Chronic Myelogenous Leukemia (CML) - Follow on: Study of BMS-354825 in Subjects With CML

Myeloid Leukemia, Chronic, Chronic-Phase Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00123474
• Other study ID #: CA180-034
• Status: Completed
• Phase: Phase 3
• First received: July 21, 2005
• Last updated: July 29, 2015
• Start date: July 2005
• Est. completion date: July 2014

Study information

• Verified date: July 2015
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 724
• Est. completion date: July 2014
• Est. primary completion date: September 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 90 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Chronic-Phase
• Myeloid Leukemia, Chronic, Chronic-Phase

Intervention

Drug:
• dasatinib
Tablets, Oral, 50 mg BID, indefinitely, survival study
• dasatinib
Tablets, Oral, 70 mg BID, indefinitely, survival study
• dasatinib
Tablets, Oral, 100 mg QD, indefinitely, survival study
• dasatinib
Tablets, Oral, 140 mg QD, indefinitely, survival study

Locations

Country	Name	City	State
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Capital Federal
Argentina	Local Institution	Cordoba
Argentina	Local Institution	La Plata	Buenos Aires
Australia	Local Institution	Adelaide	South Australia
Australia	Local Institution	Camperdown	New South Wales
Australia	Local Institution	East Melbourne	Victoria
Australia	Local Institution	Perth	Western Australia
Australia	Local Institution	South Brisbane	Queensland
Australia	Local Institution	St Leonards	New South Wales
Austria	Local Institution	Wien
Belgium	Local Institution	B-leuven
Belgium	Local Institution	Brugge
Belgium	Local Institution	Bruxelles
Belgium	Local Institution	Charleroi
Belgium	Local Institution	Edegem
Belgium	Local Institution	Yvoir
Brazil	Local Institution	CEP - Campinas
Brazil	Local Institution	Curitiba	Parana
Brazil	Local Institution	Rio de Janeiro
Brazil	Local Institution	San Paulo, Sp
Brazil	Local Institution	Sao Paulo
Canada	Local Institution	Edmonton	Alberta
Canada	Local Institution	Hamilton	Ontario
Canada	Local Institution	Montreal	Quebec
Czech Republic	Local Institution	Brno
Czech Republic	Local Institution	Prague 2
Denmark	Local Institution	Aarhus C
Denmark	Local Institution	Herlev
Denmark	Local Institution	Odense C
Finland	Local Institution	Helsinki
France	Local Institution	Caen
France	Local Institution	Cedex	Pierre Benite
France	Local Institution	Creteil Cedex
France	Local Institution	Grenoble Cedex 09
France	Local Institution	Lille Cedex
France	Local Institution	Marseille Cedex 9
France	Local Institution	Nantes
France	Local Institution	Paris Cedex 10
France	Local Institution	Poitiers Cedex
France	Local Institution	Strasbourg
France	Local Institution	Toulouse Cedex 9
Germany	Local Institution	Dresden
Germany	Local Institution	Frankfurt/main
Germany	Local Institution	Hamburg
Germany	Local Institution	Leipzig
Germany	Local Institution	Mainz
Germany	Local Institution	Mannheim
Hungary	Local Institution	Budapest
Ireland	Local Institution	Co Galway	Galway
Ireland	Local Institution	Dublin
Israel	Local Institution	Ramat-gan
Italy	Local Institution	Bari
Italy	Local Institution	Monza (mi)
Italy	Local Institution	Napoli
Italy	Local Institution	Orbassano
Italy	Local Institution	Roma
Italy	Local Institution	Roma
Korea, Republic of	Local Institution	Jeollanam-do
Korea, Republic of	Local Institution	Kyunggi-do
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Mexico	Local Institution	Distrito Federal
Netherlands	Local Institution	Nijmegen
Netherlands	Local Institution	Rotterdam
Norway	Local Institution	Trondheim
Peru	Local Institution	Jesus Maria	Lima
Peru	Local Institution	Lima
Philippines	Local Institution	Quezon City
Poland	Local Institution	Gdansk
Poland	Local Institution	Katowice
Poland	Local Institution	Krakow
Poland	Local Institution	Lodz
