Study Evaluating SKI-606 (Bosutinib) In Philadelphia Chromosome Positive Leukemias

Chronic Myeloid Leukemia Clinical Trial

Official title:

A Phase 1/2 Study Of Bosutinib (SKI-606) In Philadelphia Chromosome Positive Leukemias

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00261846
• Other study ID #: 3160A4-200
• Secondary ID: B1871006, 3160A4
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: December 2, 2005
• Last updated: October 27, 2015
• Start date: March 2006
• Est. completion date: July 2015

Study information

• Verified date: October 2015
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This is an open-label, continuous daily dosing, two-part safety and efficacy study of SKI-606 (bosutinib) in Philadelphia chromosome positive leukemias (Ph+). Part 1 is a dose-escalation study in chronic phase Chronic Myelogenous Leukemia (CML) subjects to establish the maximum tolerated dose (MTD) in this subject population. Part 2 has begun after the completion of Part 1 and after a dose has been established for the compound in chronic phase subjects. Part 2 is a study of the the efficacy of 500mg daily oral SKI-606 (bosutinib) in patients with all phases of Ph+ CML and Ph+ Acute Lymphocytic Leukemia (ALL). The protocol will test the hypotheses that oral daily dosing of bosutinib at 500 mg will attain (1) Major Cytogenetic Response (MCyR) in chronic phase CML patients and (2) Overall Hematological Response (OHR) in advanced leukemia patients. Each phase of the disease will be evaluated as a separate cohort.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 571
• Est. completion date: July 2015
• Est. primary completion date: September 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Ph+ CML or Ph+ ALL who are primarily refractory to full-dose imatinib (600 mg), have disease progression/relapse while on full-dose imatinib, or are intolerant of any dose of imatinib.

• At least 3 months post stem cell transplantation

• Able to take daily oral capsules/tablets reliably

Exclusion Criteria:

• Subjects with Philadelphia chromosome, and bcr-abl negative CML

• Overt leptomeningeal leukemia

• Subjects without evidence of leukemia in bone marrow (extramedullary disease only)

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Abnormal Karyotype
• Chronic Myeloid Leukemia
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Philadelphia Chromosome

Intervention

Drug:
• Bosutinib
Part 1, starting dose 400 mg oral, daily dosing in the dose-escalation component. Part 2, 500 mg oral, continuous, daily dosing.

Locations

Country	Name	City	State
Argentina	Academia Nacional De Medicina	Buenos Aires
Argentina	Academia Nacional de Medicina-Instituto de Investigaciones Hematologicas	Buenos Aires
Argentina	Centro Medico Carlos M. Taquini	Buenos Aires
Argentina	Hospital Britanico	Buenos Aires
Argentina	Hospital Britanico	Buenos Aires
Argentina	Hospital Britanico de Buenos Aires	Buenos Aires
Argentina	Instituto de Investigaciones Hematologicas	Buenos Aires
Argentina	Instituto de Investigaciones Hematologicas	Buenos Aires
Argentina	Instituto Medico Especializado Alexander Fleming	Buenos Aires
Argentina	Academia Nacional de Medicina	Ciudad Autonoma de Buenos Airea
Argentina	Clinica del Sol	Ciudad Autonoma de Buenos Aires
Argentina	Centro Medico S.A.	Corrientes
Argentina	Hospital Jose Ramon Vidal	Corrientes
Argentina	Hospital Universitario Austral	Derqui-Pilar	Buenos Aires
Argentina	Hospital Italiano de la Plata	La Plata	Provincia de Buenos Aires
Argentina	Avda. J.D. Peron 1500	Pcia de Buenos Aires
Argentina	Hospital universitario austral	Pcia de Buenos Aires
Australia	Institute of Medical and Veterinary Science	Adelaide
Australia	Royal Adelaide Hospital - Pharmacist	Adelaide	South Australia
Australia	Royal Adelaide Hospital-Hematology Clinical Trials	Adelaide	South Australia
Australia	Royal Brisbane and Women's Hospital	Brisbane	Queensland
Australia	Royal Brisbane & Women's Hospital	Herston	Queensland
Australia	Royal Brisbane And Women's Hospital	Herston	Queensland
Australia	Royal Brisbane Hospital	Herston	Queensland
Australia	Clinical Haematology Alfred Hospital	Melbourn	Victoria
Australia	Clinical Haematology Alfred Hospital	Melbourne	Victoria
Australia	Icon Cancer Care	Milton
Australia	ICON Cancer Care (Haematology And Oncology Clinics Of Australasia (Hoca))-Milton	Milton	Queensland
Australia	Haematology and Oncology Clinics of Australia	Queensland
Australia	Royal Brisbane and Women's Hospital	Queensland
Australia	Haematology and Oncology Clinics of Australia	South Brisbane
Australia	Hematology and Oncology Clinics of Australia (HOCA), Mater Private Hospital	South Brisbane	Queensland
Australia	Mater Adult Hospital HAEMATOLOGY & ONCOLOGY CLINICS of AUSTRALIA	South Brisbane	Queensland
Australia	Mater Private Centre For Haematology & Oncology	South Brisbane	Queensland
Australia	Icon Cancer Care	Southport	Queensland
Austria	IV. Interne Abteilung	Grieskirchner
Austria	Klinikum Kreuzschwestern Wels	Wels
Brazil	Hospital de Clinicas - Universidade Federal do Parana	Alto da Gloria - Curitiba
Brazil	Hospital das Clinicas da Faculdade de Medicina da FMUSP	Cerqueira Cesar	SP
Brazil	Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo	Cerqueira Cesar	SP
Brazil	Hospital das Clinicas da FMUSP	Cerqueira Cesar	Sao Paulo
Brazil	Hospital das Clinicas da UFPR	Curitiba
Brazil	Hospital de Clinicas (HC)-Universidade Federal do Parana (UFPR)	Curitiba	Parana
Brazil	Hospital de Clinicas da Universidade Federal do Parana (HCUFPR)	Curitiba	PR
Brazil	Hospital das Clinicas da UFPR	Curitiba PR
Brazil	Hospital de Clinicas - Universidade Federal do Parana	Curitiba, PR
Brazil	Hospital Brigadeiro	Jardim Paulista	Sao Paulo
Brazil	Hospital Brigadeiro da Secretaria de Estado da Saude de Sao Paulo	Jardim Paulista	Sao Paulo
Brazil	Hospital Brigadeiro da Secretaria de Estado da Saude de Sao Paulo	Jardim Paulista	Sao Paulo/SP - Brazil
Brazil	Hospital Das Clinicas Da Faculdade De Medicina Da	Predio Dos Ambulatorios	Sao Paulo
Brazil	Centro de Estudos da Disciplina de Hematologia da Faculdade de Medicina do ABC	Santo Andre	Sao Paulo
Brazil	Centro de Estudos da Disciplina de Hematologia da Faculdade de Medicina do ABC	Santo Andre	SP - Bracil
Brazil	Centro de Estudos da Disciplina de Hematologia da Faculdade de Medicina do ABC	Santo Andre	SP
Brazil	Centro de Estudos e Pesquisas de Hematologia e Oncologia - Faculdade de Medicina do ABC	Santo Andre
Brazil	Centro de Estudos e Pesquisas de Hematologia e Oncologia da Faculdade de Medicina do ABC	Santo Andre	Sao Paulo
Brazil	Centro de Estudos e Pesquisas em Hematologia e Oncologia	Santo Andre
Brazil	Centro de Estudos e Pesqulsas de Heamatologia e oncologia	Santo Andre
Brazil	Faculdade De Medicina Do Abc	Santo Andre	SP
Brazil	Faculdade de Medicina do ABC	Santo Andre	SP
Brazil	Faculdade de Medicina do ABC - Centro de Estudos e Pesquisas de Hematologia e Oncologia	Santo Andre	Sao Paulo
Brazil	Fundacao do ABC - FMABC / Faculdade de Medicina ABC	Santo Andre	Sao Paulo
Brazil	CEPHO - Centro de Estudos e Pesquisa de Hematologia e Oncologia da Faculdade de Medicina	Santo Andro	SP
Brazil	Faculdade de Medicina da FMUSP - Fundacao Pro Sangue	Sao Paulo	SP
Brazil	Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo	Sao Paulo	SP
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Cross Cancer Institute, Department of Medical Oncology	Edmonton	Alberta
Canada	BC Cancer Agency - Cancer Centre for the Southern Interior	Kelowna	British Columbia
