Nilotinib in Newly Diagnosed Adult Philadelphia Chromosome and /or BCR-ABL Positive Chronic Myeloid Leukaemia in Chronic Phase

Leukemia, Myeloid Clinical Trial

— `MACS1252  

Official title:

A Phase IIIb, Multicentre, Open-label Study of Nilotinib in Adult Patients With Newly Diagnosed Philadelphia Chromosome and/or BCR-ABL Positive CML in Chronic Phase

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01061177
• Other study ID #: CAMN107EIC01
• Secondary ID: 2009-017775-19
• Status: Completed
• Phase: Phase 4
• First received: February 1, 2010
• Last updated: October 2, 2014
• Start date: May 2010
• Est. completion date: July 2014

Study information

• Verified date: October 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationAustria: Federal Office for Safety in Health CareBelgium: Federal Agency for Medicinal Products and Health ProductsBosnia: Federal Ministry of HealthBulgaria: Bulgarian Drug AgencyCroatia: Ministry of Health and Social CareCzech Republic: State Institute for Drug ControlDenmark: Danish Medicines AgencyEstonia: The State Agency of MedicineFinland: Finnish Medicines AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesGreece: National Organization of MedicinesItaly: The Italian Medicines AgencyLatvia: State Agency of MedicinesLithuania: State Medicine Control Agency - Ministry of HealthNetherlands: Medicines Evaluation Board (MEB)Norway: Norwegian Medicines AgencyPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsPortugal: National Pharmacy and Medicines InstituteRomania: National Medicines AgencySerbia and Montenegro: Agency for Drugs and Medicinal DevicesSlovakia: State Institute for Drug ControlSlovenia: Agency for Medicinal Products - Ministry of HealthSpain: Spanish Agency of MedicinesSweden: Medical Products AgencySwitzerland: SwissmedicUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

This study will assess the efficacy and safety of nilotinib in adult patients with newly diagnosed Philadelphia chromosome positive/BCR-ABL positive chronic myeloid leukaemia in chronic phase. The aim of the study is to confirm the rates of complete molecular remission (CMR) of nilotinib in newly diagnosed CML chronic phase patients in a pan-European population using the EUTOS standardized laboratories.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1088
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male or female patients with diagnosis of CP-CML with cytogenetic confirmation of Philadelphia (Ph) chromosome

2. Ph negative cases or patients with variant translocations who are BCR-ABL positive in multiplex PCR are also eligible

3. WHO performance status 0-2

4. Laboratory assessments within normal limits

5. Written informed consent prior to any study procedures being performed

Exclusion Criteria:

1. Known impaired cardiac function

2. History of acute or chronic pancreatitis

3. Impaired gastrointestinal function or disease that may alter the absorption of study drug

4. Concomitant medications with potential QT prolongation, or known to interact with CYP450 isoenzymes (CYP3A4, CYP2C9, and CYP2C8)

5. Patients who have undergone major surgery = 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy

6. Patients who are pregnant or breast feeding, or females of reproductive potential not employing an effective method of birth control. Female patients must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug

Other protocol-defined inclusion/exclusion criteria may apply

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia, Myeloid
• Philadelphia Chromosome