Poland	Local Institution	Lublin
Poland	Local Institution	Warsaw
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	St.petersburg
Singapore	Local Institution	Singapore
South Africa	Local Institution	Bloemfontein	Free State
South Africa	Local Institution	Groenkloof	Gauteng
South Africa	Local Institution	Observatory	Western Cape
South Africa	Local Institution	Parktown	Gauteng
South Africa	Local Institution	Soweto	Gauteng
Spain	Local Institution	Madrid
Spain	Local Institution	Madrid
Spain	Local Institution	Pamplona
Sweden	Local Institution	Lund
Sweden	Local Institution	Uppsala
Switzerland	Local Institution	Basel
Taiwan	Local Institution	Taipei
Taiwan	Local Institution	Taoyuan County
United Kingdom	Local Institution	Birmingham	West Midlands
United Kingdom	Local Institution	Cambridge	Cambridgeshire
United Kingdom	Local Institution	Glasgow
United Kingdom	Local Institution	Liverpool	Merseyside
United Kingdom	Local Institution	London	Greater London
United Kingdom	Local Institution	Newcastle	Tyne And Wear
United States	Central Hematology Oncology Medical Group Inc.	Alhambra	California
United States	Pacific Cancer Medical Center Inc	Anaheim	California
United States	Emory University School Of Medicine	Atlanta	Georgia
United States	Georgia Cancer Specialists	Atlanta	Georgia
United States	University Of Maryland	Baltimore	Maryland
United States	University Of Alabama At Birmingham	Birmingham	Alabama
United States	Dana Faber Cancer Institute	Boston	Massachusetts
United States	University Of North Carolina At Chapel Hill	Chapel Hill	North Carolina
United States	Northwestern University Feinberg School Of Medicine	Chicago	Illinois
United States	University Of Chicago	Chicago	Illinois
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Ut Southwestern Medical Center	Dallas	Texas
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	University Of Florida	Gainesville	Florida
United States	The Cancer Center At Hackensack University Medical Center	Hackensack	New Jersey
United States	The University Of Texas Md Anderson Cancer Center	Houston	Texas
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	Nevada Cancer Institute	Las Vegas	Nevada
United States	Gwinnett Hospital System Inc.	Lawrenceville	Georgia
United States	University Of Kentucky	Lexington	Kentucky
United States	Loma Linda University Cancer Center	Loma Linda	California
United States	Pacific Shores Medical Group	Long Beach	California
United States	Ucla Dept. Of Medicine	Los Angeles	California
United States	University Of Miami	Miami	Florida
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	The Cancer Institute Of New Jersey	New Brunswick	New Jersey
United States	New York Presbyterian Hospital	New York	New York
United States	Devetten, Marcel	Omaha	Nebraska
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	Md Anderson Cancer Center Orlando	Orlando	Florida
United States	Ventura County Hematology-Oncology Specialists	Oxnard	California
United States	Oncology Hematology Associates Of Central Illinois, Pc	Peoria	Illinois
United States	Western Pennsylvania Cancer Institute	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	Washington University School Of Medicine	Saint Louis	Missouri
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Kaiser Permanente Medical Center	Vallejo	California
United States	Georgetown University Med Ctr	Washington	District of Columbia
United States	Washington Cancer Institute At Washington Hospital Center	Washington	District of Columbia
United States	University Of Kansas Medical Center	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Czech Republic,  Denmark,  Finland,  France,  Germany,  Hungary,  Ireland,  Israel,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Norway,  Peru,  Philippines,  Poland,  Russian Federation,  Singapore,  South Africa,  Spain,  Sweden,  Switzerland,  Taiwan,  United Kingdom, 

