Safety And Efficacy Study Of Bosutinib In Patients With Philadelphia Chromosome Positive Chronic Myeloid Leukemia Previously Treated With One Or More Tyrosine Kinase Inhibitors

NCT02228382 | Terminated Phase 4 Results

• 3 other identifiers: B18710392013-003250-25BYOND
• Study Type: interventional
• Target: 163
• Locations: 8 countries
• Sites: 48

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).

Conditions

Previously Treated PH + CML

Keywords

Bosutinib; Chronic Myeloid Leukemia; CML; Leukemia; Myelogenous; Chronic; BC-ABL Positive

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  Up to 1 year (52 weeks)

Secondary Outcomes (13)

• Percentage of Participants With Cumulative Major Cytogenetic Response (MCyR)

  Up to 4 years

• Percentage of Participants With Cumulative Confirmed Overall Hematological Response (OHR) in Participants With Accelerated Phase (AP) Chronic Myelogenous Leukemia (CML)

  Up to 4 years

• Percentage of Participants With Cumulative Best Response

  Up to 4 years

• Percentage of Participants With Major Cytogenetic Response (MCyR) at Months 3, 6, 12, 18 and 24

  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

  Months 3, 6, 9, 12, 18, and 24

Study Arms (1)

Bosutinib

EXPERIMENTAL

Drug: Bosutinib

Interventions

Bosutinib DRUG

100 mg and 500 mg tablets, once daily dosage up to 4 years duration

Also known as: BOSULIF

Bosutinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead
• Developmental Therapeutics Consortium: collaborator

Study Sites (48)

Keck Hospital of USC

Los Angeles, California, 90033, United States

Location

LAC+USC Medical Center

Los Angeles, California, 90033, United States

Location

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Sylvester Deerfield Beach

Deerfield Beach, Florida, 33442, United States

Location

University of Miami Hospital & Clinics

Miami, Florida, 33136, United States

Location

Indiana Blood and Marrow Transplantation-Clinic

Indianapolis, Indiana, 46237, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

Siteman Cancer Center - West County

Creve Coeur, Missouri, 63141-6337, United States

Location

Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Siteman Cancer Center - South County

St Louis, Missouri, 63129, United States

Location

Weill Cornell Medical College - New York-Presbyterian Hospital

New York, New York, 10021, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Medizinische Universitaet Innsbruck

Innsbruck, 6020, Austria

Location

Ordensklinikum Linz Gmbh Barmherzige Schwestern

Linz, 4010, Austria

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Centre Hospitalier de Versailles (CHV)-Hopital Andre Mignot Service d'Hematologie Clinique- Oncology

Le Chesnay, 78157, France

Location

Centre Regional De Lutte Contre Le Cancer

Marseille, 13009, France

Location

Hopital Archet I

Nice, 06202, France

Location

Institut Universitaire du Cancer Toulouse - Oncopole

Toulouse, 31059, France

Location

CHU Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

RWTH Uniklinik Aachen Klinik fur Onkologie, Hamatologie und Stammzelltransplantation

Aachen, 52074, Germany

Location

Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum (CVK)

Berlin, 13353, Germany

Location

Universitaetsklinikum Koeln (AoeR)

Cologne, 50937, Germany

Location

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Klinik fur Innere Medizin II

Jena, 07747, Germany

Location

III. Medizinische Klinik Universitaetsmedizin Mannheim

Mannheim, D-68167, Germany

Location

AOU Policlinico Consorziale di Bari - UO Ematologia con Trapianto

Bari, BA, 70124, Italy

Location

A.O.U. Policlinico S. Orsola-Malpighi

Bologna, BO, 40138, Italy

Location

Azienda Socio Sanitaria Territoriale - ASST Monza

Monza, MB, 20900, Italy

Location

Ospedale S. Eugenio - UOC Ematologia

Rome, RM, 00144, Italy

Location

AOU San Luigi Gonzaga SCDU Medicina Interna II ad indirizzo Ematologico

Orbassano, TO, 10043, Italy

Location

AOU Policlinico Vittorio Emanuele-P.O.G. Rodolico

Catania, 95123, Italy

Location

SOD Ematologia

Florence, 50134, Italy

Location

A.O. Ospedale Niguarda Ca Granda - SC Ematologia

Milan, 20162, Italy

Location

Haukeland Universitetssjukehus

Bergen, 5021, Norway

Location

St Olav Hospital

Trondheim, 7030, Norway

Location

Hospital Universitario Quiron Madrid

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Hospital Universitari Vall d' Hebron

Barcelona, 08035, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic De Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario de La Princesa

Madrid, 28006, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Clinico Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, 46026, Spain

Location

Hospital de dia Quiron Zaragoza

Zaragoza, 50012, Spain

Location

Hematologiskt centrum

Stockholm, 171 76, Sweden

Location

Akademiska Sjukhuset

Uppsala, 751 85, Sweden

Location

Related Publications (5)

• 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.

  PMID: 39164407 DERIVED

• Smith 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.

  PMID: 38484432 DERIVED

• Rosti 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.

  PMID: 38007586 DERIVED

• 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.

  PMID: 35235189 DERIVED

• 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.

  PMID: 32572189 DERIVED

Related Links

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

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia; Bronchiolitis Obliterans Syndrome

Interventions

bosutinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2014
• First Posted: August 29, 2014
• Study Start: November 7, 2014
• Primary Completion: October 13, 2020
• Study Completion: October 13, 2020
• Last Updated: December 30, 2021
• Results First Posted: December 30, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will share

Locations

NO (2); US (13); DE (6); ES (9); FR (6); AU (2); SE (2); IT (8)