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

• ClinicalTrials.gov Identifier: NCT02228382
• Recruitment Status: Active, not recruiting
• First Posted: August 29, 2014
• Last Update Posted: March 7, 2019
• Sponsor: Pfizer
• Collaborator: Developmental Therapeutics Consortium
• Information provided by (Responsible Party): Pfizer

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Previously Treated PH + CML	Drug: Bosutinib	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 163 participants
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: November 7, 2014
• Estimated Primary Completion Date: September 18, 2021
• Estimated Study Completion Date: September 18, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Bosutinib	Drug: Bosutinib; 100 mg and 500 mg tablets, once daily dosage up to 4 years duration; Other Name: BOSULIF

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants with Major Cytogenetic Response (MCyR) by Week 52 in Chronic Phase Second-line Population and Chronic Phase Third-line Population of Philadelphia Chromosome Positive Chronic Myeloid Leukemia patients. [ Time Frame: Week 52 ]
   Cytogenetic response (CyR) is based on the prevalence of Philadelphia positive cells in metaphase from Bone Marrow sample.
2. Percentage of Participants with Major Cytogenetic Response (MCyR) by Week 52 in Chronic Phase Fourth-line and later-line Population of Philadelphia Chromosome Positive Chronic Myeloid Leukemia patients. [ Time Frame: Week 52 ]
   Cytogenetic response (CyR) is based on the prevalence of Philadelphia positive cells in metaphase from Bone Marrow sample.
3. Percentage of Participants with Overall Hematologic Response (OHR) by Week 52 in Advanced Leukemia Population patients. [ Time Frame: Week 52 ]
   OHR includes Complete Hematological Response (CHR) or return to chronic phase (RCP).

Secondary Outcome Measures :

1. Estimate cumulative probability of Percentage of Participants with Major Cytogenetic Response in Chronic Phase and Advanced Phase Philadelphia Chromosome Positive Chronic Myeloid Leukemia patient populations. [ Time Frame: Week 52 ]
   Cytogenetic response (CyR) is based on the prevalence of Philadelphia positive cells in metaphase from Bone Marrow sample.
2. Estimate cumulative probability of Percentage of Participants with Overall Hematologic Response in the Accelerated Phase and Blast Phase Philadelphia Chromosome Positive Chronic Myeloid Leukemia patient population by number of lines of prior therapy. [ Time Frame: Week 52 ]
   OHR includes Complete Hematological Response (CHR) or return to chronic phase (RCP).
3. Characterize distribution of best response (molecular, cytogenetic, or hematologic) in the Chronic Phase, Accelerated Phase and Blast Phase Philadelphia Chromosome Positive Chronic Myeloid Leukemia patient populations. [ Time Frame: Week 52 ]
4. Estimating probability of Percentage of Participants with Major Cytogenetic Response at 3, 6, 12, 18, and 24 months in the Chronic Phase, Accelerated Phase and Blast Phase Philadelphia Chromosome Positive Chronic Myeloid Leukemia patient populations. [ Time Frame: Month 3, 6, 12, 18, and 24 ]
5. Estimating the probability of confirmed Overall Hematologic Response at 3, 6, 9, 12, 18, and 24 months in the Accelerated Phase and Blast Phase Philadelphia Chromosome Positive Chronic Myeloid Leukemia patient populations. [ Time Frame: Month 3, 6, 9, 12, 18, and 24 ]
6. Estimating the probability of cumulative confirmed Complete Hematologic Response in the Chronic Phase, Accelerated Phase and Blast Phase Philadelphia Chromosome Positive Chronic Myeloid Leukemia patient populations. [ Time Frame: Week 52 ]
7. Estimating the probability of cumulative major molecular response in the Chronic Phase, Accelerated Phase and Blast Phase Philadelphia Chromosome Positive Chronic Myeloid Leukemia patient populations. [ Time Frame: Week 52 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

  Show 49 Study Locations

Sponsors and Collaborators

Pfizer

Developmental Therapeutics Consortium

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

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

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT02228382 History of Changes
• Other Study ID Numbers: B1871039; 2013-003250-25 ( EudraCT Number ); BYOND ( Other Identifier: Alias Study Number )
• First Posted: August 29, 2014
• Last Update Posted: March 7, 2019
• Last Verified: March 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: 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.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

Keywords provided by Pfizer:

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

Additional relevant MeSH terms:

Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Philadelphia Chromosome; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Translocation, Genetic; Chromosome Aberrations; Pathologic Processes