Safety and Efficacy Study of Bosutinib in Patients With Philadelphia Chromosome Positive Chronic Myeloid Leukemia Previously Treated with one or two more Tyrosine Kinase Inhibitors

Phase 1

• Conditions: Philadelphia Chromosome Positive Chronic Myeloid Leukaemia; MedDRA version: 20.0Level: PTClassification code 10009013Term: Chronic myeloid leukaemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-003250-25-FI
• Lead Sponsor: Pfizer Inc, 235 East 42nd Street, New York, NY 10017

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-05-22
• Last Update Posted: 28 August 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 165

Inclusion Criteria

1. Cytogenetic or PCR-based diagnosis of Ph+ CML or BCR-ABL1+ if Ph- (from initial diagnosis). NOTE: Ph- subjects will not count towards the 150 patients for primary and secondary analyses, which include Ph+ patients only.
2. Prior treatment with 1 or more TKIs for CML.
3. Any CML phase, as long as the patient is resistant to, intolerant of, or otherwise not appropriate for treatment with imatinib, dasatinib and/or nilotinib.
4. ECOG Performance Status of 0 or 1 for CP patients, or 0, 1, 2, or 3 for 4th line CP (and beyond) and AP/ BP patients.
5. Adequate bone marrow function:
For 2nd and 3rd line CP CML patients:
(1) Absolute neutrophil count >1000/mm3 (>1 x109/L).
(2) Platelets =75,000/mm3 (=75 x109/L) absent any platelet transfusions during the preceding 14 days.
For 4th line CP and AP/BP CML patients:
(1) Absolute neutrophil count >500/mm3 (>0.5 x109/L).
(2) Platelets =50,000/mm3 (=50 x109/L) absent any platelet transfusions during the preceding 14 days.
6. Adequate hepatic and renal function:
(a) AST/ALT =2.5 x ULN or ALT/AST =5 x ULN if attributable to liver involvement of leukaemia.
(b) Total direct bilirubin =1.5 x ULN.
(c) Creatinine =1.5 x ULN.
7. Able to take daily oral tablets.
8. Age =18 years.
9. Evidence of a personally signed and dated informed consent document indicating that the patient (or a legal representative) has been informed of all pertinent aspects of the study.
10. Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
11. Male and female patients of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 28 days after the last dose of assigned treatment. A patient is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 132
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 33

Exclusion Criteria

1. Participation in other studies involving investigational drug(s) (Phase 1-4) within 14
days or 3 half-lives (whichever is longer) prior to the first dose of bosutinib.
2. Prior bosutinib exposure.
3. Prior ponatinib exposure.
4. Known T315I or V299L mutation in BCR-ABL1.
5. Clinically active leptomeningeal leukemia. Patients must be free of central nervous system (CNS) involvement for a minimum of 2 months.
6. Hypersensitivity to the active substance or to any of the following excipients:
Microcrystalline cellulose (E460), Croscarmellose sodium (E468), Poloxamer 188, Povidone (E1201), Magnesium stearate (E470b), Polyvinyl alcohol, Titanium dioxide (E171), Macrogol 3350, Talc (E553b), Iron oxide red (E172).
7. Pregnant or breastfeeding females.
8. Males and females of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after last dose of investigational product.
9. Other severe acute or chronic medical or psychiatric condition, including recent (within the past year) or active suicidal ideation or behavior) or laboratory
abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
10. Patients who are investigational site staff members directly involved in the conduct of the trial and their family members, site staff members otherwise supervised by the Investigator, or patients who are Pfizer employees directly involved in the conduct of the trial.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified