Previously Treated PH + CMLPhase 4NCT02228382
Safety And Efficacy Study Of Bosutinib In Patients With Philadelphia Chromosome Positive Chronic Myeloid Leukemia Previously Treated With One Or More Tyrosine Kinase Inhibitors
A Phase 4 study testing Bosutinib in people with Previously Treated PH + CML, run by Pfizer at 48 sites in 8 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Previously Treated PH + CML
- What is being tested?
- Bosutinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 163 participants
- Where
- 48 sitesin 8 countries
- Study dates
- 7 Nov 2014to 13 Oct 2020
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
48 sites in 8 countries.
48 sites in 8 countries
United States13 sites
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21287
Siteman Cancer Center - West County
Creve Coeur, Missouri, 63141-6337
Sylvester Deerfield Beach
Deerfield Beach, Florida, 33442
Indiana Blood and Marrow Transplantation-Clinic
Indianapolis, Indiana, 46237
Keck Hospital of USC
Los Angeles, California, 90033
LAC+USC Medical Center
Los Angeles, California, 90033
USC/Norris Comprehensive Cancer Center
Los Angeles, California, 90033
University of Miami Hospital & Clinics
Miami, Florida, 33136
Weill Cornell Medical College - New York-Presbyterian Hospital
New York, New York, 10021
Seattle Cancer Care Alliance
Seattle, Washington, 98109
Barnes-Jewish Hospital
St Louis, Missouri, 63110
Washington University School of Medicine
St Louis, Missouri, 63110
Siteman Cancer Center - South County
St Louis, Missouri, 63129
Spain9 sites
Hospital Universitari Vall d' Hebron
Barcelona, 08035
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Hospital Clinic De Barcelona
Barcelona, 08036
Hospital Universitario de La Princesa
Madrid, 28006
Hospital Universitario Ramon y Cajal
Madrid, 28034
Hospital Universitario Quiron Madrid
Pozuelo de Alarcón, Madrid, 28223
Hospital Clinico Universitario de Salamanca
Salamanca, 37007
Hospital Universitari i Politecnic La Fe de Valencia
Valencia, 46026
Hospital de dia Quiron Zaragoza
Zaragoza, 50012
Italy8 sites
AOU Policlinico Consorziale di Bari - UO Ematologia con Trapianto
Bari, BA, 70124
A.O.U. Policlinico S. Orsola-Malpighi
Bologna, BO, 40138
AOU Policlinico Vittorio Emanuele-P.O.G. Rodolico
Catania, 95123
SOD Ematologia
Florence, 50134
A.O. Ospedale Niguarda Ca Granda - SC Ematologia
Milan, 20162
Azienda Socio Sanitaria Territoriale - ASST Monza
Monza, MB, 20900
AOU San Luigi Gonzaga SCDU Medicina Interna II ad indirizzo Ematologico
Orbassano, TO, 10043
Ospedale S. Eugenio - UOC Ematologia
Rome, RM, 00144
France6 sites
Institut Bergonie
Bordeaux, 33076
Centre Hospitalier de Versailles (CHV)-Hopital Andre Mignot Service d'Hematologie Clinique- Oncology
Le Chesnay, 78157
Centre Regional De Lutte Contre Le Cancer
Marseille, 13009
Hopital Archet I
Nice, 06202
Institut Universitaire du Cancer Toulouse - Oncopole
Toulouse, 31059
CHU Brabois
Vandœuvre-lès-Nancy, 54511
Germany6 sites
RWTH Uniklinik Aachen Klinik fur Onkologie, Hamatologie und Stammzelltransplantation
Aachen, 52074
Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum (CVK)
Berlin, 13353
Universitaetsklinikum Koeln (AoeR)
Cologne, 50937
Universitaetsklinikum Hamburg-Eppendorf
Hamburg, 20246
Klinik fur Innere Medizin II
Jena, 07747
III. Medizinische Klinik Universitaetsmedizin Mannheim
Mannheim, D-68167
Austria2 sites
Medizinische Universitaet Innsbruck
Innsbruck, 6020
Ordensklinikum Linz Gmbh Barmherzige Schwestern
Linz, 4010
Norway2 sites
Haukeland Universitetssjukehus
Bergen, 5021
St Olav Hospital
Trondheim, 7030
Sweden2 sites
Hematologiskt centrum
Stockholm, 171 76
Akademiska Sjukhuset
Uppsala, 751 85
About this study
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
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).
- Conditions
- Previously Treated PH + CML
- Being tested
- Bosutinib
- Keywords
- Bosutinib, Chronic Myeloid Leukemia, CML, Leukemia, Myelogenous, Chronic, BC-ABL Positive
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BosutinibDrug
Also called BOSULIF
100 mg and 500 mg tablets, once daily dosage up to 4 years duration
| Study group | Role | What they receive |
|---|---|---|
| Bosutinib | Experimental | Not described Receives: Drug: Bosutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Cumulative Confirmed Major Cytogenetic Response (MCyR) in 2nd and 3rd Line Chronic Phase (CP) Participants
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.
Measured: Up to 1 year (52 weeks)
Percentage of Participants With Cumulative Confirmed Major Cytogenetic Response (MCyR) in 4th or Later Line Chronic Phase (CP) Participants
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.
Measured: Up to 1 year (52 weeks)
Percentage of Participants With Cumulative Confirmed Overall Hematological Response (OHR) in Accelerated Phase (AP) Chronic Myelogenous Leukemia (CML) Participants
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.
Measured: Up to 1 year (52 weeks)
Secondary outcomes (13)
Percentage of Participants With Cumulative Major Cytogenetic Response (MCyR)
CyR was based on prevalence of Ph+ cells. CCyR was achieved when there was 0 % Ph+ cells from >=20 metaphases from conventional bone marrow cytogenetics or <1% Ph+ cells from >=200 cells analyzed from FISH. PCyR was achieved when 1 to 35% Ph+ cells were present. MCyR was categorized as either CCyR or PCyR. Participants with MMR or better at baseline were counted as CCyR if baseline response was maintained or improved while on treatment.
Measured: Up to 4 years
Percentage of Participants With Cumulative Confirmed Overall Hematological Response (OHR) in Participants With Accelerated Phase (AP) Chronic Myelogenous Leukemia (CML)
Confirmed OHR was defined as CHR or RCP in AP and BP participants. CHR was defined as 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.
Measured: Up to 4 years
Percentage of Participants With Cumulative Best Response
Hierarchy best response: %participants with best response among molecular/cytogenetic/hematologic response. Molecular response:MR4.5/MR4/MMR defined as <=0.0032/0.01/0.1% BCR-ABL1 ratio on IS corresponding to >=4.5/4/3-log reduction from standardised baseline with at least 32,000/10,000/10,000 ABL1 assessed by central laboratory. CyR:based on prevalence of Ph+cells. CCyR: 0% Ph+cells from >=20 metaphases from conventional cytogenetics or <1%Ph+cells from >=200 cells from FISH. PCyR:1 to 35% Ph+cells. CHR:WBC <10*10^9/L, peripheral blood basophils<5%, no peripheral blood myelocytes, promyelocytes, myeloblasts in differential, platelet count<450*10^9/L, spleen not palpable.
Measured: Up to 4 years
Percentage of Participants With Major Cytogenetic Response (MCyR) at Months 3, 6, 12, 18 and 24
CyR was based on prevalence of Ph+ cells. CCyR was achieved when there was 0 % Ph+ cells from >=20 metaphases from conventional bone marrow cytogenetics or <1% Ph+ cells from >=200 cells analyzed from FISH. PCyR was achieved when 1 to 35% Ph+ cells were present. MCyR was categorized as either CCyR or PCyR. Participants with MMR or better at baseline were counted as CCyR if baseline response was maintained or improved while on treatment.
Measured: 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
Confirmed OHR was defined as CHR or RCP in AP and BP participants. CHR was defined as 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.
Measured: Months 3, 6, 9, 12, 18, and 24
Percentage of Participants With Cumulative Confirmed Complete Hematological Response (CHR)
CHR was defined as 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.
Measured: Up to 4 years
Percentage of Participants With Cumulative Major Molecular Response (MMR)
Molecular response: MR4.5/MR4/MMR defined as <=0.0032/0.01/0.1% BCR-ABL1 ratio respectively, on IS corresponding to >=4.5/4/3-log reduction from standardized baseline with at least 32,000/10,000/10,000 ABL1 assessed by central laboratory. To be considered a responder, the participant must have had maintenance of baseline response while on-treatment or an improvement from baseline.
