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

Chronic Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01903733
• Other study ID #: B1871040
• Secondary ID: 2013-000691-15
• Status: Completed
• Phase: N/A
• Start date: August 28, 2013
• Est. completion date: June 5, 2020

Study information

• Verified date: June 2022
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 281
• Est. completion date: June 5, 2020
• Est. primary completion date: June 5, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• bosutinib
The starting bosutinib dose is 500 mg once daily, however the dose can vary from 300 mg to 600 mg.

Locations

Country	Name	City	State
Argentina	Instituto Medico Especializado Alexander Fleming	Cd. Autonoma De Buenos Aires	Buenos Aires
Argentina	Hospital Dr. Jose Ramon Vidal	Corrientes
Argentina	Hospital Italiano de la Plata	La Plata	Buenos Aires
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Royal Brisbane & Women's Hospital	Herston	Queensland
Belgium	GHDC (Grand Hopital de Charleroi)	Charleroi
Brazil	Universidade Estadual de Campinas / Centro de Hematologia e Hemoterapia	Campinas	SP
Brazil	Faculdade de Medicina do ABC - Centro de Estudos e Pesquisa em Hematologia e Oncologia (CEPHO)	Santo Andre	SP
Canada	Alberta Health Services - Department of Medical Oncology - Cross Cancer Institute	Edmonton	Alberta
Canada	Sir Mortimer B. Davis-Jewish General Hospital	Montreal	Quebec
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
Chile	Instituto Oncologico	Renaca	V Region
Chile	Instituto Oncologico, Clinica Renaca	Renaca	V Region
China	Chinese People's Liberation Army General Hospital	Beijing
China	Peking Union Medical College Hospital	Beijing	Beijing
China	The First affiliated Hospital of College of Medicine, Zhejiang University	Hangzhou	Zhejiang
China	Ruijin Hospital- Shanghai Jiaotong University School of Medicine	Shanghai
China	Blood Disease Hospital, Chinese Academy of Medical Science & Peking Union Medical College	Tianjin
Colombia	Fundacion Santa Fe de Bogota	Bogota	Cundinamarca
Finland	Helsingin Yliopistollinen Keskussairaala, Hematologian poliklinikka	Helsinki
France	CHU de CAEN	Caen Cedex 9
France	CHU Hotel Dieu - Service Hematologie	Nantes cedex 1
France	CHU Poitiers	Poitiers
France	CHU de Poitiers	Poitiers Cedex
France	Strasbourg Oncologie Liberale -Centre de Radiotherapie, Clinique Ste Anne	Strasbourg
Hong Kong	Pamela Youde Nethersole Eastern Hospital	Chai Wan
Hong Kong	Department of Medicine & Therapeutics, Prince of Wales Hospital	Shatin, New Territories
Hungary	Egyesitett Szent Istvan es Szent Laszlo Korhaz-Rendelointezet	Budapest
Hungary	Somogy Megyei Kaposi Mor Oktato Korhaz, Belgyogyaszati Osztaly	Kaposvar
India	Christian Medical College. Vellore	Vellore	Tamil NADU
Italy	A.O.U. Policlinico S.Orsola Malpighi	Bologna	BO
Italy	ASST Monza - Ospedale san Gerardo	Monza	Monza AND Brianza
Italy	A.O.U. San Luigi Gonzaga di Orbassano	Orbassano	TO
Italy	Ospedale S. Eugenio - UOC Ematologia	Roma
Japan	Akita University Hospital	Akita City	Akita
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka-shi	Fukuoka
Japan	Hamamatsu University School of Medicine University Hospital	Hamamatsu-shi	Shizuoka
Japan	Kanazawa University Hospital	Kanazawa-shi	Ishikawa
Japan	Kindai University Hospital	Osakasayama-city	Osaka
Japan	Osaka University Hospital	Suita-city	Osaka
Japan	Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital	Tokyo
Japan	Toyohashi Municipal Hospital	Toyohashi	Aichi
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul
Latvia	Riga East Clinical University Hospital	Riga
Netherlands	VU University Medical Center	Amsterdam
Netherlands	University Medical Center Groningen, Department of Hematology	Groningen
Peru	Unidad de Investigacion de Hematologia - Hospital Nacional Edgardo Rebagliati Martins	Lima