Canada	Jewish General Hospital	Montreal	Quebec
Canada	Sir Mortimer B. Davis, Jewish General Hospital	Montreal	Quebec
Canada	Princess Margaret Cancer Centre,University Health Network	Toronto	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	University Health Network - Princess Margaret Hospital - H-South Clinic	Toronto	Ontario
Canada	University Health Network Princess Margaret Hospital	Toronto	Ontario
Canada	CancerCare Manitoba - MacCharles Unit	Winnipeg	Manitoba
Chile	Instituto Clinico Oncologico del Sur	Temuco
China	Chinese People's Liberation Army General Hospital	Beijing
China	Department of Hematology	Beijing
China	Peking Union Medical college Hospital	Beijing
China	Peking Union Medical College Hospital of Chinese Academy of Medical Sciences	Beijing
China	The Chinese PLA General Hospital	Beijing	Beijing
China	The Department of Hematology	Beijing
China	The first affiliated Hospital of College of Medicine, Zhejiang University	Hangzhou
China	The first affiliated Hospital of Zhejiang University	Hangzhou	Zhejiang
China	Ruijing Hospital, Dept. of Medicine	Shanghai
China	The Hematology Hospital of Chinese Academy of Medical Sciences	Tianjin
China	The First Affiliated Hospital, School of Medicine	Zhejiang Province
Colombia	Fundacion Santa Fe de Bogota	Bogota	Cundinamarca
Colombia	Hospital Pablo Tobon Uribe	Medellin	Antioquia
Finland	Biomedicum Helsinki	Helsinki
Finland	Biomedicum Helsinki - Hematology Research Unit	Helsinki
Finland	Biomedicum Helsinki -Helsinki University Central Hospital	Helsinki
Finland	Helsinki University Central Hospital (HUCH)	Helsinki
Finland	Helsinki University Central Hospital (HUCH)	Helsinki
Finland	Helsinki University Hospital	Helsinki
Germany	Universitaetsklinikum Carl Gustav Carus	Dresden
Germany	Universitatsklinikum Carl Gustav Carus an der Technischen Universität Dresden	Dresden
Germany	Universitätsklinikum Carl Gustav Carus, der Technischen Universitat Dresden	Dresden
Germany	University Hospital Carl Gustav Carus	Dresden
Germany	Universitaetsklinikum Hamburg - Eppendorf	Hamburg
Germany	Universitaetsklinikum Hamburg-Eppendorf	Hamburg
Germany	Universitaetsklinikum Magdeburg A. oe. R.	Magdeburg
Germany	III Medizinische Klinik und Poliklinik	Mainz
Germany	Klinikum der Johann Gutenberg Universitaet Mainz	Mainz
Germany	Universitaet Mainz	Mainz	RP
Germany	Universitaet Mainz Iii. Medizinische Klinik Abteilung Fuer Haematologie	Mainz
Germany	Universitaetsklinikum Mainz	Mainz
Germany	III. Medizinische Klinik	Mannheim
Germany	Universitaetsmedizin Mannheim, CML-Studienzentrale	Mannheim
Hong Kong	Pamela Youde Nethersole Eastern Hosp.	Chai Wan
Hong Kong	Pamela Youde Nethersole Eastern Hospital	Chai Wan
Hong Kong	Queen Mary Hospital	Hong Kong
Hungary	Egyesitett Szent Istvan es Szent Laszlo Korhaz / Haematologia es Ossejt-Transzplantacios osztaly	Budapest
Hungary	Egyesitett Szent Istvan es Szent Laszlo Korhaz-Rendelointezet	Budapest
Hungary	Fovarosi Onkormanyzat Egyesitett Szent Istvan es Szent Laszlo	Budapest
Hungary	Fovarosi Onkormanyzat Szent Laszlo Korhaz	Budapest
Hungary	St. Istvan and St. Laszlo Hospital of Budapest	Budapest
India	Christian Medical College	Vellore	Tamil Nadu
Italy	Policlinico S. Orsola-Malpighi	Bologna
Italy	Policlinico Sant' Orsola-Malpighi	Bologna
Italy	University of Bologna	Bologna	Province of Bologna
Italy	Azienda Ospedaliera San Gerardo	Monza
Italy	AOU San Luigi Gonzaga	Orbassano
Italy	Azienda Ospedaliero - Universitaria San Luigi Gonzaga	Orbassano	Torino
Korea, Republic of	Dept. of Hematology	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary Hospital	Seoul
Mexico	Hospital Universitario "Dr. Jose Eleuterio Gonzalez"	Monterrey	Nuevo Leon
Mexico	Hospital Universitario De Nuevo Leon	Monterrey	Nuevo Leon
Mexico	UANL	Neuvo Leon
Mexico	Hospital Universitario "Dr. Jose Eleuterio Gonzalez"	Nuevo Leon
Mexico	Centro Oncologico Estatal Issemym	Toluca
Mexico	Centro Oncologico Estatal ISSEMYM	Toluca	Estado de Mexico
Mexico	Centro Oncologico Estatal Issemym	Toluca, Estado De Mexico
Netherlands	VU University Medical Center	Amsterdam
Netherlands	LEC	Groningem
Netherlands	UMCG - Pharmacy	Groningen
Netherlands	Universitair Medisch Centrum Groningen	Groningen
Netherlands	University Medical Center Groningen	Groningen
Netherlands	VUMC	The Netherlands
Norway	Avd. for blodsykdommer	Trondheim	Norge
Norway	St. Olav's Hospital	Trondheim
Peru	Hospital Nacional Edgardo Rebagliati Martins	Jesus Maria	Lima - Peru
Peru	Edgardo Rebegliati Martins National Hospital	Lima
Peru	Hospital Nacional Edgardo Rebagliati Martins	Lima
Russian Federation	State Healthcare Institution, Sverdlovsk Regional Clinical Hospital	Ekaterinburg
Russian Federation	Hematology Clinic	Kirov
Russian Federation	Kirov Research Institute of Hematology and Blodd transfusion of Roszdrav - Hematology Clinic	Kirov
Russian Federation	Kirov Research Institute Of Hematology And Blood Transfusion Of Rosmedtechnology	Kirov
