Clinical trial NCT03128411: Study of Bosutinib in Japanese Adult Patients With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia
Official title: A PHASE 2, OPEN-LABEL, SINGLE-ARM STUDY TO EVALUATE EFFICACY AND SAFETY OF BOSUTINIB MONOTHERAPY IN JAPANESE ADULT PATIENTS WITH NEWLY DIAGNOSED CHRONIC PHASE CHRONIC MYELOGENOUS LEUKEMIA
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia, Chronic Myelogenous
Keywords: Leukemia, Chronic Myelogenous
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2017-04-25
Enrollment: 64
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Phase 2, single-arm, open-label trial. Patients will receive bosutinib for the duration of the study.

Detailed description: The study will be open for enrollment until the planned number of approximately 60 Philadelphia Chromosome Positive (Ph+) patients have been registered. All patients will be treated and/or followed for up to approximately 3 years (144 weeks) after registration of the last patient or until study termination. Patients who discontinue study therapy early due to disease progression or intolerance to study medication will continue to be followed yearly for survival for up to approximately 3 years (144 weeks) after registration of the last patient or until study termination.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of CP CML of ≤6 months (from initial diagnosis); Diagnosis of CP CML with molecular confirmation by detection of BCR-ABL rearrangement at screening (cytogenetic assessment for Ph is not required for enrollment; however, patients with known Ph- CML prior to registration are not eligible for this study)
* Age ≥20 years
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
* Adequate Liver and Renal Function

Exclusion Criteria:

* Any prior medical treatment for CML, including TKIs, with the exception of hydroxyurea treatment, which is permitted for up to 6 months prior to registration
* Any past or current CNS involvement, including leptomeningeal leukemia
* Extramedullary disease only
* Major surgery or radiotherapy within 14 days prior to registration
* History of clinically significant or uncontrolled cardiac disease
* Patients with active, uncontrolled bacterial, fungal, or viral infection
* Recent or ongoing clinically significant GI disorder
* History of another malignancy within 5 years prior to registration
* Uncontrolled hypomagnesemia or uncorrected hypokalemia due to potential effects on the QT interval
* Known prior or suspected severe hypersensitivity to study drugs or any component in their formulations
* Participation in other studies involving investigational drug(s) within 30 days or 5 half-lives of investigational product, whichever is longer, prior to registration and/or during study participation
* Other severe acute or chronic medical or psychiatric condition, including recent or active suicidal ideation or behavior, or laboratory abnormality that may increase the risk associated with study participation or interfere with the interpretation of study results
* Investigational site staff members directly involved in the conduct of the study and their family members, or Pfizer employees, including their family members, directly involved in the conduct of the study

