Study design and pts
death, CML, diarrhea, CP-CML, toxicities, toxicity, GI toxicity, leptomeningeal leukemia
DISEASE PROGRESSION, RECRUITMENT, CML, ADVERSE EVENT, ONCOLOGY
The BODO trial (NCT02577926; CML-7 Study) is a multicenter, open label, single-arm, non-randomized phase II trial testing the tolerability and efficacy of 2nd and 3rd line bosutinib step-in dosing in CP CML pts intolerant and/or refractory to previous TKI therapy. Eligible pts were adults with a cytogenetic or qualitative polymerase chain reaction (PCR)–based diagnosis of Ph + and/or BCR::ABL1 + CP-CML, prior treatment with one or maximum two lines of TKI treatment for CML, and adequate hepatic/renal function (for details, please find attached the study protocol in the supplement of this article). An initial pre-treatment with imatinib for up to 6 weeks did not count as an autonomous line of therapy. Pts were required to have Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1; pts with leptomeningeal leukemia or a known BCR::ABL1 T315I or V299L mutation were excluded. Intolerance to prior therapy was 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 persisted ≥ 1 month or recurred > 2 times with TKI dose reduction or which was medically significant (independent of grade) and according to investigator’s opinion lead to change of TKI. Resistance to prior therapy was defined as not achieving optimal response to Imatinib OR Nilotinib OR Dasatinib according to ELN2013-defined recommendations [Bosutinib was commenced with 300 mg QD and was (in the absence of > G 1 toxicities) dose-increased by increments of 100 mg daily dosing every 14 days up to a maximum target dose of 500 mg QD. Consecutive dose reductions to 400, 300, or 200 mg QD due to toxicity/tolerability were permitted. Special recommendations regarding management of bosutinib-related diarrhea were given to physicians and patients and early use of prophylactic medication such as loperamide after onset of diarrhea was encouraged. Planned observation was 2 years from the time of first dose, unless disease progression, unacceptable toxicity, withdrawal of consent, death, or study discontinuation.Initially recruitment of 127 subjects who would have received at least 14 daily doses of study medication was planned to ensure sufficient power for a reasonable assessment of grade 2–4 GI toxicity as the primary endpoint. Sample size calculation and determination of the exact CI were based on Chow and colleagues [