Bosutinib Treatment Extension Study Only For Subjects With Chronic Myeloid Leukemia (CML) Who Have Previously Participated In Bosutinib Studies B1871006 Or B1871008

AN OPEN-LABEL BOSUTINIB TREATMENT EXTENSION STUDY FOR SUBJECTS WITH CHRONIC MYELOID LEUKEMIA (CML) WHO HAVE PREVIOUSLY PARTICIPATED IN BOSUTINIB STUDIES B1871006 OR B1871008

The objective of the study is to provide long term access to bosutinib treatment and assess long term safety, tolerability and duration of clinical benefit, without any formal hypothesis testing; therefore, there is no formal primary endpoint.

Study Overview

• Status: Completed
• Conditions: Chronic Myeloid Leukemia
• Intervention / Treatment: Drug: bosutinib

• Study Type: Interventional
• Enrollment (Actual): 281
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Argentina
  • Corrientes, Argentina, 3400
    • Hospital Dr. Jose Ramon Vidal
  • Buenos Aires
    • Cd. Autonoma De Buenos Aires, Buenos Aires, Argentina, C1426ANZ
      • Instituto Medico Especializado Alexander Fleming
    • La Plata, Buenos Aires, Argentina, 1900
      • Hospital Italiano de La Plata
• Australia
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane & Women's Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
• Belgium
  • Charleroi, Belgium, 6000
    • GHDC (Grand Hopital de Charleroi)
• Brazil
  • SP
    • Campinas, SP, Brazil, 13083-878
      • Universidade Estadual de Campinas / Centro de Hematologia e Hemoterapia
    • Santo Andre, SP, Brazil, 09060-650
      • Faculdade de Medicina do ABC - Centro de Estudos e Pesquisa em Hematologia e Oncologia (CEPHO)
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Alberta Health Services - Department of Medical Oncology - Cross Cancer Institute
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z1M9
      • Vancouver General Hospital
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Sir Mortimer B. Davis-Jewish General Hospital
• Chile
  • V Region
    • Renaca, V Region, Chile, 2540364
      • Instituto Oncologico, Clinica Renaca
    • Renaca, V Region, Chile, 2540488
      • Instituto Oncologico
• China
  • Beijing, China, 100853
    • Chinese People's Liberation Army General Hospital
  • Shanghai, China, 200025
    • Ruijin Hospital- Shanghai Jiaotong University School of Medicine
  • Tianjin, China, 300020
    • Blood Disease Hospital, Chinese Academy of Medical Science & Peking Union Medical College
  • Beijing
    • Beijing, Beijing, China, 100730
      • Peking Union Medical College Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital of College of Medicine, Zhejiang University
• Colombia
  • Cundinamarca
    • Bogota, Cundinamarca, Colombia, 110111
      • Fundacion Santa Fe de Bogota
• Finland
  • Helsinki, Finland, 00290
    • Helsingin Yliopistollinen Keskussairaala, Hematologian poliklinikka
• France
  • Caen Cedex 9, France, 14033
    • CHU de Caen
  • Nantes cedex 1, France, 44093
    • CHU Hotel Dieu - Service Hematologie
  • Poitiers, France, 86021
    • CHU Poitiers
  • Poitiers Cedex, France, 86021
    • Chu de Poitiers
  • Strasbourg, France, 67000
    • Strasbourg Oncologie Liberale -Centre de Radiotherapie, Clinique Ste Anne
• Hong Kong
  • Chai Wan, Hong Kong
    • Pamela Youde Nethersole Eastern Hospital
