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
2 other identifiers
interventional
281
29 countries
91
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Aug 2013
Longer than P75 for not_applicable
91 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 16, 2013
CompletedFirst Posted
Study publicly available on registry
July 19, 2013
CompletedStudy Start
First participant enrolled
August 28, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 5, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
June 5, 2020
CompletedResults Posted
Study results publicly available
August 17, 2021
CompletedJuly 19, 2022
June 1, 2022
6.8 years
July 16, 2013
June 7, 2021
June 28, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (14)
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
Interventions
The starting bosutinib dose is 500 mg once daily, however the dose can vary from 300 mg to 600 mg.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- All subjects are excluded unless previously participating in studies B1871006 or B1871008.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Pfizerlead
Study Sites (91)
Orlando Health, Inc
Orlando, Florida, 32806, United States
Emory University Hospital
Atlanta, Georgia, 30322, United States
The Emory Clinic
Atlanta, Georgia, 30322, United States
Winship Cancer Institute, Emory University
Atlanta, Georgia, 30322, United States
Northside Hospital Inc., - GCS/Northside
Atlanta, Georgia, 30342, United States
Northside Hospital, Inc. - Central Research Department
Atlanta, Georgia, 30342, United States
Indiana Blood and Marrow Transplantation
Indianapolis, Indiana, 46237, United States
Siouxland Hematology-Oncology Associates, LLP
Sioux City, Iowa, 51101, United States
Rcca Md,Llc
Bethesda, Maryland, 20817, United States
Hudson Valley Hematology and Oncology Associates
Hawthorne, New York, 10532, United States
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033-0850, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
The University of Texas, MD Anderson Cancer Center
Houston, Texas, 77030, United States
Instituto Medico Especializado Alexander Fleming
Cd. Autonoma de Buenos Aires, Buenos Aires, C1426ANZ, Argentina
Hospital Italiano de la Plata
La Plata, Buenos Aires, 1900, Argentina
Hospital Dr. Jose Ramon Vidal
Corrientes, 3400, Argentina
Royal Brisbane & Women's Hospital
Herston, Queensland, 4029, Australia
Royal Adelaide Hospital
Adelaide, South Australia, 5000, Australia
GHDC (Grand Hopital de Charleroi)
Charleroi, 6000, Belgium
Universidade Estadual de Campinas / Centro de Hematologia e Hemoterapia
Campinas, São Paulo, 13083-878, Brazil
Faculdade de Medicina do ABC - Centro de Estudos e Pesquisa em Hematologia e Oncologia (CEPHO)
Santo André, São Paulo, 09060-650, Brazil
Alberta Health Services - Department of Medical Oncology - Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2, Canada
Vancouver General Hospital
Vancouver, British Columbia, V5Z1M9, Canada
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9, Canada
Sir Mortimer B. Davis-Jewish General Hospital
Montreal, Quebec, H3T 1E2, Canada
Instituto Oncologico, Clinica Renaca
Reñaca, Región de Valparaíso, 2540364, Chile
Instituto Oncologico
Reñaca, Región de Valparaíso, 2540488, Chile
Peking Union Medical College Hospital
Beijing, Beijing Municipality, 100730, China
The First affiliated Hospital of College of Medicine, Zhejiang University
Hangzhou, Zhejiang, 310003, China
Chinese People's Liberation Army General Hospital
Beijing, 100853, China
Ruijin Hospital- Shanghai Jiaotong University School of Medicine
Shanghai, 200025, China
Blood Disease Hospital, Chinese Academy of Medical Science & Peking Union Medical College
Tianjin, 300020, China
Fundacion Santa Fe de Bogota
Bogota, Cundinamarca, 110111, Colombia
Helsingin Yliopistollinen Keskussairaala, Hematologian poliklinikka
Helsinki, 00290, Finland
CHU de CAEN
Caen, 14033, France
CHU Hotel Dieu - Service Hematologie
Nantes, 44093, France
CHU de Poitiers
Poitiers, 86021, France
CHU Poitiers
Poitiers, 86021, France
Strasbourg Oncologie Liberale -Centre de Radiotherapie, Clinique Ste Anne
Strasbourg, 67000, France
Pamela Youde Nethersole Eastern Hospital
Chai Wan, Hong Kong
Department of Medicine & Therapeutics, Prince of Wales Hospital
Shatin, New Territories, Hong Kong
Egyesitett Szent Istvan es Szent Laszlo Korhaz-Rendelointezet
Budapest, 1097, Hungary
Somogy Megyei Kaposi Mor Oktato Korhaz, Belgyogyaszati Osztaly
Kaposvár, 7400, Hungary
Christian Medical College. Vellore
Vellore, Tamil Nadu, 632004, India
A.O.U. Policlinico S.Orsola Malpighi
