Phase 2
N=60
Study of Bosutinib in Japanese Adult Patients With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia
Leukemia, Chronic Myelogenous
Bottom Line
View on ClinicalTrials.gov: NCT03128411 ↗Enrolled (actual)
60
Serious AEs
23.3%
Results posted
Nov 2020
Primary outcome: Primary: Percentage of Participants With Major Molecular Response (MMR) at Month 12 — 55.0 Percentage of participants — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Bosutinib (Drug)
- Age
- Adult, Older Adult · 20+ yrs
- Sex
- All
- Sponsor
- Pfizer
- Primary completion
- Mar 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Major Molecular Response (MMR) at Month 12 |
55.0 | <0.0001 sig |
| SECONDARY Percentage of Participants With Major Molecular Response (MMR) by Month 12 |
61.7 | — |
| SECONDARY Percentage of Participants With Major Molecular Response (MMR) by Month 18 |
66.7 | — |
| SECONDARY Percentage of Participants With Complete Cytogenetic Response (CCyR) by Month 12 |
80.0 | — |
| SECONDARY Probability of Maintaining Major Molecular Response (MMR) at Month 36 |
100.0 | — |
| SECONDARY Probability of Maintaining Complete Cytogenetic Response (CCyR) at Month 36 |
100.0 | — |
| SECONDARY Cumulative Incidence of Event Free Survival (EFS) at Month 36 |
1.7 | — |
| SECONDARY Probability of Overall Survival (OS) at Month 36 |
96.7 | — |
| SECONDARY Trough Plasma Concentrations of Bosutinib |
0.000; 83.564; 85.963; 79.659 | — |
| SECONDARY Summary and Analysis of Trough Bosutinib Plasma Concentration by Major Molecular Response (MMR) Response |
94.943; 59.770; 88.196; 82.092; 81.339; 75.654 | — |
| SECONDARY Summary and Analysis of Trough Bosutinib Plasma Concentration by CCyR Response |
87.006; 28.490; 90.550; 52.936; 79.429; 82.800 | — |
| SECONDARY Summary of Trough Bosutinib Plasma Concentration by Total Bilirubin |
61.833; 96.867; 76.963; 84.599; 60.044; 81.246 | — |
| SECONDARY Summary of Trough Bosutinib Plasma Concentration by Creatinine Clearance |
75.039; 84.114; 100.100; 72.610; 93.056; 92.764 | — |
| SECONDARY Summary of Trough Bosutinib Plasma Concentration by Aspartate Aminotransferase |
65.771; 140.617; 66.056; 82.711; 82.117; 76.050 | — |
| SECONDARY Summary of Trough Bosutinib Plasma Concentration by Alanine Aminotransferase |
49.111; 98.882; 94.175; 86.000; 66.878; 82.317 | — |
| SECONDARY Summary and Analysis of Trough Bosutinib Plasma Levels by Presence/Absence Grade 1: Diarrhea |
85.585; 74.133; 86.086; 85.080; 85.219; 50.271 | — |
| SECONDARY Summary and Analysis of Trough Bosutinib Plasma Levels by Presence/Absence Grade 1: Nausea |
90.998; 81.971; 111.482; 76.606; 91.867; 76.520 | — |
| SECONDARY Summary and Analysis of Trough Bosutinib Plasma Levels by Presence/Absence Grade 1: Vomiting |
58.826; 89.977; 87.135; 85.533; 90.030; 76.609 | — |
| SECONDARY Summary and Analysis of Trough Bosutinib Plasma Levels by Presence/Absence Grade 1: Thrombocytopenia |
80.167; 83.893; 87.700; 85.722; 75.067; 79.995 | — |
| SECONDARY 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 |
49 | — |
| SECONDARY Number of Participants With Laboratory Abnormalities, Chemistry: National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 or 4 |
30; 1; 16; 1; 3; 2 | — |
| SECONDARY Number of Participants With Laboratory Abnormalities, Hematology: National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 or 4 |
4; 14; 9; 6; 2 | — |
| SECONDARY Number of Participants With Laboratory Abnormalities, Coagulation: National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.03) Grade 3 |
0; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Vital Signs Findings |
12; 2; 0; 0; 1; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings |
0; 0; 1 | — |
| SECONDARY Number of Participants Assessed for Left Ventricular Ejection Fraction |
15; 3; 0 | — |
| SECONDARY Percentage of Participants With Major Molecular Response (MMR) at Months 3, 6, 9 and 18 |
10.0; 50.0; 53.3; 61.7 | — |
| SECONDARY Percentage of Participants With Molecular Response 1 (MR1) at Month 3 |
80.0 | — |
| SECONDARY Percentage of Participants With Molecular Response 2 (MR2) at Month 6 |
66.7 | — |
| SECONDARY Percentage of Participants With Molecular Response 4.0 (MR4.0) and Molecular Response 4.5 (MR4.5) at Months 3, 6, 9 and 12 |
0; 18.3; 25.0; 31.7; 0; 8.3 | — |
| SECONDARY Cumulative Incidence of Major Molecular Response (MMR) at Month 36 |
70.0 | — |
| SECONDARY Cumulative Incidence of Molecular Response 4.0 (MR4.0) at Month 36 |
50.0 | — |
| SECONDARY Cumulative Incidence of Molecular Response 4.5 (MR4.5) at Month 36 |
46.7 | — |
| SECONDARY Cumulative Incidence of Complete Cytogenetic Response (CCyR) at Month 36 |
80.0 | — |
| SECONDARY Percentage of Participants With Cumulative Complete Haematological Response (CHR) |
91.7 | — |
| SECONDARY Cumulative Incidence of Transformation to Accelerated Phase (AP) and Blast Phase (BP) at Month 36 |
NA | — |
| SECONDARY Number of Participants With BCR-ABL Mutation at Treatment Discontinuation |
— | — |
Summary
Phase 2, single-arm, open-label trial. Patients will receive bosutinib for the duration of the study.
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
Data sourced from ClinicalTrials.gov (NCT03128411). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.