Russian Federation	Federal State Budget Institution Hematology Scientific Center of Minzdravsotsrazvitiya of Russia	Moscow
Russian Federation	Hematological Research Centre of RAMS	Moscow
Russian Federation	Moscow regional Clinical Research Institute named after M.F Vladimirsky	Moscow
Russian Federation	Rostov State Medical University of Roszdrav	Rostov-on Don
Russian Federation	City Hospital N 31	Saint-Petersburg	St. Peterburg
Russian Federation	Academician IPPavlov St. Petersburg state medical university	St. Petersburg
Russian Federation	St-Petersburg Pavlov's State Medical University	St. Petersburg
Singapore	Singapore General Hospital, Department of Haematology	Singapore
South Africa	Department of Haematology and Cell Biology	Bloemfontein
South Africa	University of Free State	Bloemfontein
South Africa	University of the Free State	Bloemfontein
South Africa	Division of Haematology	Cape Town
South Africa	University of Cape Town	Cape Town
South Africa	Wits Clinical Research	Johannesburg
South Africa	Wits Donald Gordon Clinical Trial Site	Johannesburg	Gauteng
South Africa	Johannesburg Hospital	Parktown
South Africa	University of the Witwatersrand Oncology	Parktown
South Africa	University of Witwatersrand Oncology, Donald Gordon Medical Centre	Parktown	Johannesburg
South Africa	University Witwatersrand Oncology	Parktown
South Africa	University Witwatersrand Oncology-Johannesburg Hospital	Parktown
South Africa	Wits Donald Gordon Clinical Trial Site	Parktown	Johannesburg
South Africa	Wits Donald Gordon Clinical Trial Site	Parktown
South Africa	Chris Hani Baragwanath Hospital	Soweto
South Africa	Clinical Haematology Unit	Soweto
South Africa	WCR: Wits Clinical Research	Soweto
South Africa	Wits Clinical Research	Soweto
South Africa	Wits Clinical Research, Chris Hani Baragwanath Hospital	Soweto	Gauteng
Spain	Hospital Clinic de Barcelona (Hospital Clinic i Provincial)	Barcelona	Catalonia
Spain	Hospital Universitari Clinic de Barcelona	Barcelona	Catalonia
Spain	Hospital Universitario La Princesa	Madrid
Spain	Hospital Clinico Universitario de Valencia (CHUV)	Valencia
Sweden	Akademiska Sjukhuset Uppsala	Uppsala
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	National Taiwan University Hospital - Section of Hematology-Oncology	Taipei 100
United Kingdom	Department of Haematology	London
United Kingdom	Department of Haematology, Hammersmith Hospital	London
United Kingdom	Hammersmith Hospital	London
United Kingdom	Hammersmith Hospital	London	Greater London
United Kingdom	Imperial College London Hammersmith Hospital-Catherine Lewis Centre	London
United Kingdom	Newcastle University - School of Clinical and Laboratory Sciences	Newcastle
United Kingdom	Department of Haematology	Newcastle Upon Tyne	North East England
United Kingdom	Freeman Hospital, Nothern Centre for Cancer Care	Newcastle upon Tyne
United Kingdom	Northern Centre for Cancer Care - The Newcastle Upon Tyne Hospitals - NHS Foundation Trust	Newcastle Upon Tyne	North East England
United Kingdom	Nothern Centre for Cancer Care Freeman Hospital	Newcastle upon Tyne
United Kingdom	Royal Victoria Infirmary - Clinical Research Facility	Newcastle Upon Tyne
United Kingdom	Royal Victoria Infirmary-The Newcastle Upon Tyne Hospitals NHS Foundation Trust	Newcastle upon Tyne
United Kingdom	Department of Haematology, University of Newcastle	North East England
United Kingdom	Freeman Hospital Northern Centre for Cancer Care	North East England
United Kingdom	Newcastle University School of Clinical and Laboratory Sciences	North East England
United Kingdom	University of Newcastle - Royal Victoria Infirmary	North East England
United Kingdom	School of Clinical and Laboratory Sciences	University upon Tyne	North East England
United States	Emory Clinic	Atlanta	Georgia
United States	Emory University Hospital	Atlanta	Georgia
United States	Investigational Drug Service (Drug Ship)	Atlanta	Georgia
United States	Winship Cancer Institute	Atlanta	Georgia
United States	University Of Maryland	Baltimore	Maryland
United States	University Of Maryland Medical Center	Baltimore	Maryland
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Rocky Mountain Cancer Center	Denver	Colorado
United States	City of Hope	Duarte	California
United States	City of Hope National Medical Center	Duarte	California
United States	Hudson Valley Hematology and Oncology Associates	Hawthorne	New York
United States	Westchester Oncology Hematology Group, P.C.	Hawthorne	New York
United States	Penn State, Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	MD Anderson Cancer Center	Houston	Texas
United States	The University of Texas	Houston	Texas
United States	Franciscan St Francis Health, Inc.	Indianapolis	Indiana
United States	Indiana Blood and Marrow Transplantation Research	Indianapolis	Indiana
United States	Indiana Blood and Marrow Transplantation Research-Franciscan St Francis Health Center Inc.	Indianapolis	Indiana