Intervention

Drug:
• Nilotinib

Locations

Country	Name	City	State
Austria	Novartis Investigative Site	Graz
Austria	Novartis Investigative Site	Innsbruck
Austria	Novartis Investigative Site	Linz
Austria	Novartis Investigative Site	Rankweil
Austria	Novartis Investigative Site	Salzburg
Austria	Novartis Investigative Site	Vienna
Austria	Novartis Investigative Site	Wels
Austria	Novartis Investigative Site	Wien
Belgium	Novartis Investigative Site	Aalst
Belgium	Novartis Investigative Site	Brugge
Belgium	Novartis Investigative Site	Brussel
Belgium	Novartis Investigative Site	Brussels
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Charleroi
Belgium	Novartis Investigative Site	Edegem
Belgium	Novartis Investigative Site	Gent
Belgium	Novartis Investigative Site	Godinne
Belgium	Novartis Investigative Site	Hasselt
Belgium	Novartis Investigative Site	Laeken
Belgium	Novartis Investigative Site	Leuven
Belgium	Novartis Investigative Site	Luxembourg
Belgium	Novartis Investigative Site	Roeselare
Belgium	Novartis Investigative Site	Verviers
Bulgaria	Novartis Investigative Site	Pleven
Bulgaria	Novartis Investigative Site	Plovdiv
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Varna
Croatia	Novartis Investigative Site	Rijeka
Croatia	Novartis Investigative Site	Zagreb
Czech Republic	Novartis Investigative Site	Brno - Bohunice
Czech Republic	Novartis Investigative Site	Hradec Kralove
Czech Republic	Novartis Investigative Site	Olomouc	CZE
Czech Republic	Novartis Investigative Site	Praha 2
Denmark	Novartis Investigative Site	Aarhus C
Denmark	Novartis Investigative Site	Copenhagen
Denmark	Novartis Investigative Site	Odense C
Estonia	Novartis Investigative Site	Tartu
Finland	Novartis Investigative Site	HUS Helsinki
Finland	Novartis Investigative Site	Oulu
France	Novartis Investigative Site	Aix en Provence Cedex 1
France	Novartis Investigative Site	Amiens cedex1
France	Novartis Investigative Site	Angers Cedex 1
France	Novartis Investigative Site	Argenteuil Cedex
France	Novartis Investigative Site	Avignon cedex 9
France	Novartis Investigative Site	Bayonne
France	Novartis Investigative Site	Besancon cedex
France	Novartis Investigative Site	Blois Cedex
France	Novartis Investigative Site	Bordeaux
France	Novartis Investigative Site	Brest
France	Novartis Investigative Site	Caen
France	Novartis Investigative Site	Chalon sur Saône
France	Novartis Investigative Site	Chambéry cedex
France	Novartis Investigative Site	Clermont-Ferrand cedex 1
France	Novartis Investigative Site	Compiègne cedex
France	Novartis Investigative Site	Corbeil Essonnes
France	Novartis Investigative Site	Creteil
France	Novartis Investigative Site	Dijon
France	Novartis Investigative Site	Dunkerque
France	Novartis Investigative Site	Grenoble
France	Novartis Investigative Site	La Roche sur Yon cedex 9
France	Novartis Investigative Site	Le Chesnay
France	Novartis Investigative Site	Le Coudray
France	Novartis Investigative Site	Le Mans Cedex 09
France	Novartis Investigative Site	Lens Cedex
France	Novartis Investigative Site	Lille cedex
France	Novartis Investigative Site	Limoges cedex
France	Novartis Investigative Site	Mâcon Cedex
France	Novartis Investigative Site	Marseille
France	Novartis Investigative Site	Marseille cedex 20
France	Novartis Investigative Site	Metz Cedex 01
France	Novartis Investigative Site	Monte-Carlo	Principauté de Monaco
France	Novartis Investigative Site	Montfermeil
France	Novartis Investigative Site	Montpellier cedex 5
France	Novartis Investigative Site	Mulhouse cedex
France	Novartis Investigative Site	Nantes
France	Novartis Investigative Site	Nice Cedex 2
France	Novartis Investigative Site	Nimes
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Pau
France	Novartis Investigative Site	Perpignan
France	Novartis Investigative Site	Pringy cedex
France	Novartis Investigative Site	Reims
France	Novartis Investigative Site	Rennes
France	Novartis Investigative Site	Roubaix
France	Novartis Investigative Site	Rouen Cedex 1
France	Novartis Investigative Site	Saint Brieuc cedex 1
France	Novartis Investigative Site	Saint Denis	FRANCE / La Reunion
France	Novartis Investigative Site	Saint Priest en Jarez Cedex
France	Novartis Investigative Site	St Quentin Cedex
France	Novartis Investigative Site	Strasbourg cedex
France	Novartis Investigative Site	Strasbourg cedex
France	Novartis Investigative Site	Toulouse Cedex 9
France	Novartis Investigative Site	Tours Cedex 9
France	Novartis Investigative Site	Troyes
Germany	Novartis Investigative Site	Aachen
Germany	Novartis Investigative Site	Aschaffenburg
Germany	Novartis Investigative Site	Augsburg
Germany	Novartis Investigative Site	Bamberg
Germany	Novartis Investigative Site	Bayreuth
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bielefeld
Germany	Novartis Investigative Site	Bonn
Germany	Novartis Investigative Site	Bottrop
Germany	Novartis Investigative Site	Bremen
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Duesseldorf
Germany	Novartis Investigative Site	Duisburg
Germany	Novartis Investigative Site	Eisenach
Germany	Novartis Investigative Site	Eschweiler
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Frankfurt, Oder
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Fulda
Germany	Novartis Investigative Site	Giessen
Germany	Novartis Investigative Site	Goslar
Germany	Novartis Investigative Site	Greifswald
Germany	Novartis Investigative Site	Hagen
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamm
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Herrsching
Germany	Novartis Investigative Site	Hildesheim
Germany	Novartis Investigative Site	Jena
Germany	Novartis Investigative Site	Karlsruhe
Germany	Novartis Investigative Site	Karlsruhe
Germany	Novartis Investigative Site	Kassel
Germany	Novartis Investigative Site	Kassel
Germany	Novartis Investigative Site	Kiel
Germany	Novartis Investigative Site	Koblenz
Germany	Novartis Investigative Site	Köln
Germany	Novartis Investigative Site	Landshut
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Lemgo
Germany	Novartis Investigative Site	Luebeck
Germany	Novartis Investigative Site	Magdeburg
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Mannheim
Germany	Novartis Investigative Site	Marburg
Germany	Novartis Investigative Site	Moers
Germany	Novartis Investigative Site	Mönchengladbach
Germany	Novartis Investigative Site	Muelheim
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	München
Germany	Novartis Investigative Site	Mutlangen
Germany	Novartis Investigative Site	Neunkirchen
Germany	Novartis Investigative Site	Nuernberg
Germany	Novartis Investigative Site	Nuernberg
Germany	Novartis Investigative Site	Offenburg
