An open-label phase II dose optimization study of bosutinib at a starting dose of 400 mg daily for adult patients with chronic myeloid leukemia (CML) in chronic phase post frontline TKI failure
Philip A. Thompson
Bosutinib is a type of tyrosine kinase inhibitor (TKI) which is commonly used for the treatment of chronic phase chronic myelogenous leukemia (CP CML). The standard dose of bosutinib often causes temporary, but severe, diarrhea which goes away after bosutinib is stopped or the dose is lowered. The goal of this clinical research study it to learn if a lower dose of bosutinib is as effective as the standard dose. Researchers think that by starting with a lower dose of bosutinib and slowly increasing the dose (if needed), the likelihood and severity of diarrhea and other side effects may be lowered in patients with CP CML. To help researchers learn if the lower dose of bosutinib is as effective as the regular dose, researchers will test your cytogenetic response to the drug. Cytogenetic testing looks at how genetic changes to cells (in this study, the BRC-ABL protein and Philadelphia chromosome) may affect how the disease may react to the study drug.
Treatment Location: N/A
Primary: To assess the response rate within 24 weeks in patients in chronic phase receiving an escalating schedule of bosutinib with the starting dose of 400 mg per day, with potential escalation to 500 mg and subsequently 600mg per day. Response is defined as follows: 1. For patients who do not currently have a partial cytogenetic response (PCyR), achievement of major cytogenetic response (MCyR) is considered a response. 2. For patients who are currently in PCyR, achievement of complete cytogenetic response (CCyR), CCyR is considered a response. Secondary: · Safety of dosing schedule. · Frequency of treatment interruptions and dose reductions. · Determine the rate of BCR-ABL/ABL <10% at 3 months and <1% at 6 months on the international scale and the rate of complete cytogenetic response (CCyR) at 6 months after the start of treatment. · Determine the cumulative rate of CCyR. · Determine the rate of major molecular response, MR4, MR4.5 and complete molecular response. · Determine long-term outcomes, including progression-free survival, event-free survival, and overall survival. · Investigate the correlation between ABL kinase domain mutations, if present at the time of enrollment, with outcome. · Determine the rate of development and type of ABL kinase domain mutations during therapy with bosutinib. Exploratory: · As an optional procedure, perform paired whole exome sequencing at baseline and progression to identify novel mutations in protein-coding genes responsible for resistant disease. If patients choose to participate, they will be consented for sample banking on protocol LAB01-473.
IRB Review and Approval Date: 10/28/2016
Recruitment Status: Closed
Projected Accrual: N/A
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Philip A. Thompson
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