  • Shatin, New Territories, Hong Kong
    • Department of Medicine & Therapeutics, Prince of Wales Hospital
• Hungary
  • Budapest, Hungary, 1097
    • Egyesitett Szent Istvan es Szent Laszlo Korhaz-Rendelointezet
  • Kaposvar, Hungary, 7400
    • Somogy Megyei Kaposi Mor Oktato Korhaz, Belgyogyaszati Osztaly
• India
  • Tamil NADU
    • Vellore, Tamil NADU, India, 632004
      • Christian Medical College. Vellore
• Italy
  • Roma, Italy, 00144
    • Ospedale S. Eugenio - UOC Ematologia
  • BO
    • Bologna, BO, Italy, 40138
      • A.O.U. Policlinico S.Orsola Malpighi
  • Monza AND Brianza
    • Monza, Monza AND Brianza, Italy, 20090
      • ASST Monza - Ospedale San Gerardo
  • TO
    • Orbassano, TO, Italy, 10043
      • A.O.U. San Luigi Gonzaga di Orbassano
• Japan
  • Tokyo, Japan, 113-8677
    • Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital
  • Aichi
    • Toyohashi, Aichi, Japan, 4418570
      • Toyohashi Municipal Hospital
  • Akita
    • Akita City, Akita, Japan, 010-8543
      • Akita University Hospital
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan, 811-1395
      • National Hospital Organization Kyushu Cancer Center
  • Ishikawa
    • Kanazawa-shi, Ishikawa, Japan, 920-8641
      • Kanazawa University Hospital
  • Osaka
    • Osakasayama-city, Osaka, Japan, 589-8511
      • Kindai University Hospital
    • Suita-city, Osaka, Japan, 565-0871
      • Osaka University Hospital
  • Shizuoka
    • Hamamatsu-shi, Shizuoka, Japan, 431-3192
      • Hamamatsu University School of Medicine University Hospital
• Korea, Republic of
  • Seoul, Korea, Republic of, 06591
    • The Catholic University of Korea, Seoul St. Mary's Hospital
• Latvia
  • Riga, Latvia, LV-1079
    • Riga East Clinical University Hospital
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • VU University Medical Center
  • Groningen, Netherlands, 9713 GZ
    • University Medical Center Groningen, Department of Hematology
• Peru
  • Lima, Peru, 11
    • Unidad de Investigacion de Hematologia - Hospital Nacional Edgardo Rebagliati Martins
• Poland
  • Gdansk, Poland, 80-214
    • Uniwersyteckie Centrum Kliniczne
  • Gdańsk, Poland, 80-952
    • Uniwersyteckie Centrum Kliniczne
  • Krakow, Poland, 31-501
    • SP ZOZ Szpital Uniwersytecki w Krakowie
  • Lublin, Poland, 20-081
    • Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
• Russian Federation
  • Moscow, Russian Federation, 125167
    • Federal State-Funded Institution National Research Center of Hematology of the Ministry of
  • Rostov-on-Don, Russian Federation, 344022
    • State Budgetary Educational Institution of Higher Professional Education
  • Rostov-on-Don, Russian Federation, 344015
    • State Budgetary Institution of Rostov Region - Rostov Regional Clinical Hospital
  • Saint Petersburg, Russian Federation, 194291
    • State Budgetary Institution of Healthcare - Leningrad Regional Clinical Hospital
  • Saint Petersburg, Russian Federation, 197022
    • Clinic "Institute of Pediatric Oncology, Hematology and Transplantation n.a. R.M. Gorbachova"
  • Saint Petersburg, Russian Federation, 197341
    • Federal State Budgetary Institution "Federal Almazov Medical Research Centre"
  • Samara, Russian Federation, 443095