Germany	Novartis Investigative Site	Paderborn
Germany	Novartis Investigative Site	Ravensburg
Germany	Novartis Investigative Site	Rostock
Germany	Novartis Investigative Site	Schorndorf
Germany	Novartis Investigative Site	Schwäbisch-Hall
Germany	Novartis Investigative Site	Sindelfingen
Germany	Novartis Investigative Site	Stuttgart
Germany	Novartis Investigative Site	Traunstein
Germany	Novartis Investigative Site	Triberg
Germany	Novartis Investigative Site	Ulm
Germany	Novartis Investigative Site	Velbert
Germany	Novartis Investigative Site	Viersen
Germany	Novartis Investigative Site	Weilheim
Germany	Novartis Investigative Site	Wendlingen
Germany	Novartis Investigative Site	Wuerzburg
Germany	Novartis Investigative Site	Würzburg
Germany	Novartis Investigative Site	Zella-Mehlis
Greece	Novartis Investigative Site	Athens	GR
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Heraklion Crete	GR
Greece	Novartis Investigative Site	Larissa	GR
Greece	Novartis Investigative Site	Patras
Greece	Novartis Investigative Site	Thessaloniki	GR
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Debrecen
Hungary	Novartis Investigative Site	Kaposvár
Hungary	Novartis Investigative Site	Pecs
Hungary	Novartis Investigative Site	Szeged
Italy	Novartis Investigative Site	Ancona	AN
Italy	Novartis Investigative Site	Avellino	AV
Italy	Novartis Investigative Site	Bari	BA
Italy	Novartis Investigative Site	Bologna	BO
Italy	Novartis Investigative Site	Brescia	BS
Italy	Novartis Investigative Site	Brindisi	BR
Italy	Novartis Investigative Site	Cagliari	CA
Italy	Novartis Investigative Site	Cagliari	CA
Italy	Novartis Investigative Site	Catanzaro	CZ
Italy	Novartis Investigative Site	Cona	FE
Italy	Novartis Investigative Site	Cuneo	CN
Italy	Novartis Investigative Site	Firenze	FI
Italy	Novartis Investigative Site	Genova	GE
Italy	Novartis Investigative Site	Lecce	LE
Italy	Novartis Investigative Site	Livorno	LI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Modena	MO
Italy	Novartis Investigative Site	Napoli
Italy	Novartis Investigative Site	Napoli
Italy	Novartis Investigative Site	Nocera Inferiore	SA
Italy	Novartis Investigative Site	Novara
Italy	Novartis Investigative Site	Nuoro	NU
Italy	Novartis Investigative Site	Orbassano	TO
Italy	Novartis Investigative Site	Padova	PD
Italy	Novartis Investigative Site	Palermo	PA
Italy	Novartis Investigative Site	Pavia	PV
Italy	Novartis Investigative Site	Perugia
Italy	Novartis Investigative Site	Pesaro	PU
Italy	Novartis Investigative Site	Pescara	PE
Italy	Novartis Investigative Site	Pisa	PI
Italy	Novartis Investigative Site	Potenza	PZ
Italy	Novartis Investigative Site	Ravenna	RA
Italy	Novartis Investigative Site	Reggio Calabria	RC
Italy	Novartis Investigative Site	Reggio Emilia	RE
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Ronciglione	VT
Italy	Novartis Investigative Site	Rossano	CS
Italy	Novartis Investigative Site	San Giovanni Rotondo	FG
Italy	Novartis Investigative Site	Sassari	SS
Italy	Novartis Investigative Site	Siena	SI
Italy	Novartis Investigative Site	Taranto	TA
Italy	Novartis Investigative Site	Terni	TR
Italy	Novartis Investigative Site	Torino	TO
Italy	Novartis Investigative Site	Treviso	TV
Latvia	Novartis Investigative Site	Riga	LV
Lithuania	Novartis Investigative Site	Kaunas
Lithuania	Novartis Investigative Site	Klaipeda
Lithuania	Novartis Investigative Site	Vilnius
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Delft
Netherlands	Novartis Investigative Site	Enschede
Netherlands	Novartis Investigative Site	Groningen
Netherlands	Novartis Investigative Site	Nijmegen
Netherlands	Novartis Investigative Site	Rotterdam
Netherlands	Novartis Investigative Site	Zwolle
Norway	Novartis Investigative Site	Bergen
Norway	Novartis Investigative Site	Oslo
Norway	Novartis Investigative Site	Stavanger
Norway	Novartis Investigative Site	Tromsø
Norway	Novartis Investigative Site	Trondheim
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Krakow
Poland	Novartis Investigative Site	Lublin
Poland	Novartis Investigative Site	Warsaw
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Wroclaw
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Porto
Portugal	Novartis Investigative Site	Porto
Romania	Novartis Investigative Site	Bucharest	District 2
Romania	Novartis Investigative Site	Bucharest
Romania	Novartis Investigative Site	Bucharest
Romania	Novartis Investigative Site	Cluj-Napoca
Romania	Novartis Investigative Site	Iasi	Jud. Iasi
Romania	Novartis Investigative Site	Timisoara
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Kosice	Slovak Republic
Slovakia	Novartis Investigative Site	Martin
Slovenia	Novartis Investigative Site	Celje
Slovenia	Novartis Investigative Site	Ljubljana
Spain	Novartis Investigative Site	Badalona	Catalunya
Spain	Novartis Investigative Site	Baracaldo	Pais Vasco
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Bilbao	Pais Vasco
Spain	Novartis Investigative Site	Elche	Murcia
Spain	Novartis Investigative Site	La Coruna	Galicia
Spain	Novartis Investigative Site	La Laguna	Las Palmas de Gran Canaria
Spain	Novartis Investigative Site	Las Palmas de Gran Canaria	Las Palmas de G.C
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Majadanonda	Madrid
Spain	Novartis Investigative Site	Murcia
Spain	Novartis Investigative Site	Orense	Galicia
Spain	Novartis Investigative Site	Oviedo	Asturias
Spain	Novartis Investigative Site	Pamplona	Navarra
Spain	Novartis Investigative Site	Salamanca	Castilla y Leon
Spain	Novartis Investigative Site	San Sebastian	Pais Vasco
Spain	Novartis Investigative Site	Santander	Cantabria
Spain	Novartis Investigative Site	Tarragona	Cataluña
Spain	Novartis Investigative Site	Terrassa	Cataluña
Spain	Novartis Investigative Site	Toledo	Castilla la Mancha
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Zaragoza
Sweden	Novartis Investigative Site	Göteborg
Sweden	Novartis Investigative Site	Huddinge
Sweden	Novartis Investigative Site	Linköping
Sweden	Novartis Investigative Site	Luleå
Sweden	Novartis Investigative Site	Lund
Sweden	Novartis Investigative Site	Stockholm
Sweden	Novartis Investigative Site	Umeå
Sweden	Novartis Investigative Site	Uppsala
Switzerland	Novartis Investigative Site	Bern
Switzerland	Novartis Investigative Site	Chur
Switzerland	Novartis Investigative Site	Genève
Switzerland	Novartis Investigative Site	Zurich
United Kingdom	Novartis Investigative Site	Cardiff
United Kingdom	Novartis Investigative Site	Dudley
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Nottingham
United Kingdom	Novartis Investigative Site	Oxford
United Kingdom	Novartis Investigative Site	Uxbridge	London

