Clinical trial NCT00519090: Nilotinib vs Imatinib in Adult Patients With Philadelphia (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)
Official title: A Phase III Randomized, Open- Label Multi-center Study of Nilotinib Versus Imatinib in Adult Patients With Ph+ Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) Who Have a Suboptimal Cytogenetic Response (CyR) on Imatinib
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Myelogenous Leukemia
Keywords: leukemia
bone marrow
leukemia symptoms
cml
complete blood count
lymphocyte
blood cancer
leukocytes
chronic leukemia
bone marrow biopsy
leukemia research
leukemia cells
bone marrow disease
chronic myeloid leukemia
blood cancer symptoms
white blood cell diseases
chronic myelogenous leukemia
leukemia treatment
leukemia facts
leucemia
facts about leukemia
myelogenous leukemia
newly diagnosed CML
suboptimal response
Philadelphia chromosome positive (Ph+)
chronic myelogenous leukemia in chronic phase (CML-CP)
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2007-08-21
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In this study, the efficacy and safety of nilotinib 400 mg twice daily, will be compared with imatinib 400 mg twice daily in patients with a suboptimal response to imatinib for their Philadelphia chromosome-positive (Ph+) Chronic Myelogenous Leukemia in the chronic phase (CML-CP).

Detailed description: This trial was to evaluate the CCyR rate at 12 months of nilotinib therapy when compared to imatinib treatment in patients with suboptimal response to imatinib. The patients were stratified by prior duration of initial imatinib treatment, and were randomized to receive either 400 mg/twice daily of continuous nilotinib or imatinib treatment. The first stratum patients were treated with imatinib = 6 to \< 12 months and having at least a minimal cytogenetic, but no partial cytogenetic response; and the second stratum patients were treated with imatinib = 12 months to \< 18 months and having partial cytogenetic response (PCyR), but no CCyR.

Eligibility criteria: Inclusion criteria:

Diagnosis of Philadelphia chromosome positive chronic myelogenous leukemia in the chronic phase.

Patients with suboptimal cytogenetic response to a dose of 400 mg imatinib (first line therapy) defined as:

* 6 to \< 12 months of treatment and -have 36 - 95% Ph+ metaphases, or
* 12 to \<18 months of treatment and have 1 - 35% Ph+ metaphases (Standard cytogenetics, no FISH \[fluorescence in situ hybridization\] analysis was allowed).

Exclusion criteria:

* Patient who have received more than 18 months of imatinib therapy
* Patients who have achieved partial or complete cytogenetic response and lost that response prior to entering the study.
* Prior treatment with greater than 400 mg/day imatinib.
* Uncontrolled or significant cardiovascular disease.
* Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection).
* Use of therapeutic coumarin derivatives (i.e., warfarin, acenocoumarol, phenprocoumon)
* Currently taking certain medications that could affect the rhythm of your heart.

