazienti con infezione attiva di natura batterica, virale o fungina che richiede il trattamento sistemico nei 2 mesi precedenti la registrazione

    Anamnesi di gravi reazioni allergiche o anafilattiche agli anticorpi monoclonali murini o umanizzati oppure sensibilità o allergia conclamata a prodotti murini
    - Ipersensibilità a clorambucile, obinutuzumab o GDC-0199 o a qualsiasi eccipiente (ad
    - Donne in gravidanza e che allattano
    - Risultati positivi del test dell’infezione cronica da HBV (definita come sierologia positiva per HBsAg) o risultati positivi del test dell’infezione da epatite C [test sierologico degli anticorpi anti virus dell’epatite C (HCV)]
    - Pazienti con infezione nota causata dal virus dell’immunodeficienza umana (HIV) o dal virus della leucemia a cellule T di tipo 1 dell’uomo (HTLV-1)
    - Condizione che richiede l’uso di warfarin, marcumar o phenprocoumone
    - Trattamento con agenti che sono noti essere forti inibitori o induttori di CYP3A4 nei 7 giorni che precedono la prima dose del farmaco in studio
    E.5 End points
    E.5.1Primary end point(s)
    Progression-free survival (PFS), defined as the time from randomization to the first occurrence of progression, relapse or death from any cause as assessed by the investigator using IWCLL criteria
    PFS, definita come il tempo dalla randomizzazione alla prima comparsa di progressione della malattia, recidiva o decesso per qualsiasi causa, come determinato dallo sperimentatore. La progressione della malattia sarà valutata dallo sperimentatore usando i criteri IWCLL
    E.5.1.1Timepoint(s) of evaluation of this end point
    At baseline, day 1 of cycle 7 and 9, day 1 of cycle 4, day 28 after treatment completion or early termination, during follow up i.e. 3 months after treatment completion or early termination and then regularly until 5 years from last patient enrolled.
    Al basale, al giorno 1 dei cicli 7 e 9, al giorno 1 del ciclo 4, al giorno 28 dopo la fine del trattamento o la “early termination”, durante il follow-up (es.: 3 mesi dopo la fine del trattamento
    E.5.2Secondary end point(s)
    - PFS based on Institutional Review Committee (IRC)-assessments, defined as the time from randomization to the first occurrence of progression or relapse or death from any cause
    - Objective response rate ([ORR] defined as rate of a clinical response of complete response [CR], CR with incomplete bone marrow recovery [CRi] or partial response [PR]) as determined by the investigator, according to the IWCLL criteria
    - Minimal residual disease (MRD) response rate, as measured by allele-specific oligonucleotide polymerase chain reaction (ASO-PCR)
    - ORR at completion of combination treatment response assessment
    - MRD response rate, as measured by ASO-PCR at completion of combination treatment response assessment
    - Overall survival
    - Duration of objective response
    - Best response achieved (CR, CRi, PR, stable disease, or progressive disease)
    - Event-free survival
    - Time to next anti-leukemic treatment
    - Incidence of adverse events assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0
    - Incidence of severe adverse events
    - Incidence of adverse events of special interest
    E.5.2.1Timepoint(s) of evaluation of this end point
    Up to 5 years from last patient enrolled.
    PFS basata sulla valutazione dell’IRC, definita come il tempo dalla randomizzazione alla prima comparsa di progressione della malattia, recidiva o decesso per qualsiasi causa. - ORR (definito come tasso di risposta clinica di CR, CRi o PR) al completamento della valutazione del trattamento, determinato dallo sperimentatore in base alle linee guida IWCLL - Tasso di risposta della MRD, misurato con allele-specific oligonucleotide polymerase chain reaction (ASO-PCR). ORR al completamento della valutazione della risposta al trattamento combinato -
    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 No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic Yes
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Patient reported Outcomes (PRO)
    Patient reported Outcomes (PRO)
    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 concerned10
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA160
    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
    Argentina
    Australia
    Austria
    Brazil
    Bulgaria
    Canada
    Croatia
    Czech Republic
    Denmark
    Egypt
    Estonia
    France
    Germany
    Italy
    Mexico
    New Zealand
    Romania
    Russian Federation
    Slovakia
    Spain
    Switzerland
    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 this study is defined as 5 years from last patient enrolled (unless all patients have died).
    La fine dello studio è definita come 5 anni dall’ultimo paziente arruolato (tranne nel caso in cui tutti i pazienti siano deceduti).
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    E.8.9.1In the Member State concerned months8
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years6
    E.8.9.2In all countries concerned by the trial months8
    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: 357
    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 state150
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 350
    F.4.2.2In the whole clinical trial 432
    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)
    Since survival is an endpoint - the patient will only complete the trial once survival has been reported or the end of study reached. At that time patients will be followed according to standard of care at each site.
    Poichè l’obiettivo è la sopravvivenza, I pazienti completeranno lo studio fino a quando verrà documentata la sopravvivenza o fino al raggiungimento della fine dello studio.
    A quel punto i pazienti verranno seguiti in ciascun centro in accordo allo “standard of care”.

    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation German CLL study group, Cologne University Hospital, Department Internal Medicine I
    G.4.3.4Network Country Germany
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2015-01-21
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-12-17
    P. End of Trial
    P.End of Trial StatusOngoing
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