Clinical trial NCT00333840: Safety and Efficacy of Imatinib Versus Interferon-α Plus Cytarabine in Patients With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia
Official title: A Phase III Study of STI571 Versus Interferon-α (IFN-α) Combined With Cytarabine (Ara-C) in Patients With Newly Diagnosed Previously Untreated Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Myelogenous Leukemia
Keywords: CML
STI571
imatinib
interferon
interferon alpha
cytosine arabinoside
chronic myeloid leukemia
Philadelphia chromosome positive
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2006-06-06
Enrollment: 1106
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate and compare the side effects and anti-leukemic benefits of imatinib with those of interferon and Ara-C for patients who have chronic myeloid leukemia (CML) in the chronic phase. Patients in this study will be randomized (1:1) to receive either interferon plus Ara-C or imatinib as initial treatment.


Eligibility criteria: Inclusion criteria:

* Must have signed consent for Amendment 5
* Must have completed visit 62 of the core IRIS trial or be in follow-up
* Must be on STI571 treatment
* If on IFN treatment, must be willing to cross over to STI571 treatment

Exclusion criteria:

* Patients who have discontinued from the study and are in follow-up
* Patients who are on IFN treatment and do not want to cross over to STI571 treatment
* Patients who have not consented to amendment 5
* Patients who did not complete the amendment 5 protocol