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Complete Cytogenetic Response Rate(CCyR) in Patients Who Had a Suboptimal Cytogenetic Response on Imatinib
timeFrame: 12 months
Secondary outcomes:
measure: Durable Complete Cytogenetic Response Rate
timeFrame: 24 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Cancer Center
state: Arizona
city: Anaheim
country: United States
facility: Southern California Permanente Medical Group
state: California
city: Baldwin Park
country: United States
facility: Southern California Permanente Medical Group
state: California
city: Fontana
country: United States
facility: Southern California Permanente Medical Group
state: California
city: Hayward
country: United States
facility: Kaiser Permanente Medical Group/Hayward Medical Center
state: California
city: Los Angeles
country: United States
facility: Southern California Permanente Medical Group
state: California
city: Oakland
country: United States
facility: Kaiser Permanente Medical Group/Oakland Medical Center
state: California
city: Panorama City
country: United States
facility: Southern California Permanente Medical Group
state: California
city: Riverside
country: United States
facility: Southern California Permanente Medical Group
state: California
city: S. San Francisco
country: United States
facility: Kaiser Permanente Medical Group/South San Francisco Medical Center
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente Medical Group/Sacramento Medical Center
state: California
city: San Diego
country: United States
facility: Southern California Permanente Medical Group
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente Medical Group
state: California
city: San Jose
country: United States
facility: Kaiser Permanente Medical Group
state: California
city: Santa Clara
country: United States
facility: Kaiser Permanente Medical Group/Santa Clara Medical Office
state: California
city: Vallejo
country: United States
facility: Kaiser Permanente Medical Group/Vallejo Medical Center
state: California
city: Walnut Creek
country: United States
facility: Kaiser Permanente Medical Group/Walnut Creek Medical Center
state: California
city: Woodland Hills
country: United States
facility: Southen California Permanente Medical Group
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: The University of Chicago Medical Center
state: Illinois
city: Beech Grove
country: United States
facility: Indiana Blood and Marrow Transplantation
state: Indiana
city: Iowa City
country: United States
facility: Holden Cancer Center
state: Iowa
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Grand Rapids
country: United States
facility: Hematology Centers of Western Michigan
state: Michigan
city: Omaha
country: United States
facility: Methodist Cancer Center
state: Nebraska
city: Hackensack
country: United States
facility: The Cancer Center at Hackensack University Medical Center
state: New Jersey
city: Durham
country: United States
facility: Duke University Hospital
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Bethlehem
country: United States
facility: St. Luke's Hospital and Health Network
state: Pennsylvania
city: Germantown
country: United States
facility: Jones Cancer Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Houston
country: United States
facility: University of Texas/MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Darlinghurst
country: Australia
facility: Novartis Investigative Site
city: Herston
country: Australia
facility: Novartis Investigative Site
city: Liverpool
country: Australia
facility: Novartis Investigative Site
city: Perth
country: Australia
facility: Novartis Investigative Site
city: Prahran
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: Brugge
country: Belgium
facility: Novartis Investigative Site
city: Gent
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Mannheim
country: Brazil
facility: Novartis Investigative Site
city: Porto Alegre
country: Brazil
facility: Novartis Investigative Site
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
city: Olomouc
country: Czech Republic
facility: Novartis Investigative Site
city: Praha
country: Czech Republic
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Duesseldorf
country: Germany
facility: Novartis Investigative Site
city: Eisensach
country: Germany
facility: Novartis Investigative Site
city: Firenze
country: Germany
facility: Novartis Investigative Site
city: Griefswald
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Jena
country: Germany
facility: Novartis Investigative Site
city: Kiel
country: Germany
facility: Novartis Investigative Site
city: Leipzeg
country: Germany
facility: Novartis Investigative Site
city: Postsdam
country: Germany
facility: Novartis Investigative Site
city: Rostock
country: Germany
facility: Novartis Investigative Site
city: Stuttgart
country: Germany
facility: Novartis Investigative Site
city: Weiden
country: Germany
facility: Novartis Investigative Site
city: Bologna
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: Reggio Calabra
country: Italy
facility: Novartis Investigative Site
city: Roma
country: Italy
facility: Novartis Investigative Site
city: Nagoya
country: Japan
facility: Novartis Investigative Site
city: Oaska
country: Japan
facility: Novartis Investigative Site
city: Tokyo
country: Japan
facility: Novartis Investigative Site
city: Hwasun-Gun
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Salamanca
country: Spain
facility: Novartis Investigative Site
city: Santiago de Compostela
country: Spain
facility: Novartis Investigative Site
city: Valencia
country: Spain
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Agrawal M, Hanfstein B, Erben P, Wolf D, Ernst T, Fabarius A, Saussele S, Purkayastha D, Woodman RC, Hofmann WK, Hehlmann R, Hochhaus A, Muller MC. MDR1 expression predicts outcome of Ph+ chronic phase CML patients on second-line nilotinib therapy after imatinib failure. Leukemia. 2014 Jul;28(7):1478-85. doi: 10.1038/leu.2014.6. Epub 2014 Jan 10.