References & Publications (3)

Müller 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. — View 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. — View Citation

Shah NP, Kantarjian HM, Kim DW, Réa 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent of Participants With Major Cytogenetic Response (MCyR) After at Least 6 Months Follow-Up	Cytogenetic response (CyR) was based on the number of Philadelphia chromosome positive (Ph+) metaphases among cells in metaphase on a Bone Marrow (BM) sample. The criteria for CyR were as follows: Complete cytogenetic response (CCyR): 0% Ph+ cells in metaphase in BM; Partial cytogenetic response (PCyR): >0 to 35% Ph+ cells in metaphase in BM; Minor cytogenetic response: >35 to 65% Ph+ cells in metaphase in BM; Minimal cytogenetic response: >65 to 95% Ph+ cells in metaphase in BM; No cytogenetic response: >95 to 100% Ph+ cells in metaphase in BM; Best CyR was defined as the best response obtained at any time during the study; MCyR was defined as a best CyR of complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR). Baseline=closest to, but no later than, the first day of study drug for treated participants and closest to, but no later than, the date of randomization, for those who were randomized but who never received treatment, unless otherwise specified.	Baseline and after at least 6 months follow-up	No
Secondary	Percent of Participants With MCyR At or Prior to 24 Months Follow-Up	CyR was based on the number of Ph+ metaphases among cells in metaphase on a Bone Marrow (BM) sample. The criteria for CyR were as follows: CCyR: 0% Ph+ cells in metaphase in BM; PCyR: >0 to 35% Ph+ cells in metaphase in BM; Minor cytogenetic response: >35 to 65% Ph+ cells in metaphase in BM; Minimal cytogenetic response: >65 to 95% Ph+ cells in metaphase in BM; No cytogenetic response: >95 to 100% Ph+ cells in metaphase in BM; Best CyR was defined as the best response obtained at any time during the study; MCyR was defined as a best CyR of CCyR or PCyR. Baseline=closest to, but no later than, the first day of study drug for treated participants and closest to, but no later than, the date of randomization, for those who were randomized but who never received treatment, unless otherwise specified.	Baseline and after at least 24 months follow-up	No
Secondary	Percent of Participants With Complete Hematologic Response (CHR) After at Least 6 and 24 Months Follow-Up	A complete hematologic response (CHR) was obtained when all the following criteria were met: White Blood Cells (WBC) = institutional upper limit of normal (ULN); Platelets < 450,000/mm³; No blasts or promyelocytes in peripheral blood (PB); < 5% myelocytes plus metamyelocytes in PB; Basophils in PB < 20%; No extramedullary involvement (including no splenomegaly or hepatomegaly). Hematologic responses were counted anytime following 14 days after the dosing start date.	Baseline and after at least 6 and 24 months follow-up	No
Secondary	Time to MCyR in Participants With MCyR After At Least 6 Months Follow-Up	Time to MCyR was defined as the time from the first dosing date until criteria were first met for CCyR or PCyR, whichever occurred first. Non-responders were censored at the maximum time of all participants in their respective group (ie, maximum between time to MCyR response for responders and time to last cytogenetic assessment for non-responders).	Baseline and after at least 6 months follow-up	No
Secondary	Time to CHR in Participants With CHR After at Least 6 Months Follow-Up	Time to CHR was defined as the time from the first dosing date until criteria are first met for the response. Non-responders were censored at the maximum time of all participants in their respective group (ie, maximum between time to CHR response for responders and time to last hematologic assessment for non-responders).	Baseline and after at least 6 months follow-up	No
Secondary	Time to MCyR in Participants With MCyR After at Least 24 Months Follow-Up	Time to MCyR was defined as the time from the first dosing date until criteria were first met for CCyR or PCyR, whichever occurred first. Non-responders were censored at the maximum time of all participants in their respective group (ie, maximum between time to MCyR response for responders and time to last cytogenetic assessment for non-responders). Cytogenetic assessments were not done after the 2 Year Follow-up.	Baseline and after at least 24 months follow-up	No
Secondary	Time to CHR in Participants With CHR After at Least 24 Months Follow-Up	Time to CHR was defined as the time from the first dosing date until criteria are first met for the response. Non-responders were censored at the maximum time of all participants in their respective group (ie, maximum between time to CHR response for responders and time to last hematologic assessment for non-responders). Cytogenetic assessments were not done after the 2 Year Follow-up.	Baseline and after at least 24 months follow-up	No
Secondary	Number of Participants With MCyR Whose Disease Progressed	Progression in a participant=participant achieved a CHR and no longer met the criteria consistently over consecutive 2-weeks after starting their maximum dose; had no CHR after receiving their maximum dose and had an increase in white blood count (WBC) defined as a doubling of the count from the lowest value to >20,000/mm^3 or an increase by > 50,000/mm^3 on two assessments performed at least 2 weeks apart; participant met criteria of accelerated or blast phase CML at any time; had a MCyR and subsequently no longer met the criteria for MCyR after starting their maximum dose; had a = 30% absolute increase in the number of Ph+ metaphases. Although a related secondary endpoint was estimated duration of MCyR, medium duration of MCyR could not be estimated because the majority of participants with MCyR continued to respond, or could not be reliably estimated because of the large number of censored participants. Cytogenetic assessments were not done after the 24 month follow-up.	Baseline and after at least 24 months follow-up	No
