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Nilotinib Versus Standard Imatinib (400/600 mg Every Day (QD)) Comparing the Kinetics of Complete Molecular Response for Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) Pts With Evidence of Persistent Leukemia by Real-time Quantitative Polymerase Chain Reaction (RQ-PCR)

4 oktober 2016 bijgewerkt door: Novartis Pharmaceuticals

An Open Label, Randomized Study of Nilotinib vs. Standard Imatinib (400/600 mg QD) Comparing the Kinetics of Complete Molecular Response for CML-CP Patients With Evidence of Persistent Leukemia by RQ-PCR.

The primary goal of this study was to determine the rate of confirmed best cumulative complete molecular response (CMR) within the first year of study therapy with imatinib or nilotinib. The study also explored the impact and significance of the achieved CMR on patient outcomes (progression free survival (PFS), event free survival (EFS) and overall survival (OS), characterized the kinetics of CMR achieved in both treatment arms and after the cross-over.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Studietype

Ingrijpend

Inschrijving (Werkelijk)

207

Fase

  • Fase 3

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Argentinië
    • Buenos Aires
      • Caba, Buenos Aires, Argentinië, C1221ADH
        • Novartis Investigative Site
  • Australië
    • New South Wales
      • St. Leonards, New South Wales, Australië, 2065
        • Novartis Investigative Site
      • Westmead, New South Wales, Australië, 2145
        • Novartis Investigative Site
    • Queensland
      • Herston, Queensland, Australië, 4029
        • Novartis Investigative Site
      • South Brisbane, Queensland, Australië, 4101
        • Novartis Investigative Site
      • Woolloongabba, Queensland, Australië, 4102
        • Novartis Investigative Site
    • South Australia
      • Adelaide, South Australia, Australië, 5000
        • Novartis Investigative Site
    • Victoria
      • Parkville, Victoria, Australië, 3050
        • Novartis Investigative Site
      • Prahran, Victoria, Australië, 3181
        • Novartis Investigative Site
    • Western Australia
      • Nedlands, Western Australia, Australië, 6009
        • Novartis Investigative Site
  • Brazilië
    • MG
      • Belo Horizonte, MG, Brazilië, 30130-100
        • Novartis Investigative Site
    • PR
      • Curitiba, PR, Brazilië, 80060-900
        • Novartis Investigative Site
    • RJ
      • Rio de Janeiro, RJ, Brazilië, 21941-913
        • Novartis Investigative Site
    • SP
      • Campinas, SP, Brazilië, 13083-970
        • Novartis Investigative Site
      • Sao Paulo, SP, Brazilië, 05403-000
        • Novartis Investigative Site
  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 1M9
        • Novartis Investigative Site
    • Ontario
      • Hamilton, Ontario, Canada, L8H 4J9
        • Novartis Investigative Site
      • Toronto, Ontario, Canada, M5G 2M9
        • Novartis Investigative Site
    • Quebec
      • Montreal, Quebec, Canada, H1T 2M4
        • Novartis Investigative Site
      • Québec, Quebec, Canada, G1J 1Z4
        • Novartis Investigative Site
  • Frankrijk
      • Bordeaux, Frankrijk, 33076
        • Novartis Investigative Site
      • Creteil, Frankrijk, 94010
        • Novartis Investigative Site
      • Lyon cedex 04, Frankrijk, 69317
        • Novartis Investigative Site
      • Paris, Frankrijk, 75010
        • Novartis Investigative Site
      • Vandoeuvre les Nancy, Frankrijk, 54511
        • Novartis Investigative Site
  • Spanje
      • Madrid, Spanje, 28006
        • Novartis Investigative Site
      • Madrid, Spanje, 28007
        • Novartis Investigative Site
    • Andalucia
      • Malaga, Andalucia, Spanje, 29010
        • Novartis Investigative Site
    • Cataluña
      • Barcelona, Cataluña, Spanje, 08036
        • Novartis Investigative Site
    • Navarra
      • Pamplona, Navarra, Spanje, 31008
        • Novartis Investigative Site

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion Criteria:

Diagnosis of chronic myeloid leukemia associated with BCR-ABL quantifiable by RQ-PCR Documented CCyR by bone marrow or BCR-ABL<1% IS in the past 12 months Persistent disease demonstrated by two PCR positive tests 3 months apart both during the past 6 months.