Measured: Up to 4 years
Kaplan-Meier Estimate of Probability of Retaining Complete Cytogenetic Response (CCyR) at Month 36
Kaplan-Meier analysis. Duration of CCyR: from first date of CCyR to date of confirmed loss of CCyR/disease progression/on-treatment death or censoring, analyzed for responders only. CyR: prevalence of Ph+ cells. CCyR: 0% Ph+ cells from >=20 metaphases from conventional cytogenetics or <1% Ph+ cells from >=200 cells analyzed by FISH or MMR (<=0.1% BCR-ABL1 on the IS with at least 10,000 ABL1 transcripts assessed by central laboratory). Confirmed loss: 2 consecutive non-response assessments >=28 days apart. Progression: for CP: participants evolving from CP to AP, loss of CHR; loss of MCyR; in participants without CHR WBC >20*10^9/L on 2 occasions >=2 weeks apart after the first 4 weeks of treatment; for AP: confirmed BP, loss of previous hematologic response over a 2-week period, loss of CHR, no decrease from baseline levels (if considered clinically relevant) in percentage blasts in peripheral blood or bone marrow on all assessments over a 4-week period.
Measured: At Month 36
Kaplan-Meier Estimate of Probability of Retaining Major Molecular Response (MMR) at Month 36
Kaplan-Meier analysis. Duration of MMR: from first date of MMR to confirmed loss of MMR/disease progression/on-treatment death or censoring, analyzed for responders only. MMR:<=0.1% BCR-ABL1 on the IS with at least 10,000 ABL1 transcripts assessed by central laboratory . Confirmed loss: 2 consecutive non-response assessments >=28 days apart with a <3-log (>0.1%) reduction in transcripts one of which corresponds to a <=2-log reduction (>=1%). Progression: for CP: participants evolving from CP to AP, loss of CHR; loss of MCyR; in participants without CHR WBC >20*10^9/L on 2 occasions >=2weeks apart after the first 4 weeks of treatment; for AP: confirmed BP, loss of previous hematologic response over a 2-week period, loss of CHR, no decrease from baseline levels (if considered clinically relevant) in percentage blasts in peripheral blood or bone marrow on all assessments over a 4-week period.
Measured: At Month 36
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious AEs
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAE: any event increasing in severity from baseline or any new event started during bosutinib therapy or within 28 days of the last dose of study drug. SAE: an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial/prolonged inpatient hospitalization; life-threatening experience (immediate risk of death); persistent or significant disability/incapacity; congenital anomaly.
Measured: 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
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAE was any event increasing in severity from baseline or any new event that started during bosutinib therapy or within 28 days of the last dose of study drug. Severity was graded as Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. Number of participants with Grade 3 or 4 TEAEs are reported.
Measured: 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)
An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. TEAE was any event increasing in severity from baseline or any new event that started during bosutinib therapy or within 28 days of the last dose of study drug. Relatedness to drug was assessed by investigator.
Measured: 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
Number of participants with any hematological, chemistry and coagulation abnormality of any grade were reported. Hematological: absolute neutrophil count (low), hemoglobin (low), lymphocytes (low), platelets (low) and leukocytes (low). Chemistry: alkaline phosphatase (high), alanine aminotransferase (high), amylase (high), aspartate aminotransferase (high), bilirubin (high), creatinine (high), lipase (high). Coagulation: activated partial prothrombin time (low), prothrombin time (low and high), partial prothrombin time (high).
Measured: First dose of study drug up to 28 days after last dose (up to maximum of 4 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2014 (estimated)
- Study start7 Nov 2014
- Primary completion13 Oct 2020
- Study completion13 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Previously Treated PH + CMLStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Masking
- None (open label)
- Enrolment
- 163 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Developmental Therapeutics Consortium
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02228382
- Sponsor's protocol ID
- B1871039
- Other IDs
- 2013-003250-25, BYOND
- Status last verified
- Dec 2021
- First submitted
- 27 Aug 2014
- Last updated
- 30 Dec 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: 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.
Publications
Gambacorti-Passerini C, Brummendorf TH, Abruzzese E, Kelly KR, Oehler VG, Garcia-Gutierrez V, Hjorth-Hansen H, Ernst T, Leip E, Purcell S, Luscan G, Viqueira A, Giles FJ, Hochhaus A. Efficacy and safety of bosutinib in previously treated patients with chronic myeloid leukemia: final results from the BYOND trial. Leukemia. 2024 Oct;38(10):2162-2170. doi: 10.1038/s41375-024-02372-x. Epub 2024 Aug 20.
PubMed 39164407Smith BD, Brummendorf TH, Roboz GJ, Gambacorti-Passerini C, Charbonnier A, Viqueira A, Leip E, Purcell S, Goldman EH, Giles F, Ernst T, Hochhaus A, Rosti G. Efficacy and safety of bosutinib in patients treated with prior imatinib and/or dasatinib and/or nilotinib: Subgroup analyses from the phase 4 BYOND study. Leuk Res. 2024 Apr;139:107481. doi: 10.1016/j.leukres.2024.107481. Epub 2024 Mar 11.