Secondary	Number of Participants With CHR Whose Disease Progressed	Progression in a participant=achieved a CHR and subsequently no longer met the criteria consistently over a consecutive 2-week period after starting their maximum dose; had no CHR after receiving their maximum dose and had an increase in white blood count (WBC) defined as a doubling of the count from the lowest value to >20,000/mm^3 or an increase by > 50,000/mm^3 on two assessments performed at least 2 weeks apart; met the criteria of accelerated or blast phase CML at any time; had a MCyR and subsequently no longer met the criteria for MCyR after starting their maximum dose; had a = 30% absolute increase in the number of Ph+ metaphases. Although a related secondary endpoint was estimated duration of CHR, medium duration of CHR could not be estimated because the majority of participants with CHR continued to respond, or could not be reliably estimated because of the large number of censored participants.	Baseline and after at least 24 months follow-up	No
Secondary	Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants	BCR-ABL mutations were assessed in participants prior to the start of study drug (baseline) and at the time of disease progression or at end of therapy. Quantification of BCR-ABL transcripts in peripheral blood was evaluated using quantitative reverse transcriptase polymerase chain reaction (Q-RT-PCR, RT-PCR).	Baseline to Year 2	No
Secondary	Percent of Imatinib-Resistant Participants With Progression Free Survival (PFS) After at Least 24, 36, 48, 60, 72, and 84 Months Follow-Up	PFS= time from randomization until: CHR achieved and participant subsequently no longer met criteria for CHR over 2 weeks; no CHR after receiving maximum dose and an increase in WBC (ie, doubling of the count from the lowest value to > 20,000/mm^3 or an increase by > 50,000/mm^3 on 2 assessments performed 2 weeks apart); participant met criteria of accelerated phase or blast phase CML; participant had MCyR and subsequently no longer met criteria for MCyR after starting maximum dose; participant had a = 30% absolute increase in number of Ph+ metaphases. Deaths without a reported prior progression were considered to have progressed on the date of death; those who neither progressed nor died were censored on the date of their last cytogenetic or hematologic assessment. When first progression reported during follow-up, it was censored at last on-study assessment. If the first progression reported during follow-up was death, participant considered to have progressed at date of death.	Baseline and after 84 months follow-up	No
Secondary	Percent of Imatinib-Resistant Participants With Overall Survival (OS) After at Least 24, 36, 48, 60, 72, and 84 Months Follow-Up	Overall survival (OS) was defined as the time from randomization until death. Survival data were collected for up to 5 years on participants who had discontinued dasatinib treatment. Participants who did not die or who were lost to follow-up were censored on the last date the participant was known to be alive.	Baseline and after 84 months follow-up	No
Secondary	Percent of Participants Intolerant to Imatinib With MCyR After at Least 6 Months and After at Least 24 Months Follow-Up, by QD and BID Schedules and by Total Daily Dose	CyR was based on the number of Ph+ metaphases among cells in metaphase on a BM sample. The criteria for CyR were as follows: complete cytogenetic response (CCyR): 0% Ph+ cells in metaphase in BM; PCyR: >0 to 35% Ph+ cells in metaphase in BM; Minor cytogenetic response: >35 to 65% Ph+ cells in metaphase in BM; Minimal cytogenetic response: >65 to 95% Ph+ cells in metaphase in BM; No cytogenetic response: >95 to 100% Ph+ cells in metaphase in BM; Best CyR was defined as the best response obtained at any time during the study; MCyR was defined as a best CyR of CCyR or PCyR.	Baseline and after at Least 6 Months and 24 Months Follow-Up	No
Secondary	Percent of Participants Intolerant to Imatinib With CHR After at Least 6 Months and After at Least 24 Months Follow-Up	A CHR was obtained when all the following criteria were met: White Blood Cells (WBC) = institutional upper limit of normal (ULN); Platelets < 450,000/mm³; No blasts or promyelocytes in peripheral blood (PB); < 5% myelocytes plus metamyelocytes in PB; Basophils in PB < 20%; No extramedullary involvement (including no splenomegaly or hepatomegaly). Hematologic responses were counted anytime following 14 days after the dosing start date.	Baseline and after at Least 6 Months and 24 Months Follow Up	No
