Bosutinib Treatment Extension Study Only For Subjects With Chronic Myeloid Leukemia (CML) Who Have Previously Participated In Bosutinib Studies B1871006 Or B1871008
- Conditions
- Chronic Myeloid Leukemia
- Registration Number
- NCT01903733
- Lead Sponsor
- Pfizer
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 281
- 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.
- All subjects are excluded unless previously participating in studies B1871006 or B1871008.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Primary Outcome Measures
Name Time Method Number of Participants With Adverse Events as Reason for Treatment Discontinuation From first dose of drug up to 30 days after last dose (up to approximately 14 years) An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
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) From first dose of drug up to 30 days after last dose (up to approximately 14 years) 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.
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) From first dose of drug up to 30 days after last dose (up to approximately 14 years) 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.
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) From first dose of drug up to 30 days after last dose (up to approximately 14 years) 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.
Number of Participants With Laboratory Test Abnormalities Based on National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) From first dose of drug up to 30 days after last dose (up to approximately 14 years) 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.
Number of Participants With Diarrhea After Switch From Bosutinib Clinical Formulation to Bosutinib Commercial Formulation Last 6 months on clinical formulation and first 6 months on 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.
Number of Participants With Breakpoint Cluster Region Abelson Protooncogene (BCR-ABL) Mutations Present at Time of Bosutinib Treatment Discontinuation Post-baseline on Day 1 (maximum up to 14 years) 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.
Overall Survival (OS) Rate at Year 10 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.
Plasma Steady-State Trough Concentrations (Ctrough) of Bosutinib 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 Ctrough refers to plasma concentration of bosutinib observed just before treatment administration.
Cumulative Incidence of Progression/Death Events at Year 10: B1871006 Participants Year 10 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.
Cumulative Incidence of Rate of Transformation to Accelerated Phase (AP) or Blast Phase (BP) at Year 10: B1871006 Participants Year 10 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.
Kaplan-Meier Estimate of Probability of Maintaining Complete Cytogenetic Response (CCyR) at Year 10: B1871006 Participants Year 10 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.
Kaplan-Meier Estimate of Probability of Maintaining Major Cytogenetic Response (MCyR) at Year 10: B1871006 Participants Year 10 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.
Kaplan-Meier Estimate of Probability of Maintaining Complete Hematologic Response (CHR) at Year 10: B1871006 Participants Year 10 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.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (90)
Hospital Italiano de la Plata
🇦🇷La Plata, Buenos Aires, Argentina
CHU de CAEN
🇫🇷Caen Cedex 9, France
ASST Monza - Ospedale san Gerardo
🇮🇹Monza, Monza AND Brianza, Italy
Toyohashi Municipal Hospital
🇯🇵Toyohashi, Aichi, Japan
Osaka University Hospital
🇯🇵Suita-city, Osaka, Japan
GHDC (Grand Hopital de Charleroi)
🇧🇪Charleroi, Belgium
Instituto Oncologico, Clinica Renaca
🇨🇱Renaca, V Region, Chile
Instituto Oncologico
🇨🇱Renaca, V Region, Chile
CHU de Poitiers
🇫🇷Poitiers Cedex, France
Ospedale S. Eugenio - UOC Ematologia
🇮🇹Roma, Italy
CHU Hotel Dieu - Service Hematologie
🇫🇷Nantes cedex 1, France
Faculdade de Medicina do ABC - Centro de Estudos e Pesquisa em Hematologia e Oncologia (CEPHO)
🇧🇷Santo Andre, SP, Brazil
Pamela Youde Nethersole Eastern Hospital
🇭🇰Chai Wan, Hong Kong
Division of Hematology, Department of Medicine, Faculty of Medicine, Siriraj Hospital,
🇹🇭Bangkok, Thailand
MI "Dnipropetrovsk City Multi-field Clinical Hospital #4" of DRC Hematology Center
🇺🇦Dnipropetrovsk, Ukraine
State Institution "National Research Center for Radiation Medicine of the National Academy of
🇺🇦Kyiv, Ukraine
Orlando Health, Inc
🇺🇸Orlando, Florida, United States
Universidade Estadual de Campinas / Centro de Hematologia e Hemoterapia
🇧🇷Campinas, SP, Brazil
Strasbourg Oncologie Liberale -Centre de Radiotherapie, Clinique Ste Anne
🇫🇷Strasbourg, France
A.O.U. Policlinico S.Orsola Malpighi
🇮🇹Bologna, BO, Italy
A.O.U. San Luigi Gonzaga di Orbassano
🇮🇹Orbassano, TO, Italy
National Hospital Organization Kyushu Cancer Center
🇯🇵Fukuoka-shi, Fukuoka, Japan
Kanazawa University Hospital
🇯🇵Kanazawa-shi, Ishikawa, Japan
University Medical Center Groningen, Department of Hematology
🇳🇱Groningen, Netherlands
