Clinical trial NCT00123474: Chronic Myelogenous Leukemia (CML) - Follow on: Study of BMS-354825 in Subjects With CML
Official title: A Randomized Two-by-Two, Multicenter, Open-Label Phase III Study of BMS-354825 Administered Orally at a Dose of 50 mg or 70 mg Twice Daily or 100 mg or 140 mg Once Daily in Subjects With Chronic Phase Philadelphia Chromosome or BCR-ABL Positive Chronic Myelogenous Leukemia Who Are Resistant or Intolerant to Imatinib Mesylate (Gleevec)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Myeloid Leukemia, Chronic, Chronic-Phase
Keywords: Chronic Phase Chronic Myelogenous Leukemia
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2005-07-25
Enrollment: 724
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a phase III study of BMS-354825 in subjects with chronic phase Philadelphia chromosome or BCR-ABL positive chronic myelogenous leukemia, who are resistant or intolerant to imatinib mesylate (Gleevec).


Eligibility criteria: For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

Inclusion Criteria:

* Subjects with Philadelphia chromosome positive (Ph+) (or BCR/ABL+) chronic phase chronic myeloid leukemia whose disease has primary or acquired hematologic resistance to imatinib mesylate or who are intolerant of imatinib mesylate.
* Men and women, 18 years or older
* Adequate hepatic function
* Adequate renal function
* Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for a period of at least 1 month before and at least 3 months after the study in such a manner that the risk of pregnancy is minimized.

Exclusion Criteria:

* Women who are pregnant or breastfeeding
* Subjects who are eligible and willing to undergo transplantation during the screening period
* A serious uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy
* Uncontrolled or significant cardiovascular disease
* Medications that increase bleeding risk
* Medications that change heart rhythms
* Dementia or altered mental status that would prohibit the understanding or rendering of informed consent
* History of significant bleeding disorder unrelated to CML
* Concurrent incurable malignancy other than CML
* Evidence of organ dysfunction or digestive dysfunction that would prevent administration of study therapy
* Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study

Primary outcomes:
measure: Percent of Participants With Major Cytogenetic Response (MCyR) at 6 Months Follow-Up
timeFrame: 6 months
Secondary outcomes:
measure: Percent of Participants With MCyR At or Prior to 24 Months Follow-Up
timeFrame: 24 months
measure: Percent of Participants With Complete Hematologic Response (CHR) at 6 and 24 Months Follow-Up
timeFrame: 6 months, 24 months
measure: Time to MCyR in Participants With MCyR at 6 Months Follow-Up
timeFrame: 6 months
measure: Time to CHR in Participants With CHR at 6 Months Follow-Up
timeFrame: 6 months
measure: Time to MCyR in Participants With MCyR at 24 Months Follow-Up
timeFrame: 24 months
measure: Time to CHR in Participants With CHR At 24 Months Follow-Up
timeFrame: 24 months
measure: Number of Participants With MCyR Whose Disease Progressed by 24 Months
timeFrame: 24 months
measure: Number of Participants With CHR Whose Disease Progressed by 24 Months
timeFrame: 24 months
measure: Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants
timeFrame: Baseline up to 24 months
measure: Percent of Imatinib-Resistant Participants With Progression Free Survival (PFS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up
timeFrame: 24, 36, 48, 60, 72, and 84 months
measure: Percent of Imatinib-Resistant Participants With Overall Survival (OS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up
timeFrame: 24, 36, 48, 60, 72, and 84 months
measure: Percent of Participants Intolerant to Imatinib With MCyR at 6 Months and at 24 Months Follow-Up, by QD and BID Schedules and by Total Daily Dose
timeFrame: 6 months, 24 months
measure: Percent of Participants Intolerant to Imatinib With CHR at 6 Months and at 24 Months Follow-Up
timeFrame: 6 months, 24 months
measure: Percent of Imatinib Intolerant Participants With Progression Free Survival After 24, 36, 48, 60, 72, and 84 Months of Follow-Up
timeFrame: 24, 36, 48, 60, 72, and 84 months