Secondary	Percent of Imatinib Intolerant Participants With Progression Free Survival After 24, 36, 48, 60, 72, and 84 Months of Follow-Up	PFS= time from randomization until: CHR achieved and participant subsequently no longer met criteria for CHR over 2 weeks; no CHR after receiving maximum dose and an increase in WBC (ie, doubling of the count from the lowest value to > 20,000/mm^3 or an increase by > 50,000/mm^3 on 2 assessments performed 2 weeks apart); participant met criteria of accelerated phase or blast phase CML; participant had MCyR and subsequently no longer met criteria for MCyR after starting maximum dose; participant had a = 30% absolute increase in number of Ph+ metaphases. Deaths without a reported prior progression were considered to have progressed on the date of death; those who neither progressed nor died were censored on the date of their last cytogenetic or hematologic assessment. When first progression reported during follow-up, it was censored at last on-study assessment. If the first progression reported during follow-up was death, participant considered to have progressed at date of death.	Baseline and after 84 months follow-up	No
Secondary	Percent of Imatinib Intolerant Participants With Overall Survival After 24, 36, 48, 60, 72, and 84 Months of Follow-up	Overall survival (OS) was defined as the time from randomization until death. Survival data were collected for up to 5 years on participants who had discontinued dasatinib treatment. Participants who did not die or who were lost to follow-up were censored on the last date the participant was known to be alive.	Baseline and after 84 months follow-up	No
Secondary	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) After at Least 6 Months Follow-Up	Complete cytogenetic response (CCyR): 0% Ph+ cells in metaphase in BM. Partial cytogenetic response (PCyR): >0 to 35% Ph+ cells in metaphase in BM. MCyR: best cytogenetic response of CCyR or PCyR. A complete hematologic response (CHR) was obtained when all the following criteria were met: White Blood Cells (WBC) = institutional upper limit of normal (ULN); Platelets < 450,000/mm³; No blasts or promyelocytes in peripheral blood (PB); < 5% myelocytes plus metamyelocytes in PB; Basophils in PB < 20%; No extramedullary involvement (including no splenomegaly or hepatomegaly). Hematologic responses were counted anytime following 14 days after the dosing start date.	Baseline and after at least 6 months follow-up	No
Secondary	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) After at Least 24 Months Follow-Up	Complete cytogenetic response (CCyR): 0% Ph+ cells in metaphase in BM. Partial cytogenetic response (PCyR): >0 to 35% Ph+ cells in metaphase in BM. MCyR: best cytogenetic response of CCyR or PCyR. A complete hematologic response (CHR) was obtained when all the following criteria were met: White Blood Cells (WBC) = institutional upper limit of normal (ULN); Platelets < 450,000/mm³; No blasts or promyelocytes in peripheral blood (PB); < 5% myelocytes plus metamyelocytes in PB; Basophils in PB < 20%; No extramedullary involvement (including no splenomegaly or hepatomegaly). Hematologic responses were counted anytime following 14 days after the dosing start date. No cytogenic assessments were made after 2 years of follow-up.	Baseline and after at least 24 months follow-up	No
Secondary	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	PFS= time from randomization until: CHR achieved and participant subsequently no longer met criteria for CHR over 2 weeks; no CHR after receiving maximum dose and an increase in WBC (ie, doubling of the count from the lowest value to > 20,000/mm^3 or an increase by > 50,000/mm^3 on 2 assessments performed 2 weeks apart); participant met criteria of accelerated phase or blast phase CML; participant had MCyR and subsequently no longer met criteria for MCyR after starting maximum dose; participant had a = 30% absolute increase in number of Ph+ metaphases. Deaths without a reported prior progression were considered to have progressed on the date of death; those who neither progressed nor died were censored on the date of their last cytogenetic or hematologic assessment. When first progression reported during follow-up, it was censored at last on-study assessment. If the first progression reported during follow-up was death, participant considered to have progressed at date of death.	Baseline and after 84 Months Follow-up	No
Secondary	Percent of Participants Overall Survival at 24, 36, 48, 60, 72, and 84 Months Follow-Up - All Randomized Participants	Overall survival (OS) was defined as the time from randomization until death. Survival data were collected for up to 5 years on participants who had discontinued dasatinib treatment. Participants who did not die or who were lost to follow-up were censored on the last date the participant was known to be alive.	Baseline up to 84 Months Follow-up	No
Secondary	Baseline and After 2 Years Follow-Up: Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) That Led to Treatment Discontinuation	AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Baseline=closest to, but no later than, the first day of study drug for treated participants.	Baseline and after 2 Years Follow-Up	Yes
Secondary	Baseline and After 7 Years Follow-Up and Study Closure: Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) That Led toTreatment Discontinuation	AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Baseline=closest to, but no later than, the first day of study drug for treated participants. After the 2-year analysis and Protocol Amendment 02, those on a BID dosing schedule were allowed to switch to a QD dosing schedule. Due to the large number of participants switching from BID dosing to QD dosing, the abbreviated dosing data collection method incorporated in Amendment 03, the overall safety data are presented for the 100 mg QD group and combined for the other treatment groups.	Baseline to 30 days post last dose;7 years follow up; study closure July 2014	Yes

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