Treatment with imatinib for at least 2 years with 400 mg or 600 mg and a stable dose No other current or planned anti-leukemia therapies

Exclusion Criteria:

Patient has evidence of rising PCR (a confirmed >1 log increase in previous 6 months) Patient has received another investigational agent within last 6 months or tyrosine kinase inhibitors (TKIs) other than imatinib Prior allogeneic stem cell transplantation

Impaired cardiac function including any one of the following:

Inability to monitor the QT interval on electrocardiogram (ECG) Long QT syndrome or a known family history of long QT syndrome. Clinically significant resting brachycardia (<50 beats per minute) QTc > 450 msec on baseline ECG (using the QTcF formula). If QTcF >450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc Myocardial infarction within 12 months prior to starting study Other clinically significant uncontrolled heart disease (e.g. unstable angina, congestive heart failure or uncontrolled hypertension) History of or presence of clinically significant ventricular or atrial tachyarrhythmias Administration of cytokine therapy (e.g. G-CSF, GM-CSF or SCF) within 4 weeks prior to study entry

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Nilotinib
Participants received Nilotinib 400 mg orally twice daily (bid) for 48 months.
Geneesmiddel: Nilotinib
Supplied in 200 mg capsules
Actieve vergelijker: Imatinib
Participants received Imatinib 400 mg or 600 mg once daily (qd) (based on the participant's dose prior to randomization) for 48 months.
Geneesmiddel: Imatinib
Supplied in 100 mg and 400 mg capsules
Andere namen:
  • Glivec/Gleevec

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Rate of Confirmed Best Cumulative Complete Molecular Response (CMR)
Tijdsspanne: 12 months
The rate of confirmed best cumulative CMR was defined as the number of participants who had confirmed CMR during the first 12 months of treatment after the randomization date. Participants who achieved confirmed best cumulative CMR during the first 12 months were considered responders. Participants who dropped out early or who did not provide sufficient data for any reason were considered to be non-responders. The definition of CMR is undetectable BCR-ABL (fusion gene formed between bcr gene from chromosome 22 and abl gene from chromosome 9) where BCR-ABL ratio in % international scale (IS) ≤ 0.00001 by real-time quantitative polymerase chain reaction (RQ-PCR) where there was no detectable BCR-ABL and 1) the test had a sensitivity of at least 4.5 logs below the standardized baseline; 2) RQ-PCR negativity was confirmed on the next RQ-PCR sample (usually 3 months later); and 3) the date of confirmed CMR was the date of the first of two negative results with sensitivity >4.5 logs.
12 months

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Rate of Confirmed Best Cumulative CMR
Tijdsspanne: 24 months, 36 month, 48 months
The rate of confirmed best cumulative CMR was defined as the number of participants who had confirmed CMR during the 24, 36 and 48 months post treatment after the randomization date. Participants who achieved confirmed best cumulative CMR during the first 12 months were considered responders. Participants who dropped out early or who did not provide sufficient data for any reason were considered to be non-responders. The definition of CMR is undetectable BCR-ABL (fusion gene formed between bcr gene from chromosome 22 and abl gene from chromosome 9) where BCR-ABL ratio in % international scale (IS) ≤ 0.00001 by RQ-PCR where there was no detectable BCR-ABL and 1) the test had a sensitivity of at least 4.5 logs below the standardized baseline; 2) RQ-PCR negativity was confirmed on the next RQ-PCR sample (usually 3 months later); and 3) the date of confirmed CMR was the date of the first of two negative results with sensitivity >4.5 logs.
24 months, 36 month, 48 months
Number of Cross-over Participants With CMR
Tijdsspanne: 24 months, 36 months, 48 months
The definition of CMR is undetectable BCR-ABL (fusion gene formed between bcr gene from chromosome 22 and abl gene from chromosome 9) where BCR-ABL ratio in % international scale (IS) ≤ 0.00001 by RQ-PCR where there was no detectable BCR-ABL and 1) the test had a sensitivity of at least 4.5 logs below the standardized baseline; 2) RQ-PCR negativity was confirmed on the next RQ-PCR sample (usually 3 months later); and 3) the date of confirmed CMR was the date of the first of two negative results with sensitivity >4.5 logs.
24 months, 36 months, 48 months
Progression Free Survival (PFS)
Tijdsspanne: 48 months
PFS was defined as the time from the date of randomization to the date of the earliest documented progression-defining event as follows: transformation to blast crisis or accelerated phase disease, or death from any cause.
48 months
Event-free Survival
Tijdsspanne: 48 months
Event-free survival was defined as the time from the date of randomization to the date of first occurrence of any of the following events on study treatment: loss of complete hematological response, confirmed loss of complete cytogenetic response (CCyR), confirmed loss of major molecular response (MMR), death from any cause during treatment, progression to the accelerated phase or blast crisis of chronic myelogenous leukemia (CML) per European Leukemia Network (ELN) criteria, whichever was earliest.
48 months
Overall Survival
Tijdsspanne: 48 months
Overall survival was defined as the time from the date of randomization to the date of death due to any cause at any time during the study, including the follow-up period after discontinuation of treatment.
48 months

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Novartis Pharmaceuticals

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 juni 2009

Primaire voltooiing (Werkelijk)

1 juli 2015

Studie voltooiing (Werkelijk)

1 juli 2015

Studieregistratiedata

Eerst ingediend

25 september 2008

Eerst ingediend dat voldeed aan de QC-criteria

25 september 2008

Eerst geplaatst (Schatting)

26 september 2008

Updates van studierecords

Laatste update geplaatst (Schatting)

8 november 2016

Laatste update ingediend die voldeed aan QC-criteria

4 oktober 2016

Laatst geverifieerd

1 oktober 2016

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • CAMN107A2405
  • 2009-012616-40 (EudraCT-nummer)

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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