    • State Budgetary Institution of Healthcare Samara Regional Clinical Hospital n.a. V.D. Seredavin
  • Sverdlovsk Region
    • Ekaterinburg, Sverdlovsk Region, Russian Federation, 620102
      • State Budgetary Institution of Healthcare of Sverdlovsk Region
• Singapore
  • Singapore, Singapore, 169608
    • Singapore General Hospital
• South Africa
  • Gauteng
    • Soweto, Gauteng, South Africa, 2013
      • Wits Clinical Research-Chris Hani Baragwanath Hospital
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic Barcelona
  • Madrid, Spain, 28006
    • Hospital Universitario La Princesa
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28050
    • Hospital Universitario Madrid Sanchinarro, Centro Integral Oncologico Clara Campal
  • Toledo, Spain, 45004
    • Hospital Virgen de la Salud
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia (CHUV)
• Thailand
  • Bangkok, Thailand, 10700
    • Division of Hematology, Department of Medicine, Faculty of Medicine, Siriraj Hospital,
• Turkey
  • Ankara, Turkey, 06100
    • Hacettepe Universitesi Tip Fakultesi
  • Sehit Kamil
    • Gaziantep, Sehit Kamil, Turkey, 27310
      • Gaziantep Universitesi Tip Fakultesi Sahinbey Uygulama ve Arastirma Hastanesi
• Ukraine
  • Cherkasy, Ukraine, 18009
    • Municipal Institution "Cherkasy Regional Oncology Dispensary"
  • Dnipropetrovsk, Ukraine, 49102
    • MI "Dnipropetrovsk City Multi-field Clinical Hospital #4" of DRC Hematology Center
  • Kyiv, Ukraine, 03115
    • State Institution "National Research Center for Radiation Medicine of the National Academy of
  • Kyiv, Ukraine, 04112
    • Kyiv City Clinical Hospital #9, SI "Institute of Hematology and Transfusiology of NAMS of Ukraine"
  • Lviv, Ukraine, 79044
    • State Institution "Institute of Blood Pathology and Transfusion Medicine of
• United Kingdom
  • Newcastle Upon Tyne, United Kingdom, NE7 7DN
    • Freeman Hospital
  • Nottinhgam, United Kingdom, NG5 1PB
    • Nottingham University Hospitals Nhs Trust
• United States
  • Florida
    • Orlando, Florida, United States, 32806
      • Orlando Health, Inc
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute, Emory University
    • Atlanta, Georgia, United States, 30322
      • The Emory Clinic
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital, Inc. - Central Research Department
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital Inc., - GCS/Northside
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Indiana Blood and Marrow Transplantation
  • Iowa
    • Sioux City, Iowa, United States, 51101
      • Siouxland Hematology-Oncology Associates, LLP
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Rcca Md,Llc
  • New York
    • Hawthorne, New York, United States, 10532
      • Hudson Valley Hematology and Oncology Associates
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State Milton S. Hershey Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
    • Houston, Texas, United States, 77030
      • The University of Texas, MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Only subjects previously participating in two specific studies are eligible to enroll into this study. Enrollment is not open to subjects if not previously enrolled in studies B1871006 or B1871008.