PubMed 38484432Rosti G, Brummendorf TH, Gjertsen BT, Giraldo-Castellano P, Castagnetti F, Gambacorti-Passerini C, Ernst T, Zhao H, Kuttschreuter L, Purcell S, Giles FJ, Hochhaus A. Impact of age and comorbidities on the efficacy and tolerability of bosutinib in previously treated patients with chronic myeloid leukemia: results from the phase 4 BYOND study. Leukemia. 2024 Jan;38(1):126-135. doi: 10.1038/s41375-023-02080-y. Epub 2023 Nov 25.
PubMed 38007586Takahashi 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.
PubMed 35235189Hochhaus 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.
PubMed 32572189
Study at a glance
From the registry record, last updated by the sponsor on 30 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02228382
- Acronym / sponsor ID
- B1871039
- Conditions
- Previously Treated PH + CML
- Keywords
- Bosutinib, Chronic Myeloid Leukemia, CML, Leukemia, Myelogenous, Chronic, BC-ABL Positive
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 163 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Collaborators
- Developmental Therapeutics Consortium
- Study start
- 7 Nov 2014 (actual)
- Primary completion
- 13 Oct 2020 (actual)
- Study completion
- 13 Oct 2020 (actual)
- First posted
- 29 Aug 2014 (estimated)
- Results
- Posted 30 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bosutinib | Experimental | Drug: Bosutinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BosutinibAlso: BOSULIF100 mg and 500 mg tablets, once daily dosage up to 4 years duration | Drug | Bosutinib |
Primary outcome
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.
13 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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Dec 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39164407Gambacorti-Passerini C, Brummendorf TH, Abruzzese E, Kelly KR, Oehler VG, Garcia-Gutierrez V, Hjorth-Hansen H, Ernst T, Leip E, Purcell S, Luscan G, Viqueira A, Giles FJ, Hochhaus A. Efficacy and safety of bosutinib in previously treated patients with chronic myeloid leukemia: final results from the BYOND trial. Leukemia. 2024 Oct;38(10):2162-2170. doi: 10.1038/s41375-024-02372-x. Epub 2024 Aug 20.
- Derived from this study: PubMed 38484432Smith BD, Brummendorf TH, Roboz GJ, Gambacorti-Passerini C, Charbonnier A, Viqueira A, Leip E, Purcell S, Goldman EH, Giles F, Ernst T, Hochhaus A, Rosti G. Efficacy and safety of bosutinib in patients treated with prior imatinib and/or dasatinib and/or nilotinib: Subgroup analyses from the phase 4 BYOND study. Leuk Res. 2024 Apr;139:107481. doi: 10.1016/j.leukres.2024.107481. Epub 2024 Mar 11.
- Derived from this study: PubMed 38007586Rosti G, Brummendorf TH, Gjertsen BT, Giraldo-Castellano P, Castagnetti F, Gambacorti-Passerini C, Ernst T, Zhao H, Kuttschreuter L, Purcell S, Giles FJ, Hochhaus A. Impact of age and comorbidities on the efficacy and tolerability of bosutinib in previously treated patients with chronic myeloid leukemia: results from the phase 4 BYOND study. Leukemia. 2024 Jan;38(1):126-135. doi: 10.1038/s41375-023-02080-y. Epub 2023 Nov 25.
- Derived from this study: PubMed 35235189Takahashi 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.
- Derived from this study: PubMed 32572189Hochhaus 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.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
Related trials for Previously Treated PH + CML
Not yet recruitingPhase 3
A Randomized Study of ELVN-001 Versus Investigator-Selected TKI, in CP-CML Previously Treated With One or More TKIs
Chronic Myeloid Leukemia (CML), Chronic Myeloid Leukemia (CML) Philadelphia Chromosome Positive
RecruitingPhase 2
Study to Determine the Efficacy and Safety of Asciminib in Pediatric Patients With Ph+ CML-CP
Chronic Myelogenous Leukemia, Leukemia, Myelogenous, Chronic, Philadelphia Chromosome Positive
RecruitingPhase 1/2
Study to Determine the Dose and Safety of Asciminib in Pediatric Patients With Chronic Myeloid Leukemia
Myeloid Leukemia, Philadelphia Positive
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
48 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Bosutinib in people with Previously Treated PH + CML, run by Pfizer at 48 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 30 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 48 sites in United States, Spain, Italy, France, Germany and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02228382, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Dec 2021.