Primary outcomes:
measure: Percentage of Participants With Major Molecular Response (MMR) at Month 12
timeFrame: Month 12
Secondary outcomes:
measure: Percentage of Participants With Major Molecular Response (MMR) by Month 12
timeFrame: Up to Month 12
measure: Percentage of Participants With Major Molecular Response (MMR) by Month 18
timeFrame: Up to Month 18
measure: Percentage of Participants With Complete Cytogenetic Response (CCyR) by Month 12
timeFrame: Up to Month 12
measure: Probability of Maintaining Major Molecular Response (MMR) at Month 36
timeFrame: At Month 36
measure: Probability of Maintaining Complete Cytogenetic Response (CCyR) at Month 36
timeFrame: At Month 36
measure: Cumulative Incidence of Event Free Survival (EFS) at Month 36
timeFrame: Up to Month 36
measure: Probability of Overall Survival (OS) at Month 36
timeFrame: Up to Month 36
measure: Trough Plasma Concentrations of Bosutinib
timeFrame: Pre-dose on Day 1, Day 28, Day 56, Day 84
measure: Summary and Analysis of Trough Bosutinib Plasma Concentration by Major Molecular Response (MMR) Response
timeFrame: Pre-dose on Day 28, Day 56 and Day 84
measure: Summary and Analysis of Trough Bosutinib Plasma Concentration by CCyR Response
timeFrame: Pre-dose on Day 28, Day 56 and Day 84
measure: Summary of Trough Bosutinib Plasma Concentration by Total Bilirubin
timeFrame: Pre-dose on Day 28, Day 56 and Day 84
measure: Summary of Trough Bosutinib Plasma Concentration by Creatinine Clearance
timeFrame: Pre-dose on Day 28, Day 56 and Day 84
measure: Summary of Trough Bosutinib Plasma Concentration by Aspartate Aminotransferase
timeFrame: Pre-dose on Day 28, Day 56 and Day 84
measure: Summary of Trough Bosutinib Plasma Concentration by Alanine Aminotransferase
timeFrame: Pre-dose on Day 28, Day 56 and Day 84
measure: Summary and Analysis of Trough Bosutinib Plasma Levels by Presence/Absence Grade 1: Diarrhea
timeFrame: Pre-dose on Day 28, Day 56 and Day 84 for trough bosutinib plasma concentration up to 12 March 2019; maximum of 22 months, approximately, for the adverse event of interest
measure: Summary and Analysis of Trough Bosutinib Plasma Levels by Presence/Absence Grade 1: Nausea
timeFrame: Pre-dose on Day 28, Day 56 and Day 84 for trough bosutinib plasma concentration up to 12 March 2019; maximum of 22 months, approximately, for the adverse event of interest
measure: Summary and Analysis of Trough Bosutinib Plasma Levels by Presence/Absence Grade 1: Vomiting
timeFrame: Pre-dose on Day 28, Day 56 and Day 84 for trough bosutinib plasma concentration up to 12 March 2019; maximum of 22 months, approximately, for the adverse event of interest
measure: Summary and Analysis of Trough Bosutinib Plasma Levels by Presence/Absence Grade 1: Thrombocytopenia
timeFrame: Pre-dose on Day 28, Day 56 and Day 84 for trough bosutinib plasma concentration up to 12 March 2019; maximum of 22 months, approximately, for the adverse event of interest
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs): National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 or Higher
timeFrame: From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months)
measure: Number of Participants With Laboratory Abnormalities, Chemistry: National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 or 4
timeFrame: From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months)
measure: Number of Participants With Laboratory Abnormalities, Hematology: National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 or 4
timeFrame: From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months)
measure: Number of Participants With Laboratory Abnormalities, Coagulation: National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3
timeFrame: From first dose and up to 12 March 2019; maximum of 22 months, approximately
measure: Number of Participants With Clinically Significant Vital Signs Findings
timeFrame: From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months)
measure: Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings
timeFrame: From first dose and up to 28 days after the last dose of study drug (maximum up to 45 months)
measure: Number of Participants Assessed for Left Ventricular Ejection Fraction
timeFrame: At end of treatment for patients who discontinued treatment post initial dose (up to 12 March 2019)
measure: Percentage of Participants With Major Molecular Response (MMR) at Months 3, 6, 9 and 18
timeFrame: Month 3, 6, 9 and 18
measure: Percentage of Participants With Molecular Response 1 (MR1) at Month 3
timeFrame: Month 3
measure: Percentage of Participants With Molecular Response 2 (MR2) at Month 6
timeFrame: Month 6
measure: Percentage of Participants With Molecular Response 4.0 (MR4.0) and Molecular Response 4.5 (MR4.5) at Months 3, 6, 9 and 12
timeFrame: Months 3, 6, 9 and 12
measure: Cumulative Incidence of Major Molecular Response (MMR) at Month 36
timeFrame: At Month 36
measure: Cumulative Incidence of Molecular Response 4.0 (MR4.0) at Month 36
timeFrame: At Month 36
measure: Cumulative Incidence of Molecular Response 4.5 (MR4.5) at Month 36
timeFrame: At Month 36
measure: Cumulative Incidence of Complete Cytogenetic Response (CCyR) at Month 36
timeFrame: At Month 36
measure: Percentage of Participants With Cumulative Complete Haematological Response (CHR)
timeFrame: Up to Month 36
measure: Cumulative Incidence of Transformation to Accelerated Phase (AP) and Blast Phase (BP) at Month 36
timeFrame: At Month 36
measure: Number of Participants With BCR-ABL Mutation at Treatment Discontinuation
timeFrame: Maximum up to 44 months of treatment
Other outcomes:
Locations:
city: Toyoake-City
country: Japan
facility: Fujita Health University Hospital
state: Aichi
city: Toyohashi
country: Japan
facility: Toyohashi Municipal Hospital
state: Aichi
city: Akita City
country: Japan
facility: Akita University Hospital
state: Akita
city: Narita
country: Japan
facility: Japanese Red Cross Narita Hospital
state: Chiba
city: Toon-shi
country: Japan
facility: Ehime University Hospital
state: Ehime
city: Kobe-city
country: Japan
facility: Kobe City Medical Center General Hospital
state: Hyogo
city: Kanazawa
country: Japan
facility: Ishikawa Prefectural Central Hospital
state: Ishikawa
city: Yokohama
country: Japan
facility: Yokohama City University Medical Center
state: Kanagawa
city: Kawachinagano
country: Japan
facility: National Hospital Organization Osaka Minami Medical Center
state: Osaka
city: Osaka-City
country: Japan
facility: Osaka City University Hospital
state: Osaka
city: Osaka-Sayama
country: Japan
facility: Kindai University Hospital
state: Osaka
city: Hamamatsu
country: Japan
facility: Hamamatsu University Hospital
state: Shizuoka
city: Bunkyo-ku
country: Japan
facility: Juntendo University Hospital
state: Tokyo
city: Bunkyo-ku
country: Japan
facility: Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital
state: Tokyo
city: Shinagawa-ku
country: Japan
facility: NTT Medical Center Tokyo
state: Tokyo
city: Tachikawa
country: Japan
facility: National Hospital Organization Disaster Medical Center
state: Tokyo
city: Yamagata-Shi
country: Japan
facility: Yamagata University Hospital
state: Yamagata
city: Chiba
country: Japan
facility: Chiba University Hospital
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Saga
country: Japan
facility: Saga University Hospital
city: Tokyo
country: Japan
facility: Nippon Medical School Hospital
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Ono T, Hino M, Matsumura I, Fujisawa S, Ishizawa K, Sakaida E, Sekiguchi N, Ono C, Aizawa M, Tanetsugu Y, Koide Y, Takahashi N. Bosutinib in Japanese patients with newly diagnosed chronic-phase chronic myeloid leukemia: final 3-year follow-up results of a phase 2 study. Int J Hematol. 2022 Dec;116(6):871-882. doi: 10.1007/s12185-022-03435-4. Epub 2022 Aug 13.
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: Hino M, Matsumura I, Fujisawa S, Ishizawa K, Ono T, Sakaida E, Sekiguchi N, Tanetsugu Y, Fukuhara K, Ohkura M, Koide Y, Takahashi N. Phase 2 study of bosutinib in Japanese patients with newly diagnosed chronic phase chronic myeloid leukemia. Int J Hematol. 2020 Jul;112(1):24-32. doi: 10.1007/s12185-020-02878-x. Epub 2020 Apr 11.