Clinical trial NCT02228382: Safety And Efficacy Study Of Bosutinib In Patients With Philadelphia Chromosome Positive Chronic Myeloid Leukemia Previously Treated With One Or More Tyrosine Kinase Inhibitors
Official title: A PHASE 4 SAFETY AND EFFICACY STUDY OF BOSUTINIB (BOSULIF (REGISTERED)) IN PATIENTS WITH PHILADELPHIA CHROMOSOME POSITIVE CHRONIC MYELOID LEUKEMIA PREVIOUSLY TREATED WITH ONE OR MORE TYROSINE KINASE INHIBITORS
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Previously Treated PH + CML
Keywords: Bosutinib
Chronic Myeloid Leukemia
CML
Leukemia
Myelogenous
Chronic
BC-ABL Positive
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Developmental Therapeutics Consortium
First posted: 2014-08-29
Enrollment: 163
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to fulfill the post-authorization commitment made by Pfizer to the European Medicines Agency in providing additional safety and efficacy data in approximately 150 Philadelphia Chromosome Positive Chronic Myeloid Leukemia patients with high unmet medical need, including 75 Chronic Phase, Accelerated Phase or Blast Phase patients in the fourth or later line treatment setting (i.e., after treatment with at least 3 other Tyrosine Kinase Inhibitors).


Eligibility criteria: Inclusion Criteria:

* Confirmed Philadelphia Chromosome positive Chronic Myeloid Leukemia or Confirmed BCR-ABL1 (Abelson-break point cluster) Positive if Philadelphia Chromosome negative Chronic Myeloid Leukemia (from initial diagnosis).
* Prior treatment with 1 or more tyrosine kinase inhibitor drugs (imatinib, dasatinib and/or nilotinib) for Philadelphia Chromosome positive Chronic Myeloid Leukemia (CML).
* Any Chronic Myeloid Leukemia disease phase, as long as the patient is unable to receive treatment with imatinib, dasatinib and/or nilotinib for any reason.

Exclusion Criteria:

* Participation in any other clinical studies involving investigational drug(s) within 14 days or within 3 half-lives of drug levels in blood (whichever is longer) prior to the first dose of bosutinib.
* Prior treatment with bosutinib.
* Prior treatment with ponatinib.
* Known T315I or V299L mutation.

