Chronic Phase Chronic myelogenous leukaemia( CP-CML) patients who either developed intolerance or treatment failure to previous Imatinib, Dasatinib or Nilotinib as 1st or 2nd line therapy.
Conditions
Interventions
Trade Name: Bosulif
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Bosutinib
Current Sponsor code: MED3-201401-BODO
Concentration unit: mg milligram(s)
Concentration number: 100-
Trade
Sponsors
Univerity of Bonn
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed written informed consent 2. Male or female patients aged =18 years 3. ECOG performance status of 0 to 2 4. CML in 1st or late chronic phase 5. Intolerant* or resistant** to pretreatment with one or two of the approved first line TKI (Imatinib, Nilotinib or Dasatinib). Imatinib therapy prior to 2nd generation TKI therapy for a maximum of 6 weeks is allowed. 6. Patients must have a serum creatinine of = 2 x ULN, SGOT/SGPT = 3 x ULN, total bilirubin = 2 x ULN (except known Gilbert’s syndrome), and Lipase = 1.5 x ULN 7. Female patients of childbearing potential must have a negative pregnancy test performed during screening period 8. Male and female patients of reproductive potential must agree to employ a highly effective contraceptive method*** throughout the study and for 6 months following discontinuation of study drug. * Intolerance is defined as discontinuation of Imatinib OR Nilotinib OR Dasatinib due to grade 3 or 4-related adverse event (AE), despite optimal supportive care, or because of a persistent grade 2-related AE, despite optimal supportive care, which persists =1 month or recurs >2 times with TKI dose reduction or which is medically significant (independent of grade) and according to investigator´s opinion should lead to change of TKI. ** Resistance is defined as not achieving optimal response to Imatinib OR Nilotinib OR Dasatinib according to ELN2013-defined recommendations (Baccarani, Blood 2013). Optimal response is defined as: - BCR-ABL1 = 10% and/or Ph+ = 35% at 3 months - BCR-ABL1 =65 years) yes F.1.3.1 Number of subjects for this age range 63
Exclusion criteria
Exclusion criteria: 1. Hypersensitivity against Bosutinib or other ingredients of the medicinal product 2. Evidence of features of accelerated (AP) or blast phase (BC) at any time before inclusion 3. Patients with BCR-ABL negative CML 4. Patients having received Imatinib for more than 6 weeks prior to initiation of 2nd generation TKI (either Nilotinib or Dasatinib) 5. Patients with known T315I or V299L mutation 6. Concomitant medications known to be strong inducers or inhibitors of P450 isoenzyme CYP3A4 (see www.drug-interactions.com) 7. History of pancreatitis, inflammatory bowel disease requiring systemic or topical immunosuppressive therapy within the last 12 months 8. Impaired cardiac function, including any of the following: a. History of or presence of complete left bundle branch block, right bundle branch block plus left anterior hemiblock, bifascicular block in screening ECG b. ST depression of >1mm in 2 or more leads and/or T wave inversions in 2 or more contiguous leads in screening ECG c. Congenital long QT syndrome d. QTc> 450 msec in the screening ECG e. QT-prolonging concomitant medication f. History of or presence of significant ventricular or atrial tachyarrhythmias in screening ECG g. History of or presence of clinically significant resting bradycardia (< 50 beats per minute) h. Myocardial infarction within 6 months prior to inclusion i. Unstable angina diagnosed or treated during the past 12 months j. Uncontrolled hypertension, history of labile hypertension 9. Known HIV and/or active viral hepatitis (hepatitis B or C). Hepatitis B screening will be performed at screening. Patients with a history of hepatitis B with negative HBV DNA may be included when using antiviral prophylaxis. 10. Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinoma of the skin 11. Treatment with another investigational product during this study or during the last 30 days prior to study start except treatment with interferon-alpha within the TIGER (CML V) protocol, which must be stopped at least 7 days prior to study start 12. Any circumstance at the time of study entry that would preclude completion of the study or the required follow-up prohibits inclusion into this study 13. Patient must not have any active bacterial, viral or fungal infection at screening 14. Patient must not have severe cerebral dysfunction and/or legal incapacity 15. Conditions which interfere with the study treatment at the discretion of the investigator 16. Women who are pregnant or breast feeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of the BODO trial is to assess the tolerability and efficacy of a step-in dosing concept of the dual SRC-ABL kinase inhibitor Bosutinib in CP-CML patients who either developed intolerance or treatment failure to previous Imatinib, Dasatinib or Nilotinib as 1st or 2nd line therapy ;Secondary Objective: To assess: • Tolerability (i.e. all grade, grade 2 to 4 and grade 3 and 4 toxicities) at month 6, 12 and 24 • Efficacy parameters: MMR (Major Molecular Response), MR4 (Molecular Response with a sensitivity of 1:10000), MR4.5 (Molecular Response with a sensitivity of 1:50000) and CCyR (Complete Cytogenetic Response) rate at month 3, 6, 12, 18 and 24 • Patient-reported outcome measures (QoL) • Progression-free survival (PFS) • Overall survival (OS) • The rate of emerging mutations during Bosutinib treatment ;Primary end point(s): Rate of GI-Toxicity (i.e. incidence and severity of grade 2 to 4 toxicities) within the first 6 months of treatment;Timepoint(s) of evaluation of this end point: at Screening (visit 1), first application of IMP = Day 1 (visit 2), during dose escalation every 14 days until end of month 3 (visit 3 to 7), end of month 3 (visit 8) and end of month 6 (visit 9) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Tolerability (i.e. all grade, grade 2 to 4 as well as grade 3 and 4 toxicities) • Efficacy parameters: MMR (Major Molecular Response), MR4 (Molecular Response with a sensitivity of 1:10000), MR4.5 (Molecular Response with a sensitivity of 1:50000) and CCyR (Complete Cytogenetic Response) rate • Patient-reported outcome measures (QoL) • Progression-free survival (PFS) • Overall survival (OS) • The rate of emerging mutations during Bosutinib treatment ;Timepoint(s) of evaluation of this end point: • Tolerability (i.e. all grade, grade 2 to 4 as well as grade 3 and 4 toxicities) at 6, 12 and 24 months (visit 9, 11 and 15) • Efficacy parameters: MMR, MR4, MR4.5 and CCyR rate at month 3, 6, 12, 18 and 24 (visit 8, 9, 11, 13 and 15) • Patient-reported outcome measures (QoL) at Screening (visit 1), first application of IMP = Day 1 (visit 2), during dose escalation every 14 days until end of month 3 (visit 3 to 7), every 3 month until end of study (visit 8 to 15) • Progression-free survival (PFS), Overall survival (OS) and the rate of emerging mutations during Bosutinib treatment during dose escalation every 14 days until end of month 3 (visit 3 to 7), every 3 month until end of study (visit 8 to 15) | — |
Countries
Germany
Contacts
Public ContactDr. Mareille Warnken-Uhlich
Studienzentrale Studienzentrum Bonn (SZB)
Outcome results
None listed