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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 oppdatert av: 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.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Studietype

Intervensjonell

Registrering (Faktiske)

79

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Frankrike
      • AMIENS Cedex 1, Frankrike, 80054
        • CHU d'Amiens - Hôpital Sud
      • ANGERS Cedex 09, Frankrike, 49933
        • CHU Angers
      • Aix-en-Provence cedex 1, Frankrike, 13616
        • Centre Hospitalier du Pays d'Aix
      • Argenteuil Cedex, Frankrike, 95107
        • Centre Hospitalier Victor Dupouy
      • BESANÇON Cedex, Frankrike, 25030
        • CHU de Besançon - Hôpital Jean Minjoz
      • BREST Cedex, Frankrike, 29609
        • Chu de Brest - Hopital Morvan
      • Bayonne, Frankrike, 64100
        • Centre Hospitalier de la Côte Basque
      • Caen, Frankrike, 14000
        • "CHU Cote de nacre "
      • Clermont Ferrand, Frankrike, 63003
        • CHU Estaing
      • Creteil, Frankrike, 94010
        • AP-HP - Hôpital Henri Mondor
      • DIJON Cedex, Frankrike, 21079
        • CHRU de Dijon
      • Grenoble cedex 9, Frankrike, 38043
        • CHU de GRENOBLE
      • LE CHESNAY Cedex, Frankrike, 78157
        • Ch de Versailles - Hopital Andre Mignot
      • LILLE Cedex, Frankrike, 59037
        • CHRU de Lille
      • LIMOGES Cedex, Frankrike, 87042
        • C H U de Limoges - Hôpital Dupuytren
      • Lille Cedex, Frankrike, 59020
        • Groupe Hospitalier de l'Institut Catholique de Lille, hôpital Saint-Vincent
      • MEAUX Cedex, Frankrike, 77104
        • CH de Meaux
      • MONTPELLIER Cedex 5, Frankrike, 34295
        • Hôpital Saint-Eloi
      • MULHOUSE Cedex, Frankrike, 68070
        • CH de Mulhouse - Hôpital Emile Muller
      • Marseille cedex 9, Frankrike, 13273
        • Institut Paoli-Calmettes
      • Nantes, Frankrike, 44000
        • CHU Hôtel Dieu, Nantes
      • Nice, Frankrike, 06200
        • Chu de Nice - Hôpital L'Archet 1
      • ORLEANS Cedex, Frankrike, 45032
        • CHR d'Orléans - hôpital La Source
      • PARIS Cedex 10, Frankrike, 75010
        • AP-HP - Hôpital Saint Louis
      • PARIS Cedex 15, Frankrike, 75743
        • AP-HP - Hôpital Necker
      • PARIS cedex 12, Frankrike, 75571
        • AP-HP - hôpital Saint-Antoine
      • PERPIGNAN cedex 09, Frankrike, 66046
        • CH de Perpignan - Hôpital Saint-Jean
      • PESSAC Cedex, Frankrike, 33604
        • CHU de Bordeaux - Hôpital Haut-Lévêque
      • POITIERS Cedex, Frankrike, 86021
        • CHU de Poitiers - Hôpital la Milétrie
      • Pierre-Bénite Cedex, Frankrike, 69495
        • Centre Hospitalier LYON SUD
      • Pringy Cedex, Frankrike, 74374
        • CH de la Region d'Annecy
      • REIMS Cedex, Frankrike, 51092
        • CHU de Reims - Hôpital Robert Debré
      • RENNES Cedex 9, Frankrike, 35033
        • CHU de Rennes, Hopital Pontchaillou
      • Rouen Cedex 1, Frankrike, 76038
        • Centre Henri Becquerel, ROUEN
      • SAINT DENIS Cedex, Frankrike, 97405
        • CHU de la Réunion - Hôpital Felix Guyon
      • STRASBOURG Cedex, Frankrike, 67098
        • CHRU de Strasbourg - Hôpital Hautepierre
      • TOULON Cedex 9, Frankrike, 83041
        • Hia Sainte Anne
      • TOURS Cedex 9, Frankrike, 37044
        • CHRU de Tours - Hopital Bretonneau
      • Toulouse, Frankrike, 31100
        • "Institut Universitaire du Cancer (CHU de Toulouse - Hôpital Purpan)"
      • VALENCIENNES Cedex, Frankrike, 59322
        • Centre Hospitalier de Valenciennes
      • Vandoeuvre Les Nancy, Frankrike, 54511
        • CHU de Nancy - Hôpital Brabois
  • Spania
      • Barcelona, Spania, 08036
        • Hospital Clinic de Barcelona
      • Barcelona, Spania, 08916
        • Hospital Universitario Germans Trias i Pujol (ICO - Badalona)
      • Madrid, Spania, 28041
        • Hospital Universitario 12 De Octubre (Madrid)
      • Salamanca, Spania, 37007
        • Hospital Clínico Universitario de Salamanca
      • Sevilla, Spania, 41013
        • Hospital Universitario Virgen del Rocío (Sevilla)
      • Valencia, Spania, 46026
        • Hospital Universitario y Politécnico La Fe (Valencia)
  • Tyskland
      • Aachen, Tyskland, 52074
        • Uniklinik Aachen
      • Berlin, Tyskland, 13353
        • Charite 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 Nürnberg 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
        • Universitätsklinikum Essen
      • Münster, NRW, Tyskland, 48149
        • Universitätsklinik Münster
    • Niedersachsen
      • Hannover, Niedersachsen, Tyskland, 30625
        • Medizinische Hochschule Hannover
    • Sachsen
      • Dresden, Sachsen, Tyskland, 01307
        • Universitatsklinik Dresden

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

55 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

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

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Intervensjonsmodell: Enkeltgruppeoppdrag
  • Masking: Ingen (Open Label)

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
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
Tiltaksbeskrivelse
Tidsramme
Total overlevelse
Progresjonsfri overlevelse
Begivenhetsfri overlevelse
Tilbakefallsfri 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

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Goethe University

Etterforskere

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

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Hjelpsomme linker

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. januar 2012

Primær fullføring (Faktiske)

10. mars 2020

Studiet fullført (Faktiske)

10. mars 2020

Datoer for studieregistrering

Først innsendt

3. februar 2012

Først innsendt som oppfylte QC-kriteriene

3. februar 2012

Først lagt ut (Anslag)

7. februar 2012

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

30. juli 2020

Siste oppdatering sendt inn som oppfylte QC-kriteriene

29. juli 2020

Sist bekreftet

1. juli 2020

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

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

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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