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Evaluation of Efficacy and Safety of Nilotinib in Combination With Chemotherapy in Elderly Patients With Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

29. juli 2020 opdateret af: Heike Pfeifer MD, Goethe University

An Open Label Phase II Study to Evaluate the Efficacy and Safety of Induction and Consolidation Therapy With Nilotinib in Combination With Chemotherapy in Patients Aged 55 Years and Over With Philadelphia Chromosome Positive (Ph+ or BCR-ABL+) Acute Lymphoblastic Leukemia (ALL)

The goal of this trial is to evaluate the efficacy and the tolerance of the combination of nilotinib with chemotherapy in the front-line setting as induction and consolidation therapy in Ph+ ALL patient aged 55 years and over. A European consensus has been reached to adopt a common chemotherapeutic schedule for patients aged 55 years and over. This schedule will be used in this trial with the addition of nilotinib as concomitant therapy during induction, consolidation and maintenance. The patients will be prospectively monitored for minimal residual disease and bcr-abl tyrosine kinase domain mutations.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

79

Fase

  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Frankrig
      • AMIENS Cedex 1, Frankrig, 80054
        • CHU d'Amiens - Hôpital Sud
      • ANGERS Cedex 09, Frankrig, 49933
        • CHU Angers
      • Aix-en-Provence cedex 1, Frankrig, 13616
        • Centre Hospitalier du Pays d'Aix
      • Argenteuil Cedex, Frankrig, 95107
        • Centre Hospitalier Victor Dupouy
      • BESANÇON Cedex, Frankrig, 25030
        • CHU de Besancon - Hopital Jean Minjoz
      • BREST Cedex, Frankrig, 29609
        • CHU de Brest - Hôpital Morvan
      • Bayonne, Frankrig, 64100
        • Centre Hospitalier de la Cote Basque
      • Caen, Frankrig, 14000
        • "CHU Cote de nacre "
      • Clermont Ferrand, Frankrig, 63003
        • CHU Estaing
      • Creteil, Frankrig, 94010
        • AP-HP - Hôpital Henri Mondor
      • DIJON Cedex, Frankrig, 21079
        • CHRU de Dijon
      • Grenoble cedex 9, Frankrig, 38043
        • CHU de Grenoble
      • LE CHESNAY Cedex, Frankrig, 78157
        • Ch de Versailles - Hopital Andre Mignot
      • LILLE Cedex, Frankrig, 59037
        • CHRU de Lille
      • LIMOGES Cedex, Frankrig, 87042
        • C H U de Limoges - Hôpital Dupuytren
      • Lille Cedex, Frankrig, 59020
        • Groupe Hospitalier de l'Institut Catholique de Lille, hôpital Saint-Vincent
      • MEAUX Cedex, Frankrig, 77104
        • CH de Meaux
      • MONTPELLIER Cedex 5, Frankrig, 34295
        • Hopital Saint-Eloi
      • MULHOUSE Cedex, Frankrig, 68070
        • CH de Mulhouse - Hôpital Emile Muller
      • Marseille cedex 9, Frankrig, 13273
        • Institut Paoli-Calmettes
      • Nantes, Frankrig, 44000
        • CHU Hôtel Dieu, Nantes
      • Nice, Frankrig, 06200
        • Chu de Nice - Hôpital L'Archet 1
      • ORLEANS Cedex, Frankrig, 45032
        • CHR d'Orléans - hôpital La Source
      • PARIS Cedex 10, Frankrig, 75010
        • AP-HP - Hôpital Saint Louis
      • PARIS Cedex 15, Frankrig, 75743
        • AP-HP - Hôpital Necker
      • PARIS cedex 12, Frankrig, 75571
        • AP-HP - hôpital Saint-Antoine
      • PERPIGNAN cedex 09, Frankrig, 66046
        • CH de Perpignan - Hôpital Saint-Jean
      • PESSAC Cedex, Frankrig, 33604
        • Chu de Bordeaux - Hopital Haut-Leveque