measure: Percent of Imatinib Intolerant Participants With Overall Survival After 24, 36, 48, 60, 72, and 84 Months of Follow-up
timeFrame: 24, 36, 48, 60, 72, and 84 months
measure: Percent of All Randomized Participants With Cytogenic and Hematologic Response by Dosing Schedule (QD or BID) and by Total Daily Dose (100 mg or 140 mg) at 6 Months Follow-Up
timeFrame: 6 months
measure: Percent of All Randomized Participants With Cytogenic and Hematologic Response by Dosing Schedule (QD or BID) and by Total Daily Dose (100 mg or 140 mg) at 24 Months Follow-Up
timeFrame: 24 months
measure: Percent of Participants With Progression Free Survival (PFS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up by Dose Schedule and Total Daily Dose - All Randomized Participants
timeFrame: 24, 36, 48, 60, 72, and 84 months
measure: Percent of Participants Overall Survival at 24, 36, 48, 60, 72, and 84 Months Follow-Up - All Randomized Participants
timeFrame: 24, 36, 48, 60, 72, and 84 months
measure: Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) That Led to Treatment Discontinuation at 24 Months of Follow-up
timeFrame: Baseline to 30 days post last dose, up to 24 months
measure: Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) That Led toTreatment Discontinuation After 7 Year Follow-up
timeFrame: Baseline to 30 days post last dose, up to 7 years (study closure July 2014)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University Of Alabama At Birmingham
state: Alabama
city: Alhambra
country: United States
facility: Central Hematology Oncology Medical Group Inc.
state: California
city: Anaheim
country: United States
facility: Pacific Cancer Medical Center Inc
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Cancer Center
state: California
city: Long Beach
country: United States
facility: Pacific Shores Medical Group
state: California
city: Los Angeles
country: United States
facility: Ucla Dept. Of Medicine
state: California
city: Oxnard
country: United States
facility: Ventura County Hematology-Oncology Specialists
state: California
city: Vallejo
country: United States
facility: Kaiser Permanente Medical Center
state: California
city: Washington
country: United States
facility: Georgetown University Med Ctr
state: District of Columbia
city: Washington
country: United States
facility: Washington Cancer Institute At Washington Hospital Center
state: District of Columbia
city: Gainesville
country: United States
facility: University Of Florida
state: Florida
city: Miami
country: United States
facility: University Of Miami
state: Florida
city: Orlando
country: United States
facility: Md Anderson Cancer Center Orlando
state: Florida
city: Atlanta
country: United States
facility: Emory University School Of Medicine
state: Georgia
city: Atlanta
country: United States
facility: Georgia Cancer Specialists
state: Georgia
city: Lawrenceville
country: United States
facility: Gwinnett Hospital System Inc.
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Feinberg School Of Medicine
state: Illinois
city: Chicago
country: United States
facility: University Of Chicago
state: Illinois
city: Peoria
country: United States
facility: Oncology Hematology Associates Of Central Illinois, Pc
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Westwood
country: United States
facility: University Of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: University Of Kentucky
state: Kentucky
city: Baltimore
country: United States
facility: University Of Maryland
state: Maryland
city: Boston
country: United States
facility: Dana Faber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School Of Medicine
state: Missouri
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Omaha
country: United States
facility: Devetten, Marcel
state: Nebraska
city: Las Vegas
country: United States
facility: Nevada Cancer Institute
state: Nevada
city: Hackensack
country: United States
facility: The Cancer Center At Hackensack University Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: The Cancer Institute Of New Jersey
state: New Jersey
city: New York
country: United States
facility: New York Presbyterian Hospital
state: New York
city: Chapel Hill
