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Nilotinib in PH+, BCR-, ABL+ CML Patients (CML0811)

3 augusti 2018 uppdaterad av: Gruppo Italiano Malattie EMatologiche dell'Adulto

The Protein Tyrosine Kinase Inhibitor Nilotinib as First-line Treatment of Ph+, BCR-, ABL+ Chronic Myeloid Leukemia (CML) in Early Chronic Phase: a Phase IIIb, Multicenter Study to Assess the Complete Molecular Response

This study is an open-label, multicentric, phase IIIb study of NILOTINIB administered orally twice daily for 24 months and indefinitely if it is in the interest of the patient.

The primary objective of the trial is to evaluate the efficacy of nilotinib, 300 mg twice daily with dose increase to 400 mg twice daily in case of suboptimal response or failure (excluding patients who will fail for progression to ABP), in a population of patients with Ph-positive, BCR-ABL positive CML in early CP.

Studieöversikt

Status

Avslutad

Betingelser

Intervention / Behandling

Detaljerad beskrivning

This study is an open-label, multicentric, phase IIIb study of NILOTINIB administered orally at the dose of 300 mg twice daily (total daily dose 600 mg daily) for 24 months (study core), and indefinitely if it is in the interest of the patient (the drug will be given free-of-charge after 24 months to all those patients achieving the CMR4 at 24 months and in absence of safety concerns). Nilotinib dose is increased to 400 mg BID in case of suboptimal response or failure (with the exception of patients who will fail for progression to ABP: in case of progression to ABP, the patient will not be treated with study drug and the choice of the treatment will be up to the physician).

Study duration is estimated in 6 years, 1 year of estimated enrollment, 2 years therapy duration. Thereafter, information on course and survival is due for other 3 years.

The main data analysis will be performed when all patients will complete 24 months of treatment (or discontinued earlier). Safety and tolerability profile will be assessed by collecting hematologic and non-hematologic adverse events, laboratory examinations and ECG data. The molecular response will be assessed using the GIMEMA standardized molecular laboratories (Labnet network).

Studietyp

Interventionell

Inskrivning (Förväntat)

109

Fas

  • Fas 3

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

  • Italien
      • Ancona, Italien
        • Azienda ospedaliera Nuovo Ospedale "Torrette"
      • Avellino, Italien
        • S.G. Moscati Hospital
      • Bologna, Italien, 40138
        • Azienda Ospedaliera Di Bologna Policlinico S. Orsola - Malpighi
      • Brescia, Italien, 25123
        • USD Trapianti di midollo per adulti - Cattedra di Ematologia - Università degli Studi di Brescia
      • Catania, Italien
        • Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto"
      • Catanzaro, Italien
        • Azienda Ospedaliera Pugliese Ciaccio - Presidio Ospedaliero A.Pugliese - Unità Operativa di Ematologia
      • Ferrara, Italien
        • Sezione di Ematologia e Fisiopatologia delle Emostasi - Azienda Ospedaliera - Arcispedale S. Anna
      • Foggia, Italien
        • Struttura Complessa di Ematologia Ospedali Riuniti Foggia - Azienda Ospedaliero-Universitaria
      • Genova, Italien
        • Clinica Ematologica - DiMI - Università degli Studi di Genova
      • Genova, Italien
        • Divisione Ematologia 1 - Azienda Ospedaliera Universitaria "San Martino"
      • Mestre, Italien
        • U.O. di Ematologia- Ospedale dell'Angelo - Mestre
      • Milano, Italien
        • U.O. Ematologia e Trapianto di MIdollo - Ist.Scientifico Ospedale San Raffaele
      • Modena, Italien
        • Centro Oncologico Modenese - Dipartimento di Oncoematologia
      • Padova, Italien
        • Università degli Studi di Padova - Ematologia ed Immunologia Clinica
      • Palermo, Italien, 90146
        • Ospedale Cervello
      • Palermo, Italien
        • Azienda Ospedaliera Universitaria - Policlinico Paolo Giaccone
      • Pesaro, Italien
        • Div. di Ematologia di Muraglia -CTMO Ospedale San Salvatore
      • Piacenza, Italien
        • Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale di Piacenza
      • Ravenna, Italien
        • Dipartimento Oncologico - Ospedale S.Maria delle Croci
      • Reggio Calabria, Italien
        • Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli"
      • Reggio Emilia, Italien
        • Unità Operativa Complessa di Ematologia - Arcispedale S. Maria Nuova
      • Rimini, Italien
        • Ospedale "Infermi"
      • Rionero in Vulture, Italien
        • IRCCS Centro di Riferimento Oncologico di Basilicata
      • Roma, Italien
        • Complesso Ospedaliero S. Giovanni Addolorata
      • Roma, Italien
        • Pronto Soccorso e Accettazione Ematologica - Dipartimento Biotecnologie Cellulari ed Ematologia - Università degli Studi di Roma "Sapienza"
      • Roma, Italien
        • U.O.C. Ematologia Ospedale S. Eugenio
      • Roma, Italien
        • Università degli Studi Policlinico di Tor Vergata
      • San Giovanni Rotondo, Italien
        • Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza
      • Siena, Italien
        • U.O.C. Ematologia e Trapianti - A.O. Senese - Policlinico " Le Scotte"
      • Taranto, Italien
        • U.O.C. di Ematolgia - A.O. " SS Annunziata" - P.O. S.G. Moscati
      • Torino, Italien
        • SCDO Ematologia 2 AOU S.Giovanni Battista
      • Treviso, Italien, 31100
        • Azienda USL 9 Treviso - U.O. di Ematologia
      • Udine, Italien
        • Clinica Ematologica - Policlinico Universitario
      • Verona, Italien
        • Università degli Studi di Verona - A. O. - Istituti Ospitalieri di Verona- Div. di Ematologia - Policlinico G.B. Rossi