Bologna, BO, 40138, Italy
ASST Monza - Ospedale san Gerardo
Monza, Monza and Brianza, 20090, Italy
A.O.U. San Luigi Gonzaga di Orbassano
Orbassano, TO, 10043, Italy
Ospedale S. Eugenio - UOC Ematologia
Roma, 00144, Italy
Toyohashi Municipal Hospital
Toyohashi, Aichi-ken, 4418570, Japan
Akita University Hospital
Akita, Akita, 010-8543, Japan
National Hospital Organization Kyushu Cancer Center
Fukuoka, Fukuoka, 811-1395, Japan
Kanazawa University Hospital
Kanazawa, Ishikawa-ken, 920-8641, Japan
Kindai University Hospital
Sayama, Osaka, 589-8511, Japan
Osaka University Hospital
Suita, Osaka, 565-0871, Japan
Hamamatsu University School of Medicine University Hospital
Hamamatsu, Shizuoka, 431-3192, Japan
Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital
Tokyo, 113-8677, Japan
Riga East Clinical University Hospital
Riga, LV-1079, Latvia
VU University Medical Center
Amsterdam, 1081 HV, Netherlands
University Medical Center Groningen, Department of Hematology
Groningen, 9713 GZ, Netherlands
Unidad de Investigacion de Hematologia - Hospital Nacional Edgardo Rebagliati Martins
Lima, 11, Peru
Uniwersyteckie Centrum Kliniczne
Gdansk, 80-214, Poland
Uniwersyteckie Centrum Kliniczne
Gdansk, 80-952, Poland
SP ZOZ Szpital Uniwersytecki w Krakowie
Krakow, 31-501, Poland
Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
Lublin, 20-081, Poland
State Budgetary Institution of Healthcare of Sverdlovsk Region
Yekaterinburg, Sverdlovsk Oblast, 620102, Russia
Federal State-Funded Institution National Research Center of Hematology of the Ministry of
Moscow, 125167, Russia
State Budgetary Institution of Rostov Region - Rostov Regional Clinical Hospital
Rostov-on-Don, 344015, Russia
State Budgetary Educational Institution of Higher Professional Education
Rostov-on-Don, 344022, Russia
State Budgetary Institution of Healthcare - Leningrad Regional Clinical Hospital
Saint Petersburg, 194291, Russia
Clinic "Institute of Pediatric Oncology, Hematology and Transplantation n.a. R.M. Gorbachova"
Saint Petersburg, 197022, Russia
Federal State Budgetary Institution "Federal Almazov Medical Research Centre"
Saint Petersburg, 197341, Russia
State Budgetary Institution of Healthcare Samara Regional Clinical Hospital n.a. V.D. Seredavin
Samara, 443095, Russia
Singapore General Hospital
Singapore, 169608, Singapore
Wits Clinical Research-Chris Hani Baragwanath Hospital
Soweto, Gauteng, 2013, South Africa
The Catholic University of Korea, Seoul St. Mary's Hospital
Seoul, 06591, South Korea
Hospital Clinic Barcelona
Barcelona, 08036, Spain
Hospital Universitario La Princesa
Madrid, 28006, Spain
Hospital Universitario La Paz
Madrid, 28046, Spain
Hospital Universitario Madrid Sanchinarro, Centro Integral Oncologico Clara Campal
Madrid, 28050, Spain
Hospital Virgen de la Salud
Toledo, 45004, Spain
Hospital Clinico Universitario De Valencia (CHUV)
Valencia, 46010, Spain
Division of Hematology, Department of Medicine, Faculty of Medicine, Siriraj Hospital,
Bangkok, 10700, Thailand
Gaziantep Universitesi Tip Fakultesi Sahinbey Uygulama ve Arastirma Hastanesi
Gaziantep, Sehit Kamil, 27310, Turkey (Türkiye)
Hacettepe Universitesi Tip Fakultesi
Ankara, 06100, Turkey (Türkiye)
Municipal Institution "Cherkasy Regional Oncology Dispensary"
Cherkasy, 18009, Ukraine
MI "Dnipropetrovsk City Multi-field Clinical Hospital #4" of DRC Hematology Center
Dnipropetrovsk, 49102, Ukraine
State Institution "National Research Center for Radiation Medicine of the National Academy of
Kyiv, 03115, Ukraine
Kyiv City Clinical Hospital #9, SI "Institute of Hematology and Transfusiology of NAMS of Ukraine"
Kyiv, 04112, Ukraine
State Institution "Institute of Blood Pathology and Transfusion Medicine of
Lviv, 79044, Ukraine
Freeman Hospital
Newcastle upon Tyne, NE7 7DN, United Kingdom
Nottingham University Hospitals NHS Trust
Nottinhgam, NG5 1PB, United Kingdom
Related Publications (1)
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.
PMID: 35235189DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Pfizer ClinicalTrials.gov Call Center
- Organization
- Pfizer Inc.
Study Officials
- STUDY DIRECTOR
Pfizer CT.gov Call Center
Pfizer
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NA
- Masking
- NONE
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 16, 2013
First Posted
July 19, 2013
Study Start
August 28, 2013
Primary Completion
June 5, 2020
Study Completion
June 5, 2020
Last Updated
July 19, 2022
Results First Posted
August 17, 2021
Record last verified: 2022-06
Data Sharing
- IPD Sharing
- Will not share
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.