Gaziantep Universitesi Tip Fakultesi Sahinbey Uygulama ve Arastirma Hastanesi
🇹🇷Gaziantep, Sehit Kamil, Turkey
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Helsingin Yliopistollinen Keskussairaala, Hematologian poliklinikka
🇫🇮Helsinki, Finland
Unidad de Investigacion de Hematologia - Hospital Nacional Edgardo Rebagliati Martins
🇵🇪Lima, Peru
SP ZOZ Szpital Uniwersytecki w Krakowie
🇵🇱Krakow, Poland
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdańsk, Poland
Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
🇵🇱Lublin, Poland
Federal State Budgetary Institution "Federal Almazov Medical Research Centre"
🇷🇺Saint Petersburg, Russian Federation
Municipal Institution "Cherkasy Regional Oncology Dispensary"
🇺🇦Cherkasy, Ukraine
Kyiv City Clinical Hospital #9, SI "Institute of Hematology and Transfusiology of NAMS of Ukraine"
🇺🇦Kyiv, Ukraine
State Institution "Institute of Blood Pathology and Transfusion Medicine of
🇺🇦Lviv, Ukraine
Emory University Hospital
🇺🇸Atlanta, Georgia, United States
The Emory Clinic
🇺🇸Atlanta, Georgia, United States
Indiana Blood and Marrow Transplantation
🇺🇸Indianapolis, Indiana, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
The University of Texas, MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Winship Cancer Institute, Emory University
🇺🇸Atlanta, Georgia, United States
Hudson Valley Hematology and Oncology Associates
🇺🇸Hawthorne, New York, United States
Northside Hospital, Inc. - Central Research Department
🇺🇸Atlanta, Georgia, United States
Instituto Medico Especializado Alexander Fleming
🇦🇷Cd. Autonoma De Buenos Aires, Buenos Aires, Argentina
Penn State Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Northside Hospital Inc., - GCS/Northside
🇺🇸Atlanta, Georgia, United States
Rcca Md,Llc
🇺🇸Bethesda, Maryland, United States
Hospital Dr. Jose Ramon Vidal
🇦🇷Corrientes, Argentina
Royal Brisbane & Women's Hospital
🇦🇺Herston, Queensland, Australia
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Vancouver General Hospital
🇨🇦Vancouver, British Columbia, Canada
Ruijin Hospital- Shanghai Jiaotong University School of Medicine
🇨🇳Shanghai, China
Fundacion Santa Fe de Bogota
🇨🇴Bogota, Cundinamarca, Colombia
Hospital Clinic Barcelona
🇪🇸Barcelona, Spain
Clinic "Institute of Pediatric Oncology, Hematology and Transplantation n.a. R.M. Gorbachova"
🇷🇺Saint Petersburg, Russian Federation
Christian Medical College. Vellore
🇮🇳Vellore, Tamil NADU, India
Egyesitett Szent Istvan es Szent Laszlo Korhaz-Rendelointezet
🇭🇺Budapest, Hungary
Hacettepe Universitesi Tip Fakultesi
🇹🇷Ankara, Turkey
Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital
🇯🇵Tokyo, Japan
Riga East Clinical University Hospital
🇱🇻Riga, Latvia
Wits Clinical Research-Chris Hani Baragwanath Hospital
🇿🇦Soweto, Gauteng, South Africa
State Budgetary Educational Institution of Higher Professional Education
🇷🇺Rostov-on-Don, Russian Federation
State Budgetary Institution of Healthcare - Leningrad Regional Clinical Hospital
🇷🇺Saint Petersburg, Russian Federation
Freeman Hospital
🇬🇧Newcastle Upon Tyne, United Kingdom
Hospital Universitario La Princesa
🇪🇸Madrid, Spain
State Budgetary Institution of Healthcare Samara Regional Clinical Hospital n.a. V.D. Seredavin
🇷🇺Samara, Russian Federation
Singapore General Hospital
🇸🇬Singapore, Singapore
Hospital Virgen de la Salud
🇪🇸Toledo, Spain
Nottingham University Hospitals NHS Trust
🇬🇧Nottinhgam, United Kingdom
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Universitario Madrid Sanchinarro, Centro Integral Oncologico Clara Campal
🇪🇸Madrid, Spain
Hospital Clinico Universitario De Valencia (CHUV)
🇪🇸Valencia, Spain
Somogy Megyei Kaposi Mor Oktato Korhaz, Belgyogyaszati Osztaly
🇭🇺Kaposvar, Hungary
Siouxland Hematology-Oncology Associates, LLP
🇺🇸Sioux City, Iowa, United States
Alberta Health Services - Department of Medical Oncology - Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
Sir Mortimer B. Davis-Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
Peking Union Medical College Hospital
🇨🇳Beijing, Beijing, China
The First affiliated Hospital of College of Medicine, Zhejiang University
🇨🇳Hangzhou, Zhejiang, China
Chinese People's Liberation Army General Hospital
🇨🇳Beijing, China
Blood Disease Hospital, Chinese Academy of Medical Science & Peking Union Medical College
🇨🇳Tianjin, China
CHU Poitiers
🇫🇷Poitiers, France
Akita University Hospital
🇯🇵Akita City, Akita, Japan
Kindai University Hospital
🇯🇵Osakasayama-city, Osaka, Japan
Hamamatsu University School of Medicine University Hospital
🇯🇵Hamamatsu-shi, Shizuoka, Japan
The Catholic University of Korea, Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
VU University Medical Center
🇳🇱Amsterdam, Netherlands
State Budgetary Institution of Healthcare of Sverdlovsk Region
🇷🇺Ekaterinburg, Sverdlovsk Region, Russian Federation
State Budgetary Institution of Rostov Region - Rostov Regional Clinical Hospital
🇷🇺Rostov-on-Don, Russian Federation
Federal State-Funded Institution National Research Center of Hematology of the Ministry of
🇷🇺Moscow, Russian Federation
Department of Medicine & Therapeutics, Prince of Wales Hospital
🇭🇰Shatin, New Territories, Hong Kong