United States	New York Presbyterian Hospital	New York	New York
United States	New York Presbyterian Hospital	New York	New York
United States	New York Presbyterian Hospital at Cornell	New York	New York
United States	Weill Cornell Medical Center	New York	New York
United States	Weill Cornell Medical Center	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Oncology Specialists, SC	Niles	Illinois
United States	Oncology Specialists S.C.	Park Ridge	Illinois
United States	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia
United States	University of Rochester Cancer Center Pharmacy	Rochester	New York
United States	University of Rochester Medical Center Strong Memorial Hospital - James P. Wilmot Cancer Center	Rochester	New York
United States	Louisiana State University Health Sciences Center, Feist-Weiller Cancer Center	Shreveport	Louisiana
United States	LSU Health Sciences Center	Shreveport	Louisiana
United States	Westchester Medical Center	Valhalla	New York
United States	Georgetown University Hospital	Washington	District of Columbia
United States	Georgetown University Medical Center	Washington	District of Columbia
United States	Georgetown University Medical Center	Washington	District of Columbia
United States	Lombardi Cancer Center	Washington	District of Columbia
United States	The George Washington University Medical Faculty Associates (Gwmfa)	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Brazil,  Canada,  Chile,  China,  Colombia,  Finland,  Germany,  Hong Kong,  Hungary,  India,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Norway,  Peru,  Russian Federation,  Singapore,  South Africa,  Spain,  Sweden,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Dose Limiting Toxicity (DLT)	DLT was defined as any of the following events occurring during the first 28 days of study medication and considered at least possibly-related to study medication: any grade 3 or 4 clinically-relevant non-hematologic toxicity, any clinically-significant grade 2 non-hematologic toxicity that requires 14 days to resolve (to grade 1).	Part 1 Baseline up to Day 28	Yes
Primary	Maximum Tolerated Dose (MTD)	MTD was defined as highest dose level for which no more than 1 participant in a dose cohort experienced DLT. DLT was defined as any of the following events occurring during the first 28 days of study medication and considered at least possibly-related to study medication: any grade 3 or 4 clinically-relevant non-hematologic toxicity, any clinically-significant grade 2 non-hematologic toxicity that requires 14 days to resolve (to grade 1).	Part 1 Baseline up to Day 28	Yes
Primary	Maximum Observed Plasma Concentration (Cmax) - Part 1		0 (pre-dose), 1, 2, 3, 4, 6, 8, 24, 48 hours post-dose on Day 1	No
Primary	Time to Reach Maximum Observed Plasma Concentration (Tmax) - Part 1		0 (pre-dose), 1, 2, 3, 4, 6, 8, 24, 48 hours post-dose on Day 1	No
Primary	Plasma Decay Half-Life (t1/2) - Part 1	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	0 (pre-dose), 1, 2, 3, 4, 6, 8, 24, 48 hours post-dose on Day 1	No
Primary	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) - Part 1	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).	0 (pre-dose), 1, 2, 3, 4, 6, 8, 24, 48 hours post-dose on Day 1	No
Primary	Area Under the Concentration-Time Curve (AUC) - Part 1	AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. There were fewer participants evaluable for AUC values than participants evaluable for AUClast because terminal half-life of some participants was not accurately estimated and therefore AUC in these participants was not calculated.	0 (pre-dose), 1, 2, 3, 4, 6, 8, 24, 48 hours post-dose on Day 1	No
Primary	Apparent Oral Clearance (CL/F) - Part 1	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.	0 (pre-dose), 1, 2, 3, 4, 6, 8, 24, 48 hours post-dose on Day 1	No
Primary	Apparent Volume of Distribution (Vz/F) - Part 1	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.	0 (pre-dose), 1, 2, 3, 4, 6, 8, 24, 48 hours post-dose on Day 1	No
Primary	Maximum Observed Plasma Concentration at Steady State (Cmax,ss) - Part 1	Maximum plasma concentration over 24 hours at steady state (ss), on Day 15.	0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 15	No
Primary	Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss) - Part 1	Time to reach maximum observed plasma concentration over 24 hours at steady state (ss), on Day 15.	0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 15	No
Primary	Plasma Decay Half-Life at Steady State (t1/2,ss) - Part 1	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Plasma decay half-life over 24 hours at steady state (ss), on Day 15 was calculated.	0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 15	No
Primary	Area Under the Concentration-Time Curve at Steady State (AUCss) - Part 1	AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. AUC over 24 hours at steady state (ss), on Day 15 was calculated.	0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 15	No
