--- title: Safety And Efficacy Study Of Bosutinib In Patients With Philadelphia Chromosome Positive Chronic Myeloid Leukemia Previously Treated With One Or More Tyrosine Kinase Inhibitors nct_id: NCT02228382 overall_status: TERMINATED phase: PHASE4 sponsor: Pfizer study_type: INTERVENTIONAL primary_condition: Previously Treated PH + CML countries: United States, Austria, France, Germany, Italy, Norway, Spain, Sweden canonical_url: "https://parkinsonspathways.com/agent/trials/NCT02228382.md" clinicaltrials_gov: "https://clinicaltrials.gov/study/NCT02228382" ct_last_update_post_date: 2021-12-30 last_seen_at: "2026-05-12T06:10:40.998Z" source: ClinicalTrials.gov (mirrored, no enrichment) --- # 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 **NCT ID:** [NCT02228382](https://clinicaltrials.gov/study/NCT02228382) ## Key Facts - **Status:** TERMINATED - **Phase:** PHASE4 - **Study Type:** INTERVENTIONAL - **Target Enrollment:** 163 - **Lead Sponsor:** Pfizer - **Collaborators:** Developmental Therapeutics Consortium - **Conditions:** Previously Treated PH + CML - **Start Date:** 2014-11-07 - **Completion Date:** 2020-10-13 - **CT.gov Last Update:** 2021-12-30 ## 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 - **Minimum age:** 18 Years - **Sex:** ALL - **Healthy Volunteers:** No ``` 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. ``` ## Arms - **Bosutinib** (EXPERIMENTAL) ## Interventions - **Bosutinib** (DRUG) — 100 mg and 500 mg tablets, once daily dosage up to 4 years duration ## Primary Outcomes - **Percentage of Participants With Cumulative Confirmed Major Cytogenetic Response (MCyR) in 2nd and 3rd Line Chronic Phase (CP) Participants** _(time frame: Up to 1 year (52 weeks))_ — Confirmed MCyR: confirmed (complete cytogenetic response\[CCyR\] or partial cytogenetic response\[PCyR\]) by 1 year for participants entering the study without CCyR or maintenance of confirmed CCyR for at least 1 year after treatment start with bosutinib for participants entering the study with CCyR or at least major molecular response(MMR) by 1 year and a deeper molecular response compared to baseline. Participants with baseline PCyR that did not achieve CCyR were counted as nonresponders. Initial cytogenetic (in absence of MMR) responses must have been confirmed by 2 consecutive assessments \>=28 days apart. CCyR: 0% Ph+ cells from \>=20 metaphases from conventional cytogenetics or \<1% Ph+ cells from \>= 200 cells from fluorescent in situ hybridization(FISH). PCyR: 1 to 35% Ph+ cells. MMR: \<=0.1% BCR-ABL1 on the international scale (IS) with at least 10,000 ABL1 transcripts assessed by central laboratory. - **Percentage of Participants With Cumulative Confirmed Major Cytogenetic Response (MCyR) in 4th or Later Line Chronic Phase (CP) Participants** _(time frame: Up to 1 year (52 weeks))_ — Confirmed MCyR: confirmed CCyR or PCyR by 1 year for participants entering the study without CCyR or maintenance of confirmed CCyR for at least 1 year after treatment start with bosutinib for participants entering the study with CCyR or at least MMR by 1 year and a deeper molecular response compared to baseline. Participants with baseline PCyR that did not achieve CCyR were counted as nonresponders. Initial cytogenetic (in absence of MMR) responses must have been confirmed by 2 consecutive assessments \>=28 days apart. CCyR: 0% Ph+ cells from \>=20 metaphases from conventional cytogenetics or \<1% Ph+ cells from \>= 200 cells from fluorescent in situ hybridization(FISH). PCyR: 1 to 35% Ph+ cells. MMR: \<=0.1% BCR-ABL1 on the IS with at least 10,000 ABL1 transcripts assessed by central laboratory. - **Percentage of Participants With Cumulative Confirmed Overall Hematological Response (OHR) in Accelerated Phase (AP) Chronic Myelogenous Leukemia (CML) Participants** _(time frame: Up to 1 year (52 weeks))_ — Confirmed OHR was defined as complete hematological response (CHR) or return to chronic phase (RCP) by 1 year in AP and BP participants. CHR was defined as white blood cells (WBC) \<10\*10\^9/L, peripheral blood basophils \<5%, no peripheral blood myelocytes, promyelocytes, myeloblasts in the differential, platelet count \<450\*10\^9/L, spleen not palpable. Hematologic responses must be of \>=4 weeks duration confirmed by 2 assessments \>=4 weeks apart. ## Secondary Outcomes - **Percentage of Participants With Cumulative Major Cytogenetic Response (MCyR)** _(time frame: Up to 4 years)_ - **Percentage of Participants With Cumulative Confirmed Overall Hematological Response (OHR) in Participants With Accelerated Phase (AP) Chronic Myelogenous Leukemia (CML)** _(time frame: Up to 4 years)_ - **Percentage of Participants With Cumulative Best Response** _(time frame: Up to 4 years)_ - **Percentage of Participants With Major Cytogenetic Response (MCyR) at Months 3, 6, 12, 18 and 24** _(time frame: Months 3, 6, 12, 18, and 24)_ - **Percentage of Accelerated Phase Participants With Confirmed Overall Hematological Response (OHR) at Month 3, 6, 9, 12, 18, and 24** _(time frame: Months 3, 6, 9, 12, 18, and 24)_ - **Percentage of Participants With Cumulative Confirmed Complete Hematological Response (CHR)** _(time frame: Up to 4 years)_ - **Percentage of Participants With Cumulative Major Molecular Response (MMR)** _(time frame: Up to 4 years)_ - **Kaplan-Meier Estimate of Probability of Retaining Complete Cytogenetic Response (CCyR) at Month 36** _(time frame: At Month 36)_ - **Kaplan-Meier Estimate of Probability of Retaining Major Molecular Response (MMR) at Month 36** _(time frame: At Month 36)_ - **Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious AEs** _(time frame: First dose of study drug up to 28 days after last dose (up to maximum of 4 years))_ - **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** _(time frame: First dose of study drug up to 28 days after last dose (up to maximum of 4 years))_ - **Number of Participants With Treatment Related Treatment Emergent Adverse Events (TEAEs)** _(time frame: First dose of study drug up to 28 days after last dose (up to maximum of 4 years))_ - **Number of Participants With Laboratory Abnormalities Based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03** _(time frame: First dose of study drug up to 28 days after last dose (up to maximum of 4 years))_ ## Locations (48) - Keck Hospital of USC, Los Angeles, California, United States - LAC+USC Medical Center, Los Angeles, California, United States - USC/Norris Comprehensive Cancer Center, Los Angeles, California, United States - Sylvester Deerfield Beach, Deerfield Beach, Florida, United States - University of Miami Hospital & Clinics, Miami, Florida, United States - Indiana Blood and Marrow Transplantation-Clinic, Indianapolis, Indiana, United States - Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, United States - Siteman Cancer Center - West County, Creve Coeur, Missouri, United States - Barnes-Jewish Hospital, St Louis, Missouri, United States - Washington University School of Medicine, St Louis, Missouri, United States - Siteman Cancer Center - South County, St Louis, Missouri, United States - Weill Cornell Medical College - New York-Presbyterian Hospital, New York, New York, United States - Seattle Cancer Care Alliance, Seattle, Washington, United States - Medizinische Universitaet Innsbruck, Innsbruck, Austria - Ordensklinikum Linz Gmbh Barmherzige Schwestern, Linz, Austria - Institut Bergonie, Bordeaux, France - Centre Hospitalier de Versailles (CHV)-Hopital Andre Mignot Service d'Hematologie Clinique- Oncology, Le Chesnay, France - Centre Regional De Lutte Contre Le Cancer, Marseille, France - Hopital Archet I, Nice, France - Institut Universitaire du Cancer Toulouse - Oncopole, Toulouse, France - CHU Brabois, Vandœuvre-lès-Nancy, France - RWTH Uniklinik Aachen Klinik fur Onkologie, Hamatologie und Stammzelltransplantation, Aachen, Germany - Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum (CVK), Berlin, Germany - Universitaetsklinikum Koeln (AoeR), Cologne, Germany - Universitaetsklinikum Hamburg-Eppendorf, Hamburg, Germany - Klinik fur Innere Medizin II, Jena, Germany - III. Medizinische Klinik Universitaetsmedizin Mannheim, Mannheim, Germany - AOU Policlinico Consorziale di Bari - UO Ematologia con Trapianto, Bari, BA, Italy - A.O.U. Policlinico S. Orsola-Malpighi, Bologna, BO, Italy - Azienda Socio Sanitaria Territoriale - ASST Monza, Monza, MB, Italy - Ospedale S. Eugenio - UOC Ematologia, Rome, RM, Italy - AOU San Luigi Gonzaga SCDU Medicina Interna II ad indirizzo Ematologico, Orbassano, TO, Italy - AOU Policlinico Vittorio Emanuele-P.O.G. Rodolico, Catania, Italy - SOD Ematologia, Florence, Italy - A.O. Ospedale Niguarda Ca Granda - SC Ematologia, Milan, Italy - Haukeland Universitetssjukehus, Bergen, Norway - St Olav Hospital, Trondheim, Norway - Hospital Universitario Quiron Madrid, Pozuelo de Alarcón, Madrid, Spain - Hospital Universitari Vall d' Hebron, Barcelona, Spain - Hospital Universitari Vall d'Hebron, Barcelona, Spain - Hospital Clinic De Barcelona, Barcelona, Spain - Hospital Universitario de La Princesa, Madrid, Spain - Hospital Universitario Ramon y Cajal, Madrid, Spain - Hospital Clinico Universitario de Salamanca, Salamanca, Spain - Hospital Universitari i Politecnic La Fe de Valencia, Valencia, Spain - Hospital de dia Quiron Zaragoza, Zaragoza, Spain - Hematologiskt centrum, Stockholm, Sweden - Akademiska Sjukhuset, Uppsala, Sweden ## Recent Field Changes (last 30 days) - `locations.indiana blood and marrow transplantation-clinic|indianapolis|indiana|united states` — added _(2026-05-12)_ - `status.overallStatus` — added _(2026-05-12)_ - `status.primaryCompletionDate` — added _(2026-05-12)_ - 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`locations.university of miami hospital & clinics|miami|florida|united states` — added _(2026-05-12)_ - `locations.sidney kimmel comprehensive cancer center at johns hopkins|baltimore|maryland|united states` — added _(2026-05-12)_ - `locations.siteman cancer center - west county|creve coeur|missouri|united states` — added _(2026-05-12)_ - `locations.barnes-jewish hospital|st louis|missouri|united states` — added _(2026-05-12)_ - `locations.washington university school of medicine|st louis|missouri|united states` — added _(2026-05-12)_ - `locations.siteman cancer center - south county|st louis|missouri|united states` — added _(2026-05-12)_ - `locations.weill cornell medical college - new york-presbyterian hospital|new york|new york|united states` — added _(2026-05-12)_ - `locations.seattle cancer care alliance|seattle|washington|united states` — added _(2026-05-12)_ - `locations.medizinische universitaet innsbruck|innsbruck||austria` — added _(2026-05-12)_ - `locations.ordensklinikum linz gmbh barmherzige schwestern|linz||austria` — added _(2026-05-12)_ - `locations.institut bergonie|bordeaux||france` — added _(2026-05-12)_ - `locations.centre hospitalier de versailles (chv)-hopital andre mignot service d'hematologie clinique- oncology|le chesnay||france` — added _(2026-05-12)_ - `locations.centre regional de lutte contre le cancer|marseille||france` — added _(2026-05-12)_ - `locations.hopital archet i|nice||france` — added _(2026-05-12)_ - `locations.institut universitaire du cancer toulouse - oncopole|toulouse||france` — added _(2026-05-12)_ - `locations.chu brabois|vandœuvre-lès-nancy||france` — added _(2026-05-12)_ - `locations.rwth uniklinik aachen klinik fur onkologie, hamatologie und stammzelltransplantation|aachen||germany` — added _(2026-05-12)_ - `locations.charite - universitaetsmedizin berlin - campus virchow-klinikum (cvk)|berlin||germany` — added _(2026-05-12)_ - `locations.universitaetsklinikum koeln (aoer)|cologne||germany` — added _(2026-05-12)_ - `locations.universitaetsklinikum hamburg-eppendorf|hamburg||germany` — added _(2026-05-12)_ - `locations.klinik fur innere medizin ii|jena||germany` — added _(2026-05-12)_ - `locations.iii. medizinische klinik universitaetsmedizin mannheim|mannheim||germany` — added _(2026-05-12)_ - `locations.aou policlinico consorziale di bari - uo ematologia con trapianto|bari|ba|italy` — added _(2026-05-12)_ - `locations.a.o.u. policlinico s. orsola-malpighi|bologna|bo|italy` — added _(2026-05-12)_ - `locations.azienda socio sanitaria territoriale - asst monza|monza|mb|italy` — added _(2026-05-12)_ - `locations.ospedale s. eugenio - uoc ematologia|rome|rm|italy` — added _(2026-05-12)_ - `locations.aou san luigi gonzaga scdu medicina interna ii ad indirizzo ematologico|orbassano|to|italy` — added _(2026-05-12)_ - `locations.aou policlinico vittorio emanuele-p.o.g. rodolico|catania||italy` — added _(2026-05-12)_ - `locations.sod ematologia|florence||italy` — added _(2026-05-12)_ --- *Canonical: https://parkinsonspathways.com/agent/trials/NCT02228382.md* *Source data (authoritative): https://clinicaltrials.gov/study/NCT02228382* *This page is a raw mirror with no AI summary, no editorial enrichment, and no Parkinson's-specific filtering.*