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   43873   clinical trials with a EudraCT protocol, of which   7293   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:2015-001767-40
    Sponsor's Protocol Code Number:AZALEA704
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2021-09-10
    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 number2015-001767-40
    A.3Full title of the trial
    A phase II study testing the efficacy of combined azacitidine and lenalidomide for non-M3 acute myeloid leukemia (AML) patients aged between 60 and 70 years, fit, relapsed or refractory: the AZALEA study
    Studio di fase II per testare l'effetto della combinazione azacitidina e lenalidomide in pazienti affetti da leucemia acuta mieloide (LAM) non-M3 di età compresa tra i 60 e 70 anni, fit, recidivati o refrattari: studio AZALEA.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study the effects of azacitidine and lenalidomide combination therapy in patients with acute myeloid leukemia
    Studio degli effetti della combinazione terapeutica azacitidina e lenalidomide in pazienti affetti da leucemia acuta mieloide
    A.3.2Name or abbreviated title of the trial where available
    AZALEA
    AZALEA
    A.4.1Sponsor's protocol code numberAZALEA704
    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 SponsorAZIENDA OSPEDALIERA "OSPEDALI RIUNITI MARCHE NORD"
    B.1.3.4CountryItaly
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportCELGENE INTERNATIONAL SARL
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAZIENDA OSPEDALIERA OSPEDALI RIUNITI MARCHE NORD
    B.5.2Functional name of contact pointEMATOLOGIA E CENTRO TRAPIANTI
    B.5.3 Address:
    B.5.3.1Street AddressVIA LOMBROSO 1
    B.5.3.2Town/ cityPESARO
    B.5.3.3Post code61122
    B.5.3.4CountryItaly
    B.5.4Telephone number0721364022
    B.5.5Fax number0721364052
    B.5.6E-maila.isidori@ospedalimarchenord.it
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name REVLIMID - 25 MG CAPSULA RIGIDA - USO ORALE BLISTER (PCTFE/PVC/ALU) 21 CAPSULE
    D.2.1.1.2Name of the Marketing Authorisation holderCELGENE EUROPE LIMITED
    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 nameLENALIDOMIDE
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    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 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.2.1.1.1Trade name VIDAZA - 25 MG/ML - POLVERE PER SOSPENSIONE INIETTABILE - USO SOTTOCUTANEO - FLACONCINO (VETRO) 100MG 1 FLACONCINO
    D.2.1.1.2Name of the Marketing Authorisation holderCELGENE EUROPE LIMITED
    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 nameAZACITIDINA
    D.3.4Pharmaceutical form Powder for suspension for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    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 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
    ACUTE MYELOID LEUKEMIA
    LEUCEMIA ACUTA MIELOIDE
    E.1.1.1Medical condition in easily understood language
    ACUTE MYELOID LEUKEMIA
    LEUCEMIA ACUTA MIELOIDE
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10024289
    E.1.2Term Leukaemia acute
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Determine the efficacy of combined azacitidine and lenalidomide for non-M3 acute myeloid leukemia (AML) patients aged = 60 and =70 years.
    Determinare l’effetto della combinazione di azacitidina e lenalidomide in pazienti affetti da leucemia acuta mieloide (LAM) non-M3 di età = 60 e = 70 anni.
    E.2.2Secondary objectives of the trial
    Determine the frequency and severity of toxic effects of this regimen in these patients.To define cellular factors associated with clinical response to combined azacitidine and lenalidomide and determine the mechanisms underlying the synergistic effect between azacitidine and lenalidomide on ex vivo model and GEP analysis.
    To investigate the survival parameters of patients on this study
    Determinare la frequenza e la severità degli effetti collaterali di questo regime in questo setting di pazienti;Definire i marcatori cellulari associati alla risposta clinica alla terapia di combinazione con azacitidina e lenalidomide e determinare i meccanismi dell’effetto sinergico di azacitidina e lenalidomide in modelli ex vivo e tramite analisi di espressione genica.Valutare i parametri relativi alla sopravvivenza.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives

    Pharmacogenomics
    Version: 1.0
    Date: 15/12/2015
    Title: Analysis of genomic/genotype charcateristics of patients included in AZALEA protocol and relationship with clinical response
    Objectives: To study the associations between genetic and acquired abnormalities in malignant cells and the response to treatment in acute myeloid leukemia

    Farmacogenomica
    Versione: 1.0
    Data: 15/12/2015
    Titolo: Analisi delle caratteristiche genomiche/genotipiche dei pazienti inseriti nel protocollo AZALEA e relazione con la risposta clinica
    Obiettivi: Studiare le associazioni fra fattori genetici ed le alterazioni acquisite nelle cellule maligne e la risposta al trattamento nelle leucemia acuta mieloide
    E.3Principal inclusion criteria
    •Diagnosis of relapsed AML. A prior CR duration of at least 2 months is required to met the definition of relapsed AML. Patients must have not received more than 1 re-induction course prior to enter the study.
    •Diagnosis of resistant AML. Patients must have received, at the upmost, 2 courses of therapy (first induction and first salvage course) before entering the study, in order to be eligible for enrolment.
    •Patients relapsing after stem cell transplantation, both autologous and allogeneic, are eligible.
    •HIV negativity.
    •Male and female patients aged = 60 and = 70 years.
    •Signed informed consent
    •Morphologically confirmed diagnosis of non-M3 acute myeloid leukemia (AML) in first or subsequent relapse by bone marrow aspiration
    •WBC count = 30,000/mm³. A pretreatment with single dose vinblastine in order to reduce the white blood cell count is allowed within 7 days from the start of therapy. Cytoreduction with hydroxyurea is not allowed.
    •Patient must be not eligible for or not interested in conventional salvage therapies.
    •Fertile male patients must use a condom during sexual contact with a pregnant female or a FCBP while taking lenalidomide, during dose interruptions and for at least 28 days after the last dose of lenalidomide, even if he has undergone a successful vasectomy.
    •Female patients must be in menopause (natural menopause for at least 24 consecutive months, a hysterectomy, or bilateral oophorectomy) to enter the study
    •Karnofsky score > 60% at study entry
    •Patients fitness will be evaluated according to the SIE, SIES and GITMO Guidelines (Ferrara et al, Leukemia 2013)
    •Adequate renal, pulmonary and hepatic function, intended as follows:
    o Bilirubin = 2.5 times upper limit of normal (ULN) (unless elevation is due primarily to elevated unconjugated hyperbilirubinemia secondary to Gilbert's syndrome or hemolysis, but not to liver dysfunction)
    o AST and ALT = 3.5 times ULN
    o Creatinine = 2 times ULN
    • Diagnosi di recidiva LAM. E’ necessario che la precedente RC sia durata almeno 2 mesi per soddisfare la definizione di LAM recidivata. I pazienti non devono avere ricevuto più di 1 ciclo di reinduzione prima di entrare nello studio.
    • Diagnosi di LAM resistente. I pazienti devono non devono aver ricevuto più di 2 cicli di terapia (un ciclo di induzione e un ciclo di salvataggio) prima della terapia oggetto di studio per essere eleggibili all’arruolamento
    • I pazienti sottoposti in precedenza a trapianto di midollo osseo autologo o allogenico sono arruolabili.
    • Negatività al virus HIV.
    • Pazienti maschi e femmine di età = 60 e = 70 anni.
    • Consenso informato firmato
    • Diagnosi morfologica di leucemia acuta mieloide (LAM) non M3 in primo o successiva ricaduta, eseguita con aspirato midollare.
    • Globuli bianchi nel sangue periferico = 30.000/mm³. Un pre-trattamento con singola dose di vinblastina per ridurre il numero dei globuli bianchi è consentito entro 7 giorni dall'inizio della terapia. La citoriduzione con idrossiurea non è permessa.
    • Il paziente non deve essere eleggibile per o non è interessato a terapie tradizionali di salvataggio.
    • I pazienti maschi in età fertile devono utilizzare il preservativo durante i rapporti sessuali con una donna in stato di gravidanza o di un FCBP durante l'assunzione di lenalidomide , durante le interruzioni della dose e per almeno 28 giorni dopo l'ultima dose di lenalidomide , anche se ha subito con successo una vasectomia.
    • Le pazienti femmine devono essere in menopausa (menopausa naturale per almeno 24 mesi consecutivi , un intervento di isterectomia o ovariectomia bilaterale) per entrare nello studio.
    • Karnofsky score > 60% all'inizio dello studio
    • La fitness dei pazienti sarà valutata in base alle linee guida SIE, SIES e GITMO (Ferrara et al, Leukemia 2013)
    • Adeguata funzionalità renale, polmonare ed epatica, intesa come segue:
    o bilirubina = 2,5 volte il limite superiore del valore normale (ULN) (a meno che l’aumento sia dovuto principalmente alla elevata iperbilirubinemia non coniugata secondaria a sindrome o emolisi di Gilbert, ma non a disfunzione epatica)
    o AST e ALT = 3,5 volte ULN
    o Creatinina = 2 volte ULN
    E.4Principal exclusion criteria
    • Acute promyelocytic leukemia (FAB M3)
    • Cytoreduction with hydroxyurea
    • Male and female patients aged <60 years and >70 years
    • Patients with resistant AML who have received more than 2 courses or more of reinduction chemotherapy
    • Blastic transformation of chronic myeloid leukemia
    • Absence of patient’s written informed consent
    • Active opportunistic infections
    • HIV infection
    • Active second malignancy
    • Intercurrent organ damage or medical problems that would interfere with therapy
    • Concurrent therapy for another malignancy
    • Leucemia acuta promielocitica (FAB M3)
    • Citoriduzione con idrossiurea
    • Pazienti maschi e femmine di età compresa tra <60 anni e> 70 anni
    • I pazienti con leucemia acuta mieloide resistente che hanno ricevuto più di 2 o più cicli di chemioterapia di reinduzione
    • Trasformazione blastica di leucemia mieloide cronica
    • Assenza di consenso informato scritto del paziente
    • Infezioni opportunistiche attive
    • Infezione da HIV
    • Secondo tumore maligno attivo
    • Danno d'organo intercorrente o problemi di salute che potrebbero interferire con la terapia
    • Terapia concomitante per un altro tumore maligno.
    E.5 End points
    E.5.1Primary end point(s)
    To assess the complete remission (CR) rate, including CRi
    Determinare il tasso di remissioni complete (RC), incluse le RC con ricostituzione ematologica incompleta (RCi)
    E.5.1.1Timepoint(s) of evaluation of this end point
    Start: march 2016