      • POITIERS Cedex, Frankrig, 86021
        • CHU de Poitiers - Hôpital la Milétrie
      • Pierre-Bénite Cedex, Frankrig, 69495
        • Centre Hospitalier Lyon Sud
      • Pringy Cedex, Frankrig, 74374
        • CH de la région d'Annecy
      • REIMS Cedex, Frankrig, 51092
        • CHU de Reims - Hôpital Robert Debré
      • RENNES Cedex 9, Frankrig, 35033
        • CHU de Rennes, Hopital Pontchaillou
      • Rouen Cedex 1, Frankrig, 76038
        • Centre Henri Becquerel, Rouen
      • SAINT DENIS Cedex, Frankrig, 97405
        • CHU de la Réunion - Hôpital Felix Guyon
      • STRASBOURG Cedex, Frankrig, 67098
        • CHRU de Strasbourg - Hôpital Hautepierre
      • TOULON Cedex 9, Frankrig, 83041
        • HIA Sainte Anne
      • TOURS Cedex 9, Frankrig, 37044
        • CHRU de Tours - Hôpital Bretonneau
      • Toulouse, Frankrig, 31100
        • "Institut Universitaire du Cancer (CHU de Toulouse - Hôpital Purpan)"
      • VALENCIENNES Cedex, Frankrig, 59322
        • Centre Hospitalier de Valenciennes
      • Vandoeuvre Les Nancy, Frankrig, 54511
        • CHU de Nancy - Hôpital Brabois
  • Spanien
      • Barcelona, Spanien, 08036
        • Hospital Clinic de Barcelona
      • Barcelona, Spanien, 08916
        • Hospital Universitario Germans Trias i Pujol (ICO - Badalona)
      • Madrid, Spanien, 28041
        • Hospital Universitario 12 de Octubre (Madrid)
      • Salamanca, Spanien, 37007
        • Hospital Clínico Universitario de Salamanca
      • Sevilla, Spanien, 41013
        • Hospital Universitario Virgen del Rocío (Sevilla)
      • Valencia, Spanien, 46026
        • Hospital Universitario y Politécnico La Fe (Valencia)
  • Tyskland
      • Aachen, Tyskland, 52074
        • Uniklinik Aachen
      • Berlin, Tyskland, 13353
        • Charité Universitätsmedizin Berlin
      • Düsseldorf, Tyskland, 40225
        • University Hospital Düsseldorf
      • Göttingen, Tyskland, 37075
        • Universitätsklinikum Göttingen
      • Hamburg, Tyskland, 20099
        • Asklepios Klinik St. Georg
      • Kiel, Tyskland, 24116
        • Universitätsklinikum Schleswig-Holstein Campus Kiel
      • Leipzig, Tyskland, 04103
        • Universität Leipzig, José-Carreras-Haus
      • Mainz, Tyskland, 55101
        • Universitätskliniken Mainz
      • Mannheim, Tyskland, 68167
        • Klinikum Mannheim
      • München, Tyskland, 81377
        • Universitätsklinikum Großhadern
      • Nürnberg, Tyskland, 90419
        • Klinikum Nurnberg Nord
      • Oldenburg, Tyskland, 26133
        • Klinikum Oldenburg
      • Rostock, Tyskland, 18055
        • Universität Rostock
      • Ulm, Tyskland, 89070
        • Medizinische Universitätsklinik Ulm
      • Würzburg, Tyskland, 97080
        • Universität Würzburg
    • Baden-Württemberg
      • Stuttgart, Baden-Württemberg, Tyskland, 70376
        • Robert Bosch Krankenhaus
    • Bayern
      • Regensburg, Bayern, Tyskland, 93042
        • Klinikum der Universität Regensburg
    • Hessen
      • Frankfurt, Hessen, Tyskland, 60590
        • University Hospital of Frankfurt, Medical Dept. II
    • NRW
      • Essen, NRW, Tyskland, 45147
        • Universitatsklinikum Essen
      • Münster, NRW, Tyskland, 48149
        • Universitätsklinik Münster
    • Niedersachsen
      • Hannover, Niedersachsen, Tyskland, 30625
        • Medizinische Hochschule Hannover
    • Sachsen
      • Dresden, Sachsen, Tyskland, 01307
        • Universitatsklinik Dresden

