The purpose of this prospective, single-institution observational study is to evaluate associations between the pharmacokinetic (PK) parameters for tyrosine kinase inhibitors (TKIs) used to treat chronic phase chronic myeloid leukemia (CML) and clinical outcomes for up to 12 months. The study aims to identify associations between TKI clearance and/or exposure with demographic and clinical patient characteristics, CML milestones, medication toxicities, medication adherence, and germline genetic variants. Because this is an observational study, standard-of-care therapy will not be altered during the course of participation. Blood samples will be collected at each study visit (up to 6 visits) over the course of 12 months to evaluate TKI concentrations, and PK parameters. Blood will also be collected during the first visit to isolate DNA for next generation sequencing (NGS). Demographic information will be collected at baseline, while clinical and medication adherence information will be collected at baseline and then throughout the study. There will be no direct benefit to you for your participation. Risks are minor, but could include bruising, vein irritation, lightheadedness/dizziness, and/or infection from blood draws, as well as potential loss of confidentiality.
Name: Bosutinib
Description: Subjects will be enrolled into this group if they are receiving bosutinib per standard of care. This is an observational study and no interventions will be made.Type: DrugBosutinib
Name: Dasatinib
Description: Subjects will be enrolled into this group if they are receiving dasatinib per standard of care. This is an observational study and no interventions will be made.Type: DrugDasatinib
Name: Imatinib
Description: Subjects will be enrolled into this group if they are receiving imatinib per standard of care. This is an observational study and no interventions will be made.Type: DrugImatinib
Name: Nilotinib
Description: Subjects will be enrolled into this group if they are receiving nilotinib per standard of care. This is an observational study and no interventions will be made.Type: DrugNilotinib
Description: TKI exposure/clearance will be evaluated by measuring levels of TKI in the blood at 12 months. BCR-ABL transcripts at 12 months will be compared against the TKI levels.
Measure: Correlation between TKI Exposure/Clearance and BCR-ABL transcript Time: 12 monthsDescription: CHR at 1 month, defined as complete normalization of peripheral blood counts with leukocyte count < 10 x 1E9/L, platelet count < 450 x 1E9/L, no immature cells (such as myelocytes, promyelocytes, no blasts in peripheral blood, and no signs and symptoms of disease with disappearance of palpable splenomegaly.
Measure: Complete Hematologic Response (CHR) Time: 1 monthDescription: Incidence of EMR at 3 and 6 months, defined as BCR-ABL transcript ≤ 10%, will be evaluated, and will be compared against TKI levels at 3 and 6 months.
Measure: Correlation between Early Molecular Response (EMR) and TKI Exposure/Clearance Time: 3 months, 6 monthsDescription: Incidence of MMR at 9 and 12 months, defined as BCR-ABL transcript ≤ 0.1%, will be evaluated, and will be compared against TKI levels at 9 and 12 months.
Measure: Correlation between Major Molecular response (MMR) and TKI Exposure/Clearance Time: 9 months, 12 monthsDescription: BCR-ABL transcripts will be obtained at each time point. The Log10 change in BCR-ABL transcripts will be evaluated, and will be compared against TKI levels at each time point.
Measure: Correlation between Log10 change in BCR-ABL and TKI Exposure/Clearance Time: Baseline and 1, 3, 6, 9, and 12 monthsDescription: Subject adherence will be evaluated at each time point during standard-of-care study visits. The Wilson's 3-item Adherence Score (WAS) tool will be administered to each subject at each visit in survey form. The WAS tool provides a score from 0-100 (0, worst; 100, best) to evaluate adherence to medications in the last 30 days.
Measure: Medication Adherence Time: Baseline and 1, 3, 6, 9, and 12 monthsDescription: Associate TKI exposure/clearance with subject-reported toxicity assessments. Medication-induced toxicity assessments will be conducted at each study visit using the validated MD Anderson Symptom Inventory for CML (MDASI-CML) tool. The MDASI-CML tool asks subjects to rate symptom severity in the last 24 hours on a 0-10 scale (0, not present; 10, as bad as one can imagine). The MDASI-CML also evaluates symptom interference with daily activities in the same manner.
Measure: Correlation between Medication-induced Toxicities and TKi Exposure/Clearance Time: Baseline and 1, 3, 6, 9, and 12 monthsCohort
There is one SNP
- Patients with a confirmed T315I point mutation in BCR-ABL and/or prescribed ponatinib. --- T315I ---