Primary	Apparent Oral Clearance at Steady State (CL/F,ss) - Part 1	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. Apparent oral clearance over 24 hours at steady state (ss), on Day 15 was calculated.	0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 15	No
Primary	Accumulation Ratio (R)	R=accumulation ratio (AUCss on Day 15/AUC[0-24] on Day 1)	0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 hours post-dose on Day 1 and Day 15	No
Primary	Percentage of Participants With Major Cytogenetic Response (MCyR) at Week 24 in Chronic Phase Second-line Imatinib Resistant CML Population - Part 2	Cytogenetic response (CyR) is based on the prevalence of Philadelphia positive (Ph+) cells. Major cytogenetic response was categorized as either complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR). CCyR was achieved when there was 0 percent (%) Ph+ cells and PCyR was achieved when 1 to 35% Ph+ cells.	Week 24	No
Primary	Population Pharmacokinetics - Part 2	Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.	0 (pre-dose), 2, 4, 6 hours on Day 1, Day 21, 20-23 hours post-dose on Day 21, 0 (pre-dose) hours on Day 84, 168, 252	No
Secondary	Percentage of Participants With Major Cytogenetic Response (MCyR) - Part 1	Cytogenetic response (CyR) is based on the prevalence of Philadelphia positive (Ph+) cells. Major cytogenetic response was categorized as either complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR). CCyR was achieved when there was 0 percent (%) Ph+ cells and PCyR was achieved when 1 to 35% Ph+ cells.	Baseline, thereafter assessed every 12 weeks up to 2 years then every 24 weeks up to Year 5	No
Secondary	Phosphorylation Inhibition of Breakpoint Cluster Region-Abelson Kinase (Bcr-Abl) - Part 1	bcr-Abl is a protein resulting from the transcription of the Philadelphia chromosome following 9:22 chromosomal translocation, and phosphorylation inhibition of which correlates with inhibition of tumor cell growth.	Baseline, Week 4, 8, 12, thereafter assessed every 12 weeks up to 2 years then every 24 weeks up to Year 5	No
Secondary	Phosphorylated Cancer-Testis 10 (CT10) Regulator of Kinase Like (p-CrkL) Protein Level in Blood at Baseline - Part 1	CrkL is a protein, phosphorylation of which has been shown to correlate with CML cell growth; and conversely inhibition of their phosphorylation correlates with inhibition of tumor cell growth. Phosphorylation of CrkL was monitored in whole blood cells by using fluorescent activated cell sorter (FACS) flow cytometry. Amount of CrkL protein phosphorylated (in moles) per 100 blood cells was reported.	0 (pre-dose) on Day 1 (Baseline)	No
Secondary	Percent Change From Baseline in Phosphorylated Cancer-testis 10 (CT10) Regulator of Kinase Like (p-CrkL) Protein Level in Blood at Day 1, 8 and 15 - Part 1	CrkL is a protein, phosphorylation of which has been shown to correlate with CML cell growth; and conversely inhibition of their phosphorylation correlates with inhibition of tumor cell growth. Phosphorylation of CrkL was monitored in whole blood cells by using FACS flow cytometry. Percent change in p-CrkL protein at different time points give measure of phosphorylation inhibition from baseline.	6 hours post-dose on Day 1, 0 (pre-dose), 6 hours post-dose on Day 8, 15	No
Secondary	Percentage of Participants With Major Cytogenetic Response (MCyR) in Chronic Phase Second-line Imatinib Intolerant CML and Chronic Phase Third-line CML Population - Part 2	Cytogenetic response (CyR) is based on the prevalence of Philadelphia positive (Ph+) cells in metaphase from Bone Marrow (BM) sample. Major cytogenetic response was categorized as either complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR). CCyR was achieved when there was 0 percent (%) Ph+ cells in metaphase in BM and PCyR was achieved when 1 to 35% Ph+ cells in metaphase in BM.	Week 24 for second line, Baseline through Week 24 for third line	No
Secondary	Percentage of Participants With Major Cytogenetic Response (MCyR) in Chronic Phase Second-line CML and Chronic Phase Third-line CML - Part 2	Cytogenetic response (CyR) is based on the prevalence of Philadelphia positive (Ph+) cells in metaphase from Bone Marrow (BM) sample. Major cytogenetic response was categorized as either complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR). CCyR was achieved when there was 0% Ph+ cells in metaphase in BM and PCyR was achieved when 1 to 35% Ph+ cells in metaphase in BM.	Baseline, Week 12, thereafter assessed every 12 weeks up to 2 years then every 24 weeks up to Year 5	No