    End Accrual Phase II: september 2017

    Final Study Report: december 2019
    Inizio: marzo 2016

    Fine Arruolamento della Fase II: settembre 2017

    Report Finale dello studio: dicembre 2019
    E.5.2Secondary end point(s)
    To assess overall survival.To assess event-free survival. To assess safety of the combination regimen, considered as the incidence of adverse event (graded according to WHO) and clinically significant abnormal laboratory values following chemotherapy. To assess the relationship of cytogenetic and molecular findings with response to treatment
    Determinare la sopravvivenza globale.Determinare la sopravvivenza libera da eventi. Determinare la sicurezza del regime di combinazione, in termini di incidenza di eventi avversi (classificati secondo la WHO) e di alterazioni laboratoristiche clinicamente significative in seguito al trattamento chemioterapico.Determinare la correlazione tra le anomalie citogenetiche e la risposta al trattamento.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Start: march 2016

    End Accrual Phase II: september 2017

    Final Study Report: december 2019
    Inizio: marzo 2016

    Fine Arruolamento della Fase II: settembre 2017

    Report Finale dello studio: dicembre 2019
    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 No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned12
    E.8.5The trial involves multiple Member States No
    E.8.5.1Number of sites anticipated in the EEA12
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    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
    LVLS
    LVLS
    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 months36
    E.8.9.1In the Member State concerned days10
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months36
    E.8.9.2In all countries concerned by the trial days10
    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: 15
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 51
    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 state66
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 66
    F.4.2.2In the whole clinical trial 66
    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)
    Normal clinical practice
    Normale pratica clinica
    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 Decision2016-10-18
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-11-10
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    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-Wed May 08 03:32:05 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA