Precision Dosing of Tyrosine Kinase Inhibitors in CML Patients

NCT03885830 | Completed

• 2 other identifiers: LCCC190618-2424
• Study Type: observational
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

CML, Chronic Phase; CML (Chronic Myelogenous Leukemia; CML - Philadelphia Chromosome; Chronic Myeloid Leukemia; Chronic Myeloid Leukemia, Chronic Phase

Keywords

Observational; Bosutinib; Dasatinib; Nilotinib; Imatinib; Chronic Myeloid Leukemia; CML; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Correlation between TKI Exposure/Clearance and BCR-ABL transcript

  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.

  12 months

Secondary Outcomes (6)

• Complete Hematologic Response (CHR)

  1 month

• Correlation between Early Molecular Response (EMR) and TKI Exposure/Clearance

  3 months, 6 months

• Correlation between Major Molecular response (MMR) and TKI Exposure/Clearance

  9 months, 12 months

• Correlation between Log10 change in BCR-ABL and TKI Exposure/Clearance

  Baseline and 1, 3, 6, 9, and 12 months

• Medication Adherence

  Baseline and 1, 3, 6, 9, and 12 months

Study Arms (4)

Bosutinib

Subjects who have been prescribed or administered bosutinib (Bosulif) for treatment of chronic-phase CML for less than 12 months.

Drug: Bosutinib

Dasatinib

Subjects who have been prescribed or administered dasatinib (Sprycel) for treatment of chronic-phase CML for less than 12 months.

Drug: Dasatinib

Imatinib

Subjects who have been prescribed or administered imatinib (Gleevec) for treatment of chronic-phase CML for less than 12 months.

Drug: Imatinib

Nilotinib

Subjects who have been prescribed or administered nilotinib (Tasigna) for treatment of chronic-phase CML for less than 12 months.

Drug: Nilotinib

Interventions

Bosutinib DRUG

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.

Also known as: Bosulif

Bosutinib

Dasatinib DRUG

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.

Also known as: Sprycel

Dasatinib

Imatinib DRUG

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.

Also known as: Gleevec

Imatinib

Nilotinib DRUG

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.

Also known as: Tasigna

Nilotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This prospective, single-institution observational study is 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 eligible for this study include bosutinib, dasatinib, imatinib, or nilotinib. 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 their UNC medical oncologist or advanced practice provider for their diagnosed chronic phase CML.

You may qualify if:

• Patients who have signed written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information
• Patients must be ≥ 18 years old.
• Patients must have been diagnosed with chronic phase CML.
• Patients who will start or have already started receiving oral chemotherapy with bosutinib, dasatinib, imatinib, or nilotinib for their diagnosis of CML.

You may not qualify if:

• Patients who have cognitive impairments that could affect informed decision making.
• Patients who are prescribed bosutinib, dasatinib, imatinib, or nilotinib in combination with other chemotheapy agents (e.g., hydroxyurea or omacetaxine).
• Patients who have undetectable BCR-ABL transcