Preliminary Evaluation of TKI Exposure-response Relationships in Real World Patients (RWPs) With Chronic Myelogenous Leukemia (CML)

This study is a prospective, single-institution observational study designed to evaluate associations between the pharmacokinetic (PK) parameters (e.g., clearance and exposure) for four tyrosine kinase inhibitors (TKIs) used to treat chronic phase CML with key clinical milestones in CML, as well as associations between TKI PK and medication-induced toxicities and medication adherence. The four TKIs to be evaluated in this study include bosutinib, dasatinib, imatinib, or nilotinib, while the key clinical milestones for CML include complete hematologic response (CHR) at one month, early molecular response (EMR) at 3 months and 6 months, and major molecular response (MMR) at 9 months and 12 months. A total of 150 subjects will be enrolled in the study. The enrolled study subjects will have been prescribed one of these four TKIs by a UNC medical oncologist or advanced practice provider for their diagnosed chronic phase CML. Research personnel will identify potential research subjects using data from the Carolina Data Warehouse, and pharmacy prescription claims data. Research personnel will contact patients regarding study participation in-person in clinic or over the telephone to receive informed consent.

For patients who are newly initiated on a TKI, assessment procedures will occur as close to monthly time points as possible (baseline, 1,3,6,9 12, 15, etc) with at least 30 days between draws for time points at and after 3 months. For the blood collection at 1 month, there will be a +/- 2 week window. Each patient will be enrolled in the study for a maximum of 6 different study visit days, for a total of 12 total months. If a participant changes treatment to a new TKI of interest, the participant may be followed for an additional 12 months. Active participation in the study is expected to last approximately one year for these subjects. Subjects may also be identified and enrolled after having already been initiated on TKI therapy, in which case, the duration since initiation of their TKI will be 12 total months and they will enter at the closes study time point. If enrolled subjects require a change of therapy, they will restart their participation under the new TKI at baseline and be followed for an additional 12 months. Subjects who complete the 12-month study duration and subsequently change therapy may continue participation under the new TKI and restart their participation at baseline.

All study visits will align with standard-of-care follow-up appointments such that no additional research only visits to the UNCMC are required of the subjects. Up to seventy-two hours prior to each visit, one member of the study personnel will telephone (or email, if unreachable by telephone) the subject to remind them to take their medication the days prior to their study visit, but not the day of their study visit prior to blood sample collections. Subjects will also be reminded to record the exact time and date of the two doses prior to their study visit date. Subjects may resume their normal TKI dosing regimen after completion of the study visit, at the discretion of the treating provider.

At each clinic visit, the subject will have two blood samples drawn, and will be required to complete a series of surveys (Appendices D, E). Each blood sampling will collect approximately 4mL of peripheral blood, for a total of approximately 8mL of blood per study visit. Each subject will also have an additional 4mL of blood collected once at their first study visit for DNA extraction. The first research blood sample will be collected at the beginning of the clinic visit alongside the routine blood draws and processed according to the procedures listed in Appendix C. Surveys will then be administered during the visit, and lab results and clinical data will be collected. Prior to discharge, a final research blood sample will be drawn. Phlebotomy will be performed by trained phlebotomists, nurses, or physicians in the UNCMC. Blood samples will be processed per protocol by the study personnel as trained by PI or co-investigators. A detailed summary of clinic visit procedures can be found in Appendices A and B.

For subjects enrolled on the same day as their first study visit, blood samples will be drawn at the end of the study visit. All subsequent study visits will take place as described above.