country: United States
facility: University Of North Carolina At Chapel Hill
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Pittsburgh
country: United States
facility: Western Pennsylvania Cancer Institute
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Dallas
country: United States
facility: Ut Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: The University Of Texas Md Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: La Plata
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Capital Federal
country: Argentina
facility: Local Institution
city: Cordoba
country: Argentina
facility: Local Institution
city: Camperdown
country: Australia
facility: Local Institution
state: New South Wales
city: St Leonards
country: Australia
facility: Local Institution
state: New South Wales
city: South Brisbane
country: Australia
facility: Local Institution
state: Queensland
city: Adelaide
country: Australia
facility: Local Institution
state: South Australia
city: East Melbourne
country: Australia
facility: Local Institution
state: Victoria
city: Perth
country: Australia
facility: Local Institution
state: Western Australia
city: Wien
country: Austria
facility: Local Institution
city: B-leuven
country: Belgium
facility: Local Institution
city: Brugge
country: Belgium
facility: Local Institution
city: Bruxelles
country: Belgium
facility: Local Institution
city: Charleroi
country: Belgium
facility: Local Institution
city: Edegem
country: Belgium
facility: Local Institution
city: Yvoir
country: Belgium
facility: Local Institution
city: Curitiba
country: Brazil
facility: Local Institution
state: Parana
city: CEP - Campinas
country: Brazil
facility: Local Institution
city: Rio de Janeiro
country: Brazil
facility: Local Institution
city: San Paulo, Sp
country: Brazil
facility: Local Institution
city: Sao Paulo
country: Brazil
facility: Local Institution
city: Edmonton
country: Canada
facility: Local Institution
state: Alberta
city: Hamilton
country: Canada
facility: Local Institution
state: Ontario
city: Montreal
country: Canada
facility: Local Institution
state: Quebec
city: Brno
country: Czech Republic
facility: Local Institution
city: Prague 2
country: Czech Republic
facility: Local Institution
city: Aarhus C
country: Denmark
facility: Local Institution
city: Herlev
country: Denmark
facility: Local Institution
city: Odense C
country: Denmark
facility: Local Institution
city: Helsinki
country: Finland
facility: Local Institution
city: Cedex
country: France
facility: Local Institution
state: Pierre Benite
city: Caen
country: France
facility: Local Institution
city: Creteil Cedex
country: France
facility: Local Institution
city: Grenoble Cedex 09
country: France
facility: Local Institution
city: Lille Cedex
country: France
facility: Local Institution
city: Marseille Cedex 9
country: France
facility: Local Institution
city: Nantes
country: France
facility: Local Institution
city: Paris Cedex 10
country: France
facility: Local Institution
city: Poitiers Cedex
country: France
facility: Local Institution
city: Strasbourg
country: France
facility: Local Institution
city: Toulouse Cedex 9
country: France
facility: Local Institution
city: Dresden
country: Germany
facility: Local Institution
city: Frankfurt/main
country: Germany
facility: Local Institution
city: Hamburg
country: Germany
facility: Local Institution
city: Leipzig
country: Germany
facility: Local Institution
city: Mainz
country: Germany
facility: Local Institution
city: Mannheim
country: Germany
facility: Local Institution
city: Budapest
country: Hungary
facility: Local Institution
city: Co Galway
country: Ireland
facility: Local Institution
state: Galway
city: Dublin
country: Ireland
facility: Local Institution
city: Ramat-gan
country: Israel
facility: Local Institution
city: Bari
country: Italy
facility: Local Institution
city: Monza (mi)
country: Italy
facility: Local Institution
city: Napoli
country: Italy
facility: Local Institution
city: Orbassano
country: Italy
facility: Local Institution
city: Roma
country: Italy
facility: Local Institution
city: Roma
country: Italy
facility: Local Institution
city: Jeollanam-do
country: Korea, Republic of
facility: Local Institution
city: Kyunggi-do