Primary outcomes:
measure: Percentage of Participants With Cumulative Confirmed Major Cytogenetic Response (MCyR) in 2nd and 3rd Line Chronic Phase (CP) Participants
timeFrame: Up to 1 year (52 weeks)
measure: Percentage of Participants With Cumulative Confirmed Major Cytogenetic Response (MCyR) in 4th or Later Line Chronic Phase (CP) Participants
timeFrame: Up to 1 year (52 weeks)
measure: Percentage of Participants With Cumulative Confirmed Overall Hematological Response (OHR) in Accelerated Phase (AP) Chronic Myelogenous Leukemia (CML) Participants
timeFrame: Up to 1 year (52 weeks)
Secondary outcomes:
measure: Percentage of Participants With Cumulative Major Cytogenetic Response (MCyR)
timeFrame: Up to 4 years
measure: Percentage of Participants With Cumulative Confirmed Overall Hematological Response (OHR) in Participants With Accelerated Phase (AP) Chronic Myelogenous Leukemia (CML)
timeFrame: Up to 4 years
measure: Percentage of Participants With Cumulative Best Response
timeFrame: Up to 4 years
measure: Percentage of Participants With Major Cytogenetic Response (MCyR) at Months 3, 6, 12, 18 and 24
timeFrame: Months 3, 6, 12, 18, and 24
measure: Percentage of Accelerated Phase Participants With Confirmed Overall Hematological Response (OHR) at Month 3, 6, 9, 12, 18, and 24
timeFrame: Months 3, 6, 9, 12, 18, and 24
measure: Percentage of Participants With Cumulative Confirmed Complete Hematological Response (CHR)
timeFrame: Up to 4 years
measure: Percentage of Participants With Cumulative Major Molecular Response (MMR)
timeFrame: Up to 4 years
measure: Kaplan-Meier Estimate of Probability of Retaining Complete Cytogenetic Response (CCyR) at Month 36
timeFrame: At Month 36
measure: Kaplan-Meier Estimate of Probability of Retaining Major Molecular Response (MMR) at Month 36
timeFrame: At Month 36
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious AEs
timeFrame: First dose of study drug up to 28 days after last dose (up to maximum of 4 years)
measure: Number of Participants With Grade 3 or 4 Treatment Emergent Adverse Events (TEAEs) Based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
timeFrame: First dose of study drug up to 28 days after last dose (up to maximum of 4 years)
measure: Number of Participants With Treatment Related Treatment Emergent Adverse Events (TEAEs)
timeFrame: First dose of study drug up to 28 days after last dose (up to maximum of 4 years)
measure: Number of Participants With Laboratory Abnormalities Based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03
timeFrame: First dose of study drug up to 28 days after last dose (up to maximum of 4 years)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Keck Hospital of USC
state: California
city: Los Angeles
country: United States
facility: LAC+USC Medical Center
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: Deerfield Beach
country: United States
facility: Sylvester Deerfield Beach
state: Florida
city: Miami
country: United States
facility: University of Miami Hospital & Clinics
state: Florida
city: Indianapolis
country: United States
facility: Indiana Blood and Marrow Transplantation-Clinic
state: Indiana
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Creve Coeur
country: United States
facility: Siteman Cancer Center - West County
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center - South County
state: Missouri
city: New York
country: United States
facility: Weill Cornell Medical College - New York-Presbyterian Hospital
state: New York
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Innsbruck
country: Austria
facility: Medizinische Universitaet Innsbruck
city: Linz
country: Austria
facility: Ordensklinikum Linz Gmbh Barmherzige Schwestern
city: Bordeaux Cedex 09
country: France
facility: Institut Bergonie
city: Le Chesnay Cedex
country: France
facility: Centre Hospitalier de Versailles (CHV)-Hopital Andre Mignot Service d'Hematologie Clinique- Oncology
city: Marseille
country: France
facility: Centre Regional De Lutte Contre Le Cancer
city: Nice Cedex 3
country: France
facility: Hopital Archet I
city: Toulouse Cedex 9
country: France
facility: Institut Universitaire du Cancer Toulouse - Oncopole
city: Vandoeuvre-les-Nancy cedex
country: France
facility: CHU Brabois
city: Aachen
country: Germany
facility: RWTH Uniklinik Aachen Klinik fur Onkologie, Hamatologie und Stammzelltransplantation
city: Berlin
country: Germany
facility: Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum (CVK)
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf
city: Jena
country: Germany
facility: Klinik fur Innere Medizin II
city: Koeln
country: Germany
facility: Universitaetsklinikum Koeln (AoeR)
city: Mannheim
country: Germany
facility: III. Medizinische Klinik Universitaetsmedizin Mannheim
city: Bari
country: Italy
facility: AOU Policlinico Consorziale di Bari - UO Ematologia con Trapianto
state: BA
city: Bologna
country: Italy
facility: A.O.U. Policlinico S. Orsola-Malpighi
state: BO
city: Monza
country: Italy
facility: Azienda Socio Sanitaria Territoriale - ASST Monza
state: MB
city: Rome
country: Italy
facility: Ospedale S. Eugenio - UOC Ematologia
state: RM
city: Orbassano
country: Italy
facility: AOU San Luigi Gonzaga SCDU Medicina Interna II ad indirizzo Ematologico
state: TO
city: Catania
country: Italy
facility: AOU Policlinico Vittorio Emanuele-P.O.G. Rodolico
city: Firenze
country: Italy
facility: SOD Ematologia
city: Milano
country: Italy
facility: A.O. Ospedale Niguarda Ca Granda - SC Ematologia
city: Bergen
country: Norway
facility: Haukeland Universitetssjukehus
city: Trondheim
country: Norway
facility: St Olav Hospital
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Universitario Quiron Madrid
state: Madrid
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d' Hebron
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic De Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario de La Princesa
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: Zaragoza
country: Spain
facility: Hospital de dia Quiron Zaragoza
city: Stockholm
country: Sweden
facility: Hematologiskt centrum
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Hochhaus A, Gambacorti-Passerini C, Abboud C, Gjertsen BT, Brummendorf TH, Smith BD, Ernst T, Giraldo-Castellano P, Olsson-Stromberg U, Saussele S, Bardy-Bouxin N, Viqueira A, Leip E, Russell-Smith TA, Leone J, Rosti G, Watts J, Giles FJ; BYOND Study Investigators. Bosutinib for pretreated patients with chronic phase chronic myeloid leukemia: primary results of the phase 4 BYOND study. Leukemia. 2020 Aug;34(8):2125-2137. doi: 10.1038/s41375-020-0915-9. Epub 2020 Jun 22.