Exclusion Criteria:

• All subjects are excluded unless previously participating in studies B1871006 or B1871008.

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Based on National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 3.0)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was any untoward medical occurrence at any dose that: resulted in death, was life threatening (immediate risk of death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions), resulted in congenital anomaly/birth defect. Treatment-emergent adverse events were defined as any event increasing in severity from baseline or any new event started during bosutinib therapy or within 30 days of the last dose of study drug.	From first dose of drug up to 30 days after last dose (up to approximately 14 years)
Number of Participants With Grade 3 or 4 Treatment-Emergent Adverse Events (AEs) Based on National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 3.0)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs were assessed according to severity grading based on NCI CTCAE version 3.0. Grade 1 =mild; Grade 2 =moderate; Grade 3 =severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4 =life-threatening or disabling, urgent intervention indicated; Grade 5 =death. Treatment-emergent adverse events were defined as any event increasing in severity from baseline or any new event started during bosutinib therapy or within 30 days of the last dose of study drug.	From first dose of drug up to 30 days after last dose (up to approximately 14 years)
Number of Participants With Treatment-Emergent Treatment Related Adverse Events (AEs) Based on National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 3.0)	An AE was any untoward medical occurrence in a participant who received study drug. Treatment-emergent adverse events were defined as any event increasing in severity from baseline or any new event started during bosutinib therapy or within 30 days of the last dose of study drug. Related TEAEs were those AEs who were related to the study treatment as judged by the investigator.	From first dose of drug up to 30 days after last dose (up to approximately 14 years)
Number of Participants With Laboratory Test Abnormalities Based on National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03)	Laboratory parameters included Chemistry: high alkaline phosphatase; high alanine aminotransferase; high aspartate aminotransferase; high blood bilirubin; high creatinine. Hematology: absolute neutrophils count decreased; anemia; platelet count decreased; white blood cells (WBC) decreased. Abnormalities in laboratory tests were graded per NCI CTCAE version 4.03 as Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling.	From first dose of drug up to 30 days after last dose (up to approximately 14 years)
Number of Participants With Adverse Events as Reason for Treatment Discontinuation	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.	From first dose of drug up to 30 days after last dose (up to approximately 14 years)
Number of Participants With Diarrhea After Switch From Bosutinib Clinical Formulation to Bosutinib Commercial Formulation	The incidence of diarrhea was collected and analyzed before and after the switch from the clinical formulation of bosutinib to the commercial formulation of bosutinib.	Last 6 months on clinical formulation and first 6 months on commercial formulation
Number of Participants With Breakpoint Cluster Region Abelson Protooncogene (BCR-ABL) Mutations Present at Time of Bosutinib Treatment Discontinuation	BCR-ABL is a gene resulting from the 9:22 chromosomal translocation (Philadelphia chromosome). In this outcome measure, the number of participants who had emergent mutation or new BCR-ABL mutations (participants who had a post-baseline mutation which was not present at baseline) were reported.	Post-baseline on Day 1 (maximum up to 14 years)
Overall Survival (OS) Rate at Year 10	OS was defined as the time from randomization (B1871008) and time from first dose (B1871006) to the occurrence of death due to any cause or censoring. Kaplan-Meier analysis was used for determination of OS. Percentage of participants who were alive were estimated in this outcome measure.	Year 10
Plasma Steady-State Trough Concentrations (Ctrough) of Bosutinib	Ctrough refers to plasma concentration of bosutinib observed just before treatment administration.	One pre-dose sample was collected at the first scheduled visit (after approval and implementation of protocol amendment 1) following at least 2 weeks of uninterrupted dosing at the same dose level
Kaplan-Meier Estimate of Probability of Maintaining Major Cytogenetic Response (MCyR) at Year 10: B1871006 Participants	Cytogenetic response (CyR) is based on prevalence of Ph+ cells. Duration for MCyR: time from first response to confirmed loss, progression of disease, or on-treatment death due to any cause, or censoring analyzed for responders only. Confirmed loss was defined as 2 consecutive non-responses at least 28 days apart. MCyR was categorized as either complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR). Response was achieved when there was 0% (CCyR) or 1-35% (PCyR) Ph+ cells analyzed from conventional cytogenetics based on the analysis of 20 to 100 metaphases or <1% (CCyR) or 1-35% (PCyR) Ph+ cells analyzed from fluorescence in-situ hybridization (FISH) based on analysis of at least 200 nuclei. CCyR may be imputed on a specific date if an MMR or better is achieved and denoted on the CRF on that date for B1871040 study visits. The Kaplan-Meier analysis was used to analyze percentage of participants maintaining MCyR at Year 10.	Year 10