Additional protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Kaplan-Meier Estimates of Overall Survival (All Randomized Participants)
timeFrame: 12,24,36,48,60,72,84,96,108,120,132 and 144 months
Secondary outcomes:
measure: Kaplan Meier Estimates of Event Free Survival (All Randomized Participants)
timeFrame: 12,24,36,48,60,72,84,96,108,120,132 and 144 months
measure: Percentage of Participants With Event Free Survival Events (All Randomized Participants)
timeFrame: 144 months
measure: Kaplan Meier Estimates of Time to Progression to Accelerated Phase (AP) or Blast Crisis (BC) (All Randomized Participants)
timeFrame: 12,24,36,48,60,72,84,96,108,120,132 and 144 months
measure: Percentage of Participants With Best Cytogenetic Response (First-line Treatment)
timeFrame: 144 months
measure: Percentage of Participants With Best Cytogenetic Response (Second-line Treatment)
timeFrame: 144 months
measure: Number of Participants With Serious Adverse Events as a Measure of Safety (First-line Treatment)
timeFrame: 144 months
measure: Number of Participants With Serious Adverse Events as a Measure of Safety (Second-line Treatment)
timeFrame: 144 months
measure: Percentage of Participants With Major Molecular Response (First-line Treatment)
timeFrame: 12,24,36,48,60,72,84,96,108,120,132 and 144 months
measure: Percentage of Participants With Major Molecular Response (Second-line Treatment)
timeFrame: 12,24,36,48,60,72,84,96,108,120,132 and 144 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Novartis Investigative Site
state: Alabama
city: Montgomery
country: United States
facility: Novartis Investigative Site
state: Alabama
city: Tucson
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Berkeley
country: United States
facility: Novartis Investigative Site
state: California
city: Campbell
country: United States
facility: Novartis Investigative Site
state: California
city: Duarte
country: United States
facility: Novartis Investigative Site
state: California
city: La Jolla
country: United States
facility: Novartis Investigative Site
state: California
city: Denver
country: United States
facility: Novartis Investigative Site
state: Colorado
city: Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: Orlando
country: United States
facility: Novartis Investigative Site
state: Florida
city: Atlanta
country: United States
facility: Novartis Investigative Site
state: Georgia
city: Honolulu
country: United States
facility: Novartis Investigative Site
state: Hawaii
city: Chicago
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Chicago
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Chicago
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Decatur
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Beech Grove
country: United States
facility: Novartis Investigative Site
state: Indiana
city: Witchita
country: United States
facility: Novartis Investigative Site
state: Kansas
city: Louisville
country: United States
facility: Novartis Investigative Site
state: Kentucky
city: New Orleans
country: United States
facility: Novartis Investigative Site
state: Louisiana
city: Baltimore
country: United States
facility: Novartis Investigative Site
state: Maryland
city: Boston
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Worcester
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Novartis Investigative Site
state: Michigan
city: Detroit
country: United States
facility: Novartis Investigative Site
state: Michigan
city: East Lansing
country: United States
facility: Novartis Investigative Site
state: Michigan
city: Minneapolis
country: United States
facility: Novartis Investigative Site
state: Minnesota
city: St. Louis
country: United States
facility: Novartis Investigative Site
state: Missouri
city: Billings
country: United States
facility: Novartis Investigative Site
state: Montana
city: Omaha
country: United States
facility: Novartis Investigative Site
state: Nebraska
city: Hackensack
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Alburquerque
country: United States
facility: Novartis Investigative Site
state: New Mexico
city: Alburquerque
country: United States
facility: Novartis Investigative Site
state: New Mexico
city: Farmington
country: United States
facility: Novartis Investigative Site
state: New Mexico
city: Buffalo
country: United States
facility: Novartis Investigative Site
state: New York
city: New York
country: United States
facility: Novartis Investigative Site
state: New York
city: New York
country: United States
facility: Novartis Investigative Site
state: New York
city: New York
country: United States
facility: Novartis Investigative Site
state: New York
city: Syracuse
country: United States
facility: Novartis Investigative Site
state: New York
city: Chapel Hill
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Charlotte
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Durham
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Cleveland
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Columbus
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Columbus
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Dayton
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Tulsa
country: United States
facility: Novartis Investigative Site
state: Oklahoma
city: Portland
country: United States
facility: Novartis Investigative Site
state: Oregon
city: Pittsburg
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Pittsburg
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Providence
country: United States
facility: Novartis Investigative Site
state: Rhode Island
city: Spartanburg
country: United States
facility: Novartis Investigative Site
state: South Carolina
city: Memphis
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Nashville
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Nashville
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Dallas
country: United States
facility: Novartis Investigative Site
state: Texas
city: Dallas
country: United States
facility: Novartis Investigative Site
state: Texas
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Salt Lake City
country: United States
facility: Novartis Investigative Site
state: Utah
city: Seattle
country: United States
facility: Novartis Investigative Site
state: Washington
city: Milwaukee
country: United States