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år och äldre (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

Inclusion Criteria:

  • Age ≥ 18
  • Male or female patients with diagnosis of Ph+ and/or BCR-ABL+ CML
  • Early chronic phase (within 6 months from diagnosis)
  • Pretreatment with Hydroxyurea or Anagrelide for a duration of up to 3 months and/or pretreatment with Imatinib for up to 30 days are permitted
  • Normal serum levels of potassium, magnesium, phosphorus, total calcium corrected for serum albumin or phosphorus, or correctable to within normal limits with supplements prior to the first dose of study medication
  • Written informed consent prior to any study procedures being performed
  • AST and ALT ≤ 2.5 x ULN or ≤ 5.0 x ULN if considered due to leukaemia
  • Alkaline phosphatase ≤ 2.5 x ULN unless considered due to leukaemia
  • Total direct bilirubin ≤ 1.5 x ULN, except know Mb. Gilbert
  • Serum creatinine ≤ 1.5 x ULN

Exclusion Criteria:

  • 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)
  • QTc>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 QTc criterion.
  • Myocardial infarction within 12 months prior to starting study drugs
  • Other clinical significant heart disease (e.g. unstable angina, congestive heart failure, uncontrolled hypertension)
  • Serum lipase and amylase > 1.5 x ULN (upper limit of normal) or history of acute (i.e., within 1 year of starting study medication) or chronic pancreatitis
  • Other concurrent uncontrolled medical conditions (e.g., uncontrolled diabetes, active or uncontrolled infections, acute or chronic liver and renal disease) that could cause unacceptable safety risks or compromise compliance with the protocol
  • Impaired gastrointestinal function or disease that may alter the absorption of study drug (e.g., ulcerative disease, uncontrolled nausea, vomiting and diarrhea, malabsorption syndrome, small bowel resection or gastric by-pass surgery)
  • Concomitant medications with potential QT prolongation (see link for complete list: http://www.torsades.org/medical-pros/drug-lists/printable-drug-list.cfm)
  • Concomitant medications known to interact with CYP450 isoenzymes (CYP3A4, CYP2C9,andCYP2C8:link for complete list: http://medicine.iupui.edu/flockhart/table.html..
  • Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
  • Patients who are pregnant or breast feeding, or women of reproductive potential not employing an effective method of birth control. (Women of childbearing potential must have a negative serum pregnancy test within 48 hours prior to administration of nilotinib).
  • Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention.
  • Patients unwilling or unable to comply with the protocol

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: N/A
  • Interventionsmodell: Enskild gruppuppgift
  • Maskning: Ingen (Open Label)

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Complete molecular response
Tidsram: At 24 months of treatment
To assess the complete molecular response (CMR4) rate at 24 months of treatment. For the purpose of this protocol, CMR is defined as a negative results of quantitative RT-PCR for BCR-ABL transcripts in a peripheral blood sample of at least 10 ml with a minimum sensitivity of 1:10,000, that corresponds to at least a 4-log reduction (hence, CMR4)
At 24 months of treatment

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Toxicity
Tidsram: At three years from study entry
Number of toxic events
At three years from study entry
Compliance
Tidsram: At 3 years from study entry
Number of fully compliant patients and number of patients who do not comply with treatment
At 3 years from study entry
The complete cytogenetic response (CCgR) rate
Tidsram: At 3, 6, 12, 18 and 24 months from study entry
At 3, 6, 12, 18 and 24 months from study entry
The rate and the degree of molecular response
Tidsram: At 3, 6, 12, 18 and 24 months from study entry
At 3, 6, 12, 18 and 24 months from study entry
The time to CCgR, the time to MMR and the time to CMR
Tidsram: baseline
baseline
Overall Survival (OS)
Tidsram: At three years from study entry
From the date of the first nilotinib dose to death
At three years from study entry
Progression Free Survival (PFS)
Tidsram: At three years from study entry
From the date of the first nilotinib dose to progression to AP or BP or death
At three years from study entry
Failure Free Survival (FFS)
Tidsram: At three years from study entry
From the date of the first nilotinib dose to failure* or progression or death
At three years from study entry
Event Free Survival (EFS)
Tidsram: At three years from study entry
From the date of the first nilotinib to any event. Including treatment discontinuation for adverse events, failure, progression to AP or BP, or death, whichever comes first.
At three years from study entry
Patient-reported quality of life (QoL)
Tidsram: At baseline and then at 3, 6, 12, 18 and 24 months
At baseline and then at 3, 6, 12, 18 and 24 months

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Gruppo Italiano Malattie EMatologiche dell'Adulto

Utredare

  • Studiestol: Gianantonio Rosti, Dpt of Hematology and Oncology, "Seràgnoli", Sant'Orsola-Malpighi. University Hospital of Bologna

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Allmänna publikationer

Användbara länkar

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

1 januari 2012

Primärt slutförande (Faktisk)

1 november 2014

Avslutad studie (Faktisk)

27 april 2018

Studieregistreringsdatum

Först inskickad

9 februari 2012

Först inskickad som uppfyllde QC-kriterierna

16 februari 2012

Första postat (Uppskatta)

17 februari 2012

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

6 augusti 2018

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

3 augusti 2018

Senast verifierad

1 augusti 2018

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • CML0811
  • 2011-002787-25 (EudraCT-nummer)

Plan för individuella deltagardata (IPD)

Planerar du att dela individuella deltagardata (IPD)?

Nej

Läkemedels- och apparatinformation, studiedokument

Studerar en amerikansk FDA-reglerad läkemedelsprodukt

Nej

Studerar en amerikansk FDA-reglerad produktprodukt

Nej

produkt tillverkad i och exporterad från U.S.A.

Nej

Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .

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