Patients with chromosome Philadelphia positive (Ph+) in chronic phase mielogenus leukemia (CP CML) MedDRA version: 18.0 Level: PT Classification code 10034877 Term: Philadelphia chromosome positive System Organ Class: 10022891 - Investigations
Conditions
Interventions
Product Name: Bosutinib
Pharmaceutical Form: Coated tablet
INN or Proposed INN: BOSUTINIB
CAS Number: 380843-75-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10
Sponsors
Fundación PETHEMA para el tratamiento de la leucemia y el linfoma
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Signed and dated informed consent form. 2.Patients with chronic phase of Ph+ CML who showed failure to previous TKI treatment. Failure is defined as BCR-ABL >10% by qRT-PCR (IS) at 3 months of treatment initiation. 3.ECOG Performance Status of 0 or 1. 4.Recovered to Grade 0-1, or to baseline, from any toxicities of prior treatment, other than alopecia 5.Able to take daily oral capsules 6.Adequate bone marrow function: a. Absolute neutrophil count > 1000/mm3 (>1000 x109/L) b. Platelets ? 100,000/mm3 (>100 x109/L) absent any platelet transfusions during the preceding 14 days. 7.Adequate hepatic, and renal function: oAST/ALT ? 2.5 × upper limit of normal (ULN) or ? 5 × ULN if attributable to liver involvement of leukemia oTotal bilirubin ? 1.5 × ULN oCreatinine ? 1.5 × ULN 8.Age > 18 years 9.Willingness of male and female subjects, who are not surgically sterile or postmenopausal, to use reliable methods of birth control (oral contraceptives, intrauterine devices, or barrier methods used with a spermicide) for the duration of the study and for 30 days after the last dose of Bosutinib. 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 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: 1.Subjects with Philadelphia chromosome and bcr-abl negative CML. 2. Overt leptomeningeal leukemia. Subjects must be free of CNS involvement for a minimum of 2 months. Subjects with symptoms of CNS involvement must have a diagnostic lumbar puncture prior to study enrollment. 3.Subjects with extramedullary disease only. 4.Prior stem cell transplantation. 5.Major surgery within 14 days or radiotherapy within 7 days before the first dose of Bosutinib (recovery from any previous surgery should be complete before day 1) 6.A history of a clinically significant ventricular arrhythmia, congenital or acquired prolonged QT interval, a baseline QTcF > 0.47 sec (average of triplicate readings) or unexplained syncope, uncontrolled or symptomatic congestive heart failure (CHF) within 3 months, or myocardial infarction (MI) within 6 months. 7.Concomitant use of or need for medications known to prolong the QT interval 8.Uncorrected hypomagnesemia or hypokalemia due to potential effects on the QT interval 9.Recent (within 30 days of study entry) or ongoing clinically significant gastrointestinal disorder (e.g., malabsorption, short bowel syndrome, bleeding, or grade >1 diarrhea, nausea or emesis lasting more than 2 days, despite adequate medical therapy) 10.Pregnant or breastfeeding women 11.Evidence of serious active infection, or significant medical or psychiatric illness 12.Known seropositivity to HIV, or current acute or chronic Hepatitis B or Hepatitis C (antigen positive), cirrhosis, hypokalemia (any grade), or clinically significant abnormal laboratory finding that would, in the investigator?s judgment, make the subject inappropriate for this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Assess single nucleotide polymorphisms in genes potentially relevant for bosutinib action, metabolism and transport and if there is an association between this and the drug activity and toxicity.;Secondary Objective: - Assess the eficacy and toxicity of bosutinib in patients after relapse or intolerance to previous tyrosine kinase inhibitors . - Assess the bosutinib eficacy reason depending on the failure of the previous treatment.;Primary end point(s): Assess single nucleotide polymorphisms in genes potentially relevant for bosutinib action, metabolism and transport and if there is an association between this and the drug activity and toxicity.;Timepoint(s) of evaluation of this end point: End of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Assess the eficacy and toxicity of bosutinib in patients after relapse or intolerance to previous tyrosine kinase inhibitors . - Assess the bosutinib eficacy reason depending on the failure of the previous treatment.;Timepoint(s) of evaluation of this end point: End of treatment | — |
Countries
Spain
Contacts
Public ContactDr. Alfonso J. Santiago Marí
Fundación Pethema
Outcome results
None listed