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

55 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

  1. Male or female patients > 55 years
  2. Philadelphia chromosome- or BCR-ABL positive acute lymphoblastic leukemia
  3. Not previously treated except with corticosteroids or single dose vincristine (three doses cyclophosphamide accepted)
  4. With or without documented CNS involvement
  5. WHO performance status < 2
  6. Normal serum levels > LLN (lower limit of normal) of potassium, magnesium, total calcium corrected for serum albumin; or corrected to within normal limits with supplements, prior to the first dose of study medication
  7. Signed written inform consent
  8. Molecular evaluation for BCR-ABL performed
  9. Willingness of male subjects whose sexual partners are women of child-bearing potential (WOCBP), to use an effective form of contraception (pearl index < 1%), such as complete sexual abstinence, combined oral contraceptive, hormone IUCD, vaginal hormone ring, transdermal contraceptive patch, contraceptive implant or depot contraceptive injection in combination with a second method of contraception like a condom or a cervical cap / diaphragm with spermicide or surgical sterilisation (vasectomy) in male patients during the study and at least 6 months thereafter. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or surgical sterilization or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months).

Exclusion Criteria:

  1. Patient previously treated with tyrosine kinase inhibitors

  2. Known impaired cardiac function, including any of the following:

    • LVEF < 45%
    • Complete left bundle branch block
    • Right bundle branch block plus left anterior hemiblock, bifascicular block
    • Use of a ventricular-paced pacemaker
    • Congenital long QT syndrome
    • History of or presence of clinically significant ventricular or atrial tachyarrhythmias
    • Clinically significant resting bradycardia (< 50 beats per minute)
    • QTcF>450 msec on screening ECG. If QTc > 450 msec and electrolytes are not within normal ranges before nilotinib dosing, electrolytes should be corrected and then the patient rescreened for QTcF criterion.
    • Myocardial infarction with 12 months prior to starting nilotinib
    • Other clinical significant heart disease (e.g. unstable angina, congestive heart failure, uncontrolled hypertension)
  3. Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention
  4. Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory) or known infection with Hepatitis B or C
  5. Treatment with any, other investigational agent or participating in another trial within 30 days prior to entering this study
  6. Inadequate hepatic functions defined as ASAT or ALAT > 2,5 times the institutional upper limit of normal or > 5 times ULN if considered due to leukemia
  7. Total bilirubin > 2 fold the institutional upper limit unless considered to be due to organ involvement by the leukemia or to M. Gilbert / M. Meulengracht
  8. Concurrent severe diseases which exclude the administration of therapy
  9. Past history of acute or chronic pancreatits

  10. Patients unwilling or unable to comply with the protocol.e branch block; Right bundle branch block plus left anterior hemiblock, bifascicular block; Use of a ventricular-paced pacemaker; congenital long QT syndrome

    • History of or presence of clinically significant ventricular or atrial tachyarrhythmias
    • Clinically significant resting bradycardia (< 50 beats per minute)
    • QTcF>450 msec on screening ECG. If QTc > 450 msec and electrolytes are not within normal ranges before nilotinib dosing, electrolytes should be corrected and then the patient rescreened for QTcF criterion.
    • Myocardial infarction with 12 months prior to starting nilotinib

    • Other clinical significant heart disease (e.g. unstable angina, congestive heart failure, uncontrolled hypertension)

      • Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention
      • Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory) or known infection with Hepatitis B or C
      • Treatment with any, other investigational agent or participating in another trial within 30 days prior to entering this study
      • Inadequate hepatic functions defined as ASAT or ALAT > 2,5 times the institutional upper limit of normal or > 5 times ULN if considered due to leukemia
      • Total bilirubin > 2 fold the institutional upper limit unless considered to be due to organ involvement by the leukemia or to M. Gilbert / M. Meulengracht
      • Concurrent severe diseases which exclude the administration of therapy
      • Past history of acute or chronic pancreatits
      • Patients unwilling or unable to comply with the protocol.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Evaluation of efficacy of a nilotinib-based induction and consolidation therapy
Tidsramme: after 12 months
rate of patients without event
after 12 months

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Samlet overlevelse
Progressionsfri overlevelse
Begivenhedsfri overlevelse
Tilbagefaldsfri overlevelse
complete haematological remission
Tidsramme: after induction treatment (week 5)
The rate of complete haematological remission after induction treatment
after induction treatment (week 5)
major molecular response in bone marrow
major molecular response defined by a BCR-ABL/ABL < 0.1% in bone marrow
complete molecular response
complete molecular response defined by a BCR-ABL/ABL < 0.001% in bone marrow
undetectable BCR-ABL level
The proportion of patients with confirmed undetectable BCR-ABL level with a test sensitivity of at least 4.5 log.
T315I or p-loop Mutations
Detection of a T315I or p-loop BCR-ABL TK domain mutation
molecular relapse or progression
The proportion of patients with molecular relapse or progression
Tolerability
Tolerability as determined by descriptive assessment of adverse events and discontinuation due to treatment-related SAEs
Death during induction
Tidsramme: End of induction (week 5)
(all patients who started treatment)
End of induction (week 5)
Death in complete remission

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Goethe University

Efterforskere

  • Ledende efterforsker: Heike Pfeifer, Dr.med., Johann Wolfgang Goethe University Hospital

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Hjælpsomme links

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. januar 2012

Primær færdiggørelse (Faktiske)

10. marts 2020

Studieafslutning (Faktiske)

10. marts 2020

Datoer for studieregistrering

Først indsendt

3. februar 2012

Først indsendt, der opfyldte QC-kriterier

3. februar 2012

Først opslået (Skøn)

7. februar 2012

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

30. juli 2020

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

29. juli 2020

Sidst verificeret

1. juli 2020

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • EWALL-PH-02
  • 2010-022855-46 (EudraCT nummer)

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Kliniske forsøg med Nilotinib

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Betingelser

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Placeringer

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