Secondary	Duration of Major Cytogenetic Response (MCyR) in Chronic Phase Second-line CML and Chronic Phase Third-line CML - Part 2	Duration of MCyR was defined as the interval from the date of the earliest demonstration of a response, until the earliest date of loss of that response.; Duration of response in weeks = (date of confirmed loss of first attained response minus date of first attained response)/7 days. Major cytogenetic response was categorized as either complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR). CCyR was achieved when there was 0 percent (%) Ph+ cells in metaphase in BM and PCyR was achieved when 1 to 35% Ph+ cells in metaphase in BM.	Baseline, Week 12, thereafter assessed every 12 weeks up to 2 years then every 24 weeks up to Year 5	No
Secondary	Time to Achieve Major Cytogenetic Response (MCyR) in Chronic Phase Second-line CML and Chronic Phase Third-line CML - Part 2	Time to MCyR was the interval from the date of first dose of study medication until the first date of achieving a given response.; Time to response in weeks = (event date - first dose date plus 1)/7, where the event date is the non-missing date of the first attained response or last cytogenetic assessment date of a participants. Major cytogenetic response was categorized as either complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR). CCyR was achieved when there was 0 percent (%) Ph+ cells in metaphase in BM and PCyR was achieved when 1 to 35% Ph+ cells in metaphase in BM.	Baseline, Week 12, thereafter assessed every 12 weeks up to 2 years then every 24 weeks up to Year 5	No
Secondary	Duration of Complete Hematologic Response (CHR) - Part 2	The duration of CHR was defined as the interval from the first date of response until the first date of confirmed loss of response. Duration of response in weeks =(date of confirmed loss of first attained response - date of first attained response)/7. CHR response was considered to be achieved if participants met all of the following criteria: White Blood Cells =< institutional upper limit of normal, no peripheral blood blasts or promyelocytes, myelocytes+metamyelocytes <5% in blood, absolute neutrophil count >=1.0*10^9 per liter (/L), platelets >=100 but <450*10^9/L unless related to therapy, <20% basophils in blood and no extramedulary involvement (including hepato- or splenomegaly), =<5% BM blasts.	Baseline, Day 1 and 7 of Week 1, Day 7 of Week 2, 3, 4, 8, 12, thereafter assessed every 12 weeks up to 2 years then every 24 weeks up to Year 5	No
Secondary	Time to Achieve Complete Hematologic Response (CHR) - Part 2	The time to CHR was measured from the date of first dosing to the first date of response. Time to response in weeks = (event date - first dose date plus 1)/7, where the event date is the non-missing date of the first attained response or last assessment date of a participant. Hematologic response was considered to be achieved if participants met all of the following criteria of CHR: White Blood Cells =< institutional upper limit of normal, no peripheral blood blasts or promyelocytes, myelocytes+metamyelocytes <5% in blood, absolute neutrophil count >= 1.0*10^9 per liter (/L), platelets >=100*10^9/L but <450*10^9/L, <20% basophils in blood and no extramedulary involvement (including hepato- or splenomegaly), =<5% BM blasts.	Baseline, Day 1 and 7 of Week 1, Day 7 of Week 2, 3, 4, 8, 12, thereafter assessed every 12 weeks up to 2 years then every 24 weeks up to Year 5	No
Secondary	Progression Free Survival (PFS) Rate - Part 2	PFS was based on Kaplan-Meier estimates. PFS was defined as time in weeks from start of study treatment to treatment discontinuation due to disease progression as assessed by the investigator. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from death case report forms (CRFs).	Baseline up to Year 1, Year 2	No
Secondary	Overall Survival (OS) Rate - Part 2	OS was based on Kaplan-Meier method. Survival was defined as the time period from the date of first dose of bosutinib to the date of death, censored at the participant's last contact date.	Baseline up to Year 2	No
Secondary	Percentage of Participants With Complete Hematologic Response (CHR) in Advanced Leukemia Population - Part 2	Hematologic response was considered to be achieved if participants met all of the following criteria of CHR: White Blood Cells =< institutional upper limit of normal, no peripheral blood blasts or promyelocytes, myelocytes+metamyelocytes <5% in blood, absolute neutrophil count >= 1.0*10^9 per liter (/L), platelets >=100*10^9/L but <450*10^9/L, <20% basophils in blood and no extramedulary involvement (including hepato- or splenomegaly), =<5% BM blasts.	Baseline, Day 1 and 7 of Week 1, Day 7 of Week 2, 3, 4, 8, 12, thereafter assessed every 12 weeks up to 2 years then every 24 weeks up to Year 5	No