Kaplan-Meier Estimate of Probability of Maintaining Complete Cytogenetic Response (CCyR) at Year 10: B1871006 Participants	Duration for CCyR was defined as time from first response to confirmed loss, progression of disease, or on-treatment death due to any cause, or censoring analyzed for responders only. Confirmed loss was defined as 2 consecutive assessments with >0 Ph+ metaphases or >=1% positive cells from FISH at least 28 days apart or progression or death. CCyR was achieved when there was 0% Ph+ cells analysed from conventional cytogenetics with 20 to 100 metaphases or <1% Ph+ cells analysed from FISH with at least 200 nuclei. CCyR may be imputed on a specific date if MMR or better is achieved and denoted on the CRF on that date for B1871040 study visits. The Kaplan-Meier analysis was used to analyze percentage of participants maintaining CCyR at Year 10.	Year 10
Kaplan-Meier Estimate of Probability of Maintaining Complete Hematologic Response (CHR) at Year 10: B1871006 Participants	Duration for CHR was defined as time from first response to confirmed loss, progression of disease, or on-treatment death due to any cause, or censoring analyzed for responders only. Confirmed loss was defined as 2 consecutive non-responses at least 14 days apart. Complete hematologic response was considered when participants met all of the following criteria: White blood cells equal to or less than (<=) institutional upper limit of normal (ULN), no blasts or promyelocytes in blood, <20% basophils in blood, no extramedullary involvement (including hepatomegaly or splenomegaly), myelocytes and metamyelocytes <5% in blood, platelets <450*10^9 per liter (/L). The following were applicable only to advanced phase: <=5% bone marrow blasts, absolute neutrophil count >=1.0*10^9/L, platelets >=100*10^9/L. The Kaplan-Meier analysis was used to analyze percentage of participants maintaining CHR at Year 10.	Year 10
Cumulative Incidence of Progression/Death Events at Year 10: B1871006 Participants	Progression free survival (PFS):interval from date of first dose of bosutinib in parent study until earlier date of progression or death from any cause. Participants without events censored at last evaluation date. PD:evolution from CP (or return to CP for ADV participants) to AP or BP (on 2 consecutive assessments at least 1 week apart), evolution from AP to BP (on 2 consecutive assessments at least 1 week apart) and one of following conditions occurred after dose escalation or presence of AEs prohibiting dose escalation: for 2nd or later line, loss of MCyR (need at least 30% increase); for all lines of treatment, loss of CHR confirmed by 2 assessments >=2 weeks apart; for all lines of treatment, increasing WBC defined as doubling of WBC over a period of >=1 month with second WBC >20*10^9/L confirmed at least 1 week later. Percentage of participants with PFS/death events based on cumulative incidence method adjusting for competing event of treatment discontinuation without event.	Year 10
Cumulative Incidence of Rate of Transformation to Accelerated Phase (AP) or Blast Phase (BP) at Year 10: B1871006 Participants	Time to transformation was defined as the time from first dose in the parent study to the first date of confirmed transformation to AP or BP. Confirmed transformation was defined as 2 consecutive assessments at least 1 week apart or 1 assessment confirmed by progression of disease or death. For participants without transformation, censorship was at the last evaluation date. Percentage of participants with time to transformation to AP/BP was reported based on cumulative incidence method adjusting for the competing risk of treatment discontinuation without the event.	Year 10

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Takahashi N, Cortes JE, Sakaida E, Ishizawa K, Ono T, Doki N, Matsumura I, Garcia-Gutierrez V, Rosti G, Ono C, Ohkura M, Tanetsugu Y, Viqueira A, Brummendorf TH. Safety profile of bosutinib in Japanese versus non-Japanese patients with chronic myeloid leukemia: a pooled analysis. Int J Hematol. 2022 Jun;115(6):838-851. doi: 10.1007/s12185-022-03314-y. Epub 2022 Mar 2.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2013
• Primary Completion (Actual): June 5, 2020
• Study Completion (Actual): June 5, 2020

Study Registration Dates

• First Submitted: July 16, 2013
• First Submitted That Met QC Criteria: July 16, 2013
• First Posted (Estimate): July 19, 2013

Study Record Updates

• Last Update Posted (Actual): July 19, 2022
• Last Update Submitted That Met QC Criteria: June 28, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Subjects; Extension; Chronic Myeloid Leukemia; CML; Bosutinib
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Other Study ID Numbers: B1871040; 2013-000691-15 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.