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Austria,  Belgium,  Bulgaria,  Croatia,  Czech Republic,  Denmark,  Estonia,  Finland,  France,  Germany,  Greece,  Hungary,  Italy,  Latvia,  Lithuania,  Netherlands,  Norway,  Poland,  Portugal,  Romania,  Slovakia,  Slovenia,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of complete molecular response (CMR). Levels of BCR-ABL transcripts will be determined by RQ-PCR testing of peripheral blood and analysed at an appropriate national EUTOS reference laboratory.	CMR is defined as undetectable BCR-ABL transcripts by quantitative RT-PCR in a peripheral blood sample of at least 10 ml with a minimum sensitivity of 1:10,000.	after 18 months of study drug	No
Secondary	Rate of early progression to accelerated phase and blast crisis in year 1 and 2 and the rate of events in patients achieving a CMR at 1 year		at 12 and 24 months	No
Secondary	The rate of MMR at, as well as by, 12 and 24 months; the rate of CCyR at, as well as by , 12 and 24 months; the rate of CHR at, as well as by, 12 and 24 months		at as welll as by 12 and 24 months	No
Secondary	The rate of early events, event free survival, overall survival; and safety and tolerability of nilotinib		at 12 and 24 months	No
Secondary	Exploratory endpoints patterns	Exploratory endpoints include the kinetics of MMR and the dynamics of molecular response and potential patterns	at, as well as, by 3, 6, 9, 12, 15, 21, and 24 months	No