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
- Conditions
- Philadelphia Chromosome Positive Chronic Myeloid LeukaemiaMedDRA version: 21.1Level: 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-SE
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 165
1. Cytogenetic or PCR-based diagnosis of Ph+ CML or BCR-ABL1+ if Ph- (from initial diagnosis). NOTE: Ph-CML patients will not count towards the 150 patients for primary and secondary analyses, which include Ph+ CML patients only.
NOTE: All patients must have screening bone marrow (BM) cytogenetic analysis with conventional G banding performed within 30 days prior to study entry (unless CML disease status is proven to be MMR by quantitative reverse transcription polymerase chain reaction [qRT-PCR]). Examination of at least 20 metaphases is required.
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:
• Absolute neutrophil count >1000/mm3 (>1 x109/L).
• 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:
• Absolute neutrophil count >500/mm3 (>0.5 x109/L).
• Platelets =50,000/mm3 (=50 x109/L) absent any platelet transfusions during the preceding 14 days.
6. Adequate hepatic and renal function:
• AST/ALT =2.5 x the upper limit of normal ULN or ALT/AST =5 x ULN if attributable to liver involvement of leukemia.
• Total bilirubin =1.5 x ULN (unless the bilirubin is principally unconjugated and there is a strong suspicion of subclinical hemolysis (e.g. chronic hemolysis without clinical symptoms), or the patient has documented Gilbert's Disease);
• Alkaline phosphatase =2.5 x ULN.
• Creatinine =1.5 x ULN or estimated creatinine clearance (CrCL) =60 mL/min as calculated using the standard method for the institution.
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 legally acceptable representative/legal guardian) 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 two highly effective methods 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
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 or ponatinib exposure.
3. Prior hydroxyurea or anagrelide exposure within 72 hours of the baseline CML disease assessment.
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 two highly effective methods 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
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method