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	SP ZOZ Szpital Uniwersytecki w Krakowie	Krakow
Poland	Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie	Lublin
Russian Federation	State Budgetary Institution of Healthcare of Sverdlovsk Region	Ekaterinburg	Sverdlovsk Region
Russian Federation	Federal State-Funded Institution National Research Center of Hematology of the Ministry of	Moscow
Russian Federation	State Budgetary Educational Institution of Higher Professional Education	Rostov-on-Don
Russian Federation	State Budgetary Institution of Rostov Region - Rostov Regional Clinical Hospital	Rostov-on-Don
Russian Federation	Clinic "Institute of Pediatric Oncology, Hematology and Transplantation n.a. R.M. Gorbachova"	Saint Petersburg
Russian Federation	Federal State Budgetary Institution "Federal Almazov Medical Research Centre"	Saint Petersburg
Russian Federation	State Budgetary Institution of Healthcare - Leningrad Regional Clinical Hospital	Saint Petersburg
Russian Federation	State Budgetary Institution of Healthcare Samara Regional Clinical Hospital n.a. V.D. Seredavin	Samara
Singapore	Singapore General Hospital	Singapore
South Africa	Wits Clinical Research-Chris Hani Baragwanath Hospital	Soweto	Gauteng
Spain	Hospital Clinic Barcelona	Barcelona
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario La Princesa	Madrid
Spain	Hospital Universitario Madrid Sanchinarro, Centro Integral Oncologico Clara Campal	Madrid
Spain	Hospital Virgen de la Salud	Toledo
Spain	Hospital Clinico Universitario De Valencia (CHUV)	Valencia
Thailand	Division of Hematology, Department of Medicine, Faculty of Medicine, Siriraj Hospital,	Bangkok
Turkey	Hacettepe Universitesi Tip Fakultesi	Ankara
Turkey	Gaziantep Universitesi Tip Fakultesi Sahinbey Uygulama ve Arastirma Hastanesi	Gaziantep	Sehit Kamil
Ukraine	Municipal Institution "Cherkasy Regional Oncology Dispensary"	Cherkasy
Ukraine	MI "Dnipropetrovsk City Multi-field Clinical Hospital #4" of DRC Hematology Center	Dnipropetrovsk
Ukraine	Kyiv City Clinical Hospital #9, SI "Institute of Hematology and Transfusiology of NAMS of Ukraine"	Kyiv
Ukraine	State Institution "National Research Center for Radiation Medicine of the National Academy of	Kyiv
Ukraine	State Institution "Institute of Blood Pathology and Transfusion Medicine of	Lviv
United Kingdom	Freeman Hospital	Newcastle Upon Tyne
United Kingdom	Nottingham University Hospitals NHS Trust	Nottinhgam
United States	Emory University Hospital	Atlanta	Georgia
United States	Northside Hospital Inc., - GCS/Northside	Atlanta	Georgia
United States	Northside Hospital, Inc. - Central Research Department	Atlanta	Georgia
United States	The Emory Clinic	Atlanta	Georgia
United States	Winship Cancer Institute, Emory University	Atlanta	Georgia
United States	Rcca Md,Llc	Bethesda	Maryland
United States	Hudson Valley Hematology and Oncology Associates	Hawthorne	New York
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
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	Indiana Blood and Marrow Transplantation	Indianapolis	Indiana
United States	Orlando Health, Inc	Orlando	Florida
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  Chile,  China,  Colombia,  Finland,  France,  Hong Kong,  Hungary,  India,  Italy,  Japan,  Korea, Republic of,  Latvia,  Netherlands,  Peru,  Poland,  Russian Federation,  Singapore,  South Africa,  Spain,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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
Primary	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)
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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

External Links

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