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Distrito Federal
country: Mexico
facility: Local Institution
city: Nijmegen
country: Netherlands
facility: Local Institution
city: Rotterdam
country: Netherlands
facility: Local Institution
city: Trondheim
country: Norway
facility: Local Institution
city: Jesus Maria
country: Peru
facility: Local Institution
state: Lima
city: Lima
country: Peru
facility: Local Institution
city: Quezon City
country: Philippines
facility: Local Institution
city: Gdansk
country: Poland
facility: Local Institution
city: Katowice
country: Poland
facility: Local Institution
city: Krakow
country: Poland
facility: Local Institution
city: Lodz
country: Poland
facility: Local Institution
city: Lublin
country: Poland
facility: Local Institution
city: Warsaw
country: Poland
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: St.petersburg
country: Russian Federation
facility: Local Institution
city: Singapore
country: Singapore
facility: Local Institution
city: Bloemfontein
country: South Africa
facility: Local Institution
state: Free State
city: Groenkloof
country: South Africa
facility: Local Institution
state: Gauteng
city: Parktown
country: South Africa
facility: Local Institution
state: Gauteng
city: Soweto
country: South Africa
facility: Local Institution
state: Gauteng
city: Observatory
country: South Africa
facility: Local Institution
state: Western Cape
city: Madrid
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Pamplona
country: Spain
facility: Local Institution
city: Lund
country: Sweden
facility: Local Institution
city: Uppsala
country: Sweden
facility: Local Institution
city: Basel
country: Switzerland
facility: Local Institution
city: Taipei
country: Taiwan
facility: Local Institution
city: Taoyuan County
country: Taiwan
facility: Local Institution
city: Cambridge
country: United Kingdom
facility: Local Institution
state: Cambridgeshire
city: London
country: United Kingdom
facility: Local Institution
state: Greater London
city: Liverpool
country: United Kingdom
facility: Local Institution
state: Merseyside
city: Newcastle
country: United Kingdom
facility: Local Institution
state: Tyne And Wear
city: Birmingham
country: United Kingdom
facility: Local Institution
state: West Midlands
city: Glasgow
country: United Kingdom
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Porkka K, Khoury HJ, Paquette RL, Matloub Y, Sinha R, Cortes JE. Dasatinib 100 mg once daily minimizes the occurrence of pleural effusion in patients with chronic myeloid leukemia in chronic phase and efficacy is unaffected in patients who develop pleural effusion. Cancer. 2010 Jan 15;116(2):377-86. doi: 10.1002/cncr.24734.
citation: Muller MC, Cortes JE, Kim DW, Druker BJ, Erben P, Pasquini R, Branford S, Hughes TP, Radich JP, Ploughman L, Mukhopadhyay J, Hochhaus A. Dasatinib treatment of chronic-phase chronic myeloid leukemia: analysis of responses according to preexisting BCR-ABL mutations. Blood. 2009 Dec 3;114(24):4944-53. doi: 10.1182/blood-2009-04-214221. Epub 2009 Sep 24.
citation: Shah NP, Kantarjian HM, Kim DW, Rea D, Dorlhiac-Llacer PE, Milone JH, Vela-Ojeda J, Silver RT, Khoury HJ, Charbonnier A, Khoroshko N, Paquette RL, Deininger M, Collins RH, Otero I, Hughes T, Bleickardt E, Strauss L, Francis S, Hochhaus A. Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and -intolerant chronic-phase chronic myeloid leukemia. J Clin Oncol. 2008 Jul 1;26(19):3204-12. doi: 10.1200/JCO.2007.14.9260. Epub 2008 Jun 9.
citation: Shah NP, Rousselot P, Schiffer C, Rea D, Cortes JE, Milone J, Mohamed H, Healey D, Kantarjian H, Hochhaus A, Saglio G. Dasatinib in imatinib-resistant or -intolerant chronic-phase, chronic myeloid leukemia patients: 7-year follow-up of study CA180-034. Am J Hematol. 2016 Sep;91(9):869-74. doi: 10.1002/ajh.24423. Epub 2016 Jun 20.
citation: Shah NP, Guilhot F, Cortes JE, Schiffer CA, le Coutre P, Brummendorf TH, Kantarjian HM, Hochhaus A, Rousselot P, Mohamed H, Healey D, Cunningham M, Saglio G. Long-term outcome with dasatinib after imatinib failure in chronic-phase chronic myeloid leukemia: follow-up of a phase 3 study. Blood. 2014 Apr 10;123(15):2317-24. doi: 10.1182/blood-2013-10-532341. Epub 2014 Feb 25.