Precision Dosing of Tyrosine Kinase Inhibitors in CML Patients
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|ClinicalTrials.gov Identifier: NCT03885830|
Recruitment Status : Recruiting
First Posted : March 22, 2019
Last Update Posted : November 19, 2020
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.
|Condition or disease||Intervention/treatment|
|CML, Chronic Phase CML (Chronic Myelogenous Leukemia CML - Philadelphia Chromosome Chronic Myeloid Leukemia Chronic Myeloid Leukemia, Chronic Phase||Drug: Bosutinib Drug: Dasatinib Drug: Imatinib Drug: Nilotinib|
|Study Type :||Observational|
|Estimated Enrollment :||150 participants|
|Official Title:||Preliminary Evaluation of TKI Exposure-response Relationships in Real World Patients (RWPs) With Chronic Myelogenous Leukemia (CML)|
|Actual Study Start Date :||June 20, 2019|
|Estimated Primary Completion Date :||December 2020|
|Estimated Study Completion Date :||December 2020|
Subjects who have been prescribed or administered bosutinib (Bosulif) for treatment of chronic-phase CML for less than 12 months.
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.
Other Name: Bosulif
Subjects who have been prescribed or administered dasatinib (Sprycel) for treatment of chronic-phase CML for less than 12 months.
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.
Other Name: Sprycel
Subjects who have been prescribed or administered imatinib (Gleevec) for treatment of chronic-phase CML for less than 12 months.
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.
Other Name: Gleevec
Subjects who have been prescribed or administered nilotinib (Tasigna) for treatment of chronic-phase CML for less than 12 months.
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.
Other Name: Tasigna
- Correlation between TKI Exposure/Clearance and BCR-ABL transcript [ Time Frame: 12 months ]TKI exposure/clearance will be evaluated by measuring levels of TKI in the blood during the 12 month study period. BCR-ABL transcripts at 12 months will be compared against the TKI levels.
- Complete Hematologic Response (CHR) [ Time Frame: 1 month ]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.
- Correlation between Early Molecular Response (EMR) and TKI Exposure/Clearance [ Time Frame: 3 months, 6 months ]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.
- Correlation between Major Molecular response (MMR) and TKI Exposure/Clearance [ Time Frame: 9 months, 12 months ]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.
- Correlation between Log10 change in BCR-ABL and TKI Exposure/Clearance [ Time Frame: Baseline and 1, 3, 6, 9, and 12 months ]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.
- Medication Adherence [ Time Frame: Baseline and 1, 3, 6, 9, and 12 months ]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.
- Correlation between Medication-induced Toxicities and TKi Exposure/Clearance [ Time Frame: Baseline and 1, 3, 6, 9, and 12 months ]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.
Biospecimen Retention: Samples With DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03885830
|Contact: Daniel Crona, PharmD, PhDfirstname.lastname@example.org|
|Contact: Benyam Muluneh, PharmD, BCOP||(984) 974-0000||Benyam.Muluneh@unchealth.unc.edu|
|United States, North Carolina|
|Chapel Hill, North Carolina, United States, 27514|
|Contact: Daniel Crona, PharmD, PhD, CPP|
|Principal Investigator:||Daniel Crona, PharmD, PhD||University of North Carolina, Chapel Hill|