Secondary	Percentage of Participants With Overall Hematologic Response (OHR) by Week 48 in Advanced Leukemia Population - Part 2	OHR included CHR, no evidence of leukemia (NEL), minor hematologic response (MiHR) or return to chronic phase (RCP), participants had to meet at least 1 of this criterion. Criteria for RCP: disappearance of features defining AP/BP, but still in CP and persistence of clonal evolution. Criteria for MiHR: <15% blasts in blood and BM, <30% blasts+promyelocytes in blood and BM, <20% basophils in blood, no extramedullary disease other than liver/spleen. Criteria for CHR and NEL: <20% basophils in blood, no extramedullary involvement including liver/spleen, no peripheral blasts or promyelocytes, myelocytes + metamyelocytes <5% in blood, <5% (NEL) and <=5% (CHR) marrow blasts, 0.5*10^9 <= Absolute neutrophil count (ANC) <1.0*10^9/L (NEL) and ANC>=1.0*10^9/L (CHR), 20*10^9 <=platelets<100 *10^9/L (NEL) and platelets>=100 but <450x10^9/L (CHR), white blood cells <=institutional upper limit of the normal range.	Week 48	No
Secondary	Percentage of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state.	Baseline up to follow up visit (30 days after last dose of study treatment)	No
Secondary	Duration of Potentially Clinically Important (PCI) Adverse Events (AEs)	An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. PCI-AEs included hepatotoxicity, gastrointestinal toxicity: diarrhea, nausea, vomiting, hypersensitivity reactions, rash, edema, effusion, myelosuppression, hemorrhage, infection, cardiac events. Duration of AE was calculated as (stop date minus start date) plus 1 for non-missing and non-partial dates.	Baseline up to follow up visit (30 days after last dose of study treatment)	Yes
Secondary	Number of Participants With Change From Baseline in Laboratory Tests Results	Laboratory values included urinalysis, complete blood count (CBC), prothrombin time/partial thromboplastin time (PT/PTT), international normalized ratio (INR), blood chemistry and serum pregnancy test (ß-HCG). Potentially clinically important (PCI) changes in laboratory assessments were reported. Any laboratory value that was identified as clinically significant was reported as an AE. PCI laboratory values were defined as National Cancer Institute Common Toxicity Criteria for Adverse Events Version 3.0 (NCI CTCAE v3.0) grade 3 or higher.	Week 1, 2, 3, 4, 8, 12, thereafter assessed every 12 weeks up to 2 years then every 24 weeks up to Year 5	Yes
Secondary	Number of Participants With Change From Baseline in Electrocardiogram (ECG) Findings	Criteria for PCI changes in ECG (12-lead) were defined as: no sinus rhythm; PR interval >=220 msec and increase of >=20 msec; QRS interval >=120 msec; QT interval corrected using the Fridericia formula (QTcF) and QT interval corrected using the Bazett's formula (QTcB) >500 msec or increase of >60 msec; heart rate <=45 beats per minute (bpm) or >=120 bpm or decrease/increase of >=15 bpm.	Baseline, 0 (pre-dose), 2, 4, 6 hours on Day 1, 0 (pre-dose), 2, 4, 6, 20-23 hours on Day 21, and end of treatment visit	Yes
Secondary	Number of Participants With Change From Baseline in Findings of Chest X-ray		Baseline, Week 8, and end of treatment	Yes
Secondary	Number of Participants Who Received Concomitant Medications for Management of Adverse Events (AEs)	Number of participants taking any non-study medications which were administered from Study Day 1 to 30 days after last dose of study treatment as a management of an AE are reported.	Baseline up to end of treatment (Year 5)	Yes
Secondary	Number of Participants With Change From Baseline in Eastern Co-operative Oncology Group Performance Status (ECOG-PS)	ECOG-PS measured on-therapy (time between first dose and last dose date with a 30-day lag) assessed participant's performance status on 5 point scale: 0=Fully active/able to carry on all pre-disease activities without restriction; 1=restricted in physically strenuous activity, ambulatory/able to carry out light or sedentary work; 2=ambulatory (>50% of waking hrs), capable of all self care, unable to carry out any work activities; 3=capable of only limited self care, confined to bed/chair >50% of waking hrs; 4=completely disabled, cannot carry on any self care, totally confined to bed/chair; 5=dead.	Baseline, Week 1, 2, 8, 12, thereafter assessed every 12 weeks up to 2 years then every 24 weeks up to Year 5	Yes
Secondary	Number of Participants With Change From Baseline in Physical Examinations and Vital Signs	Number of participants with PCI physical examinations and vital signs is reported during therapy and at post therapy. Criteria for PCI change in vital signs: heart rate value of <40 beats per minute and value >150 beats per minute, systolic blood pressure (SBP) of <80 or >210 millimeter of mercury (mmHg), diastolic blood pressure (DBP) of <40 or >130 mmHg, temperature <32 or >40 degree centigrade, respiratory rate of <10 or >50 breaths/minute and criteria for PCI change in physical examination: >=10% increase or decrease of body weight (Wt) in kilogram (kg).	Baseline up to end of treatment (Year 5)	Yes

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