facility: Novartis Investigative Site
state: Wisconsin
city: Adelaide
country: Australia
facility: Novartis Investigative Site
city: Brisbane
country: Australia
facility: Novartis Investigative Site
city: Darlinghurst
country: Australia
facility: Novartis Investigative Site
city: East Melbourne
country: Australia
facility: Novartis Investigative Site
city: Nedlands
country: Australia
facility: Novartis Investigative Site
city: Parkville
country: Australia
facility: Novartis Investigative Site
city: Prahan
country: Australia
facility: Novartis Investigative Site
city: South Brisbane
country: Australia
facility: Novartis Investigative Site
city: St. Leonards
country: Australia
facility: Novartis Investigative Site
city: Sydney
country: Australia
facility: Novartis Investigative Site
city: Westmead
country: Australia
facility: Novartis Investigative Site
city: Wien
country: Austria
facility: Novartis Investigative Site
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Godinne
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Calgary
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Edmonton
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Winnipeg
country: Canada
facility: Novartis Investigative Site
state: Manitoba
city: Halifax
country: Canada
facility: Novartis Investigative Site
state: Nova Scotia
city: Hamilton
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: London
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Ottawa
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Arhus
country: Denmark
facility: Novartis Investigative Site
city: Copenhagen
country: Denmark
facility: Novartis Investigative Site
city: Herlev
country: Denmark
facility: Novartis Investigative Site
city: Creteil
country: France
facility: Novartis Investigative Site
city: Lille
country: France
facility: Novartis Investigative Site
city: Lyon
country: France
facility: Novartis Investigative Site
city: Marseille
country: France
facility: Novartis Investigative Site
city: Nantes
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Pessac
country: France
facility: Novartis Investigative Site
city: Poitiers
country: France
facility: Novartis Investigative Site
city: Strasbourg
country: France
facility: Novartis Investigative Site
city: Vandoeuvre-les-Nancy
country: France
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Dusseldorf
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Mannheim
country: Germany
facility: Novartis Investigative Site
city: Marburg
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Munchen
country: Germany
facility: Novartis Investigative Site
city: Regensburg
country: Germany
facility: Novartis Investigative Site
city: Rostock
country: Germany
facility: Novartis Investigative Site
city: Stuttgart
country: Germany
facility: Novartis Investigative Site
city: Bari
country: Italy
facility: Novartis Investigative Site
city: Bologna
country: Italy
facility: Novartis Investigative Site
city: Firenze
country: Italy
facility: Novartis Investigative Site
city: Genova
country: Italy
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Orbassano
country: Italy
facility: Novartis Investigative Site
city: Pavia
country: Italy
facility: Novartis Investigative Site
city: Pescara
country: Italy
facility: Novartis Investigative Site
city: Pisa
country: Italy
facility: Novartis Investigative Site
city: Reggio Calabria
country: Italy
facility: Novartis Investigative Site
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Rotterdam
country: Netherlands
facility: Novartis Investigative Site
city: Auckland
country: New Zealand
facility: Novartis Investigative Site
city: Oslo
country: Norway
facility: Novartis Investigative Site
city: Tromso
country: Norway
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Salamanca
country: Spain
facility: Novartis Investigative Site
city: Valencia
country: Spain
facility: Novartis Investigative Site
city: Goteborg
country: Sweden
facility: Novartis Investigative Site
city: Linkoping
country: Sweden
facility: Novartis Investigative Site
city: Lund
country: Sweden
facility: Novartis Investigative Site
city: Orebro
country: Sweden
facility: Novartis Investigative Site
city: Stockholm
country: Sweden
facility: Novartis Investigative Site
city: Stockholm
country: Sweden
facility: Novartis Investigative Site
city: Umea
country: Sweden
facility: Novartis Investigative Site
city: Uppsala
country: Sweden
facility: Novartis Investigative Site
city: Basel
country: Switzerland
facility: Novartis Investigative Site
city: Bern
country: Switzerland
facility: Novartis Investigative Site
city: St. Gallen
country: Switzerland
facility: Novartis Investigative Site
city: Birmingham
country: United Kingdom
facility: Novartis Investigative Site
city: Cambridge
country: United Kingdom
facility: Novartis Investigative Site
city: Cardiff
country: United Kingdom
facility: Novartis Investigative Site
city: Leeds
country: United Kingdom
facility: Novartis Investigative Site
city: Liverpool
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
city: Nottingham
country: United Kingdom
facility: Novartis Investigative Site
city: Plymouth
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Hochhaus A, Larson RA, Guilhot F, Radich JP, Branford S, Hughes TP, Baccarani M, Deininger MW, Cervantes F, Fujihara S, Ortmann CE, Menssen HD, Kantarjian H, O'Brien SG, Druker BJ; IRIS Investigators. Long-Term Outcomes of Imatinib Treatment for Chronic Myeloid Leukemia. N Engl J Med. 2017 Mar 9;376(10):917-927. doi: 10.1056/NEJMoa1609324.
citation: Jain P, Kantarjian H, Nazha A, O'Brien S, Jabbour E, Romo CG, Pierce S, Cardenas-Turanzas M, Verstovsek S, Borthakur G, Ravandi F, Quintas-Cardama A, Cortes J. Early responses predict better outcomes in patients with newly diagnosed chronic myeloid leukemia: results with four tyrosine kinase inhibitor modalities. Blood. 2013 Jun 13;121(24):4867-74. doi: 10.1182/blood-2013-03-490128. Epub 2013 Apr 25.
citation: Larson RA, Druker BJ, Guilhot F, O'Brien SG, Riviere GJ, Krahnke T, Gathmann I, Wang Y; IRIS (International Randomized Interferon vs STI571) Study Group. Imatinib pharmacokinetics and its correlation with response and safety in chronic-phase chronic myeloid leukemia: a subanalysis of the IRIS study. Blood. 2008 Apr 15;111(8):4022-8. doi: 10.1182/blood-2007-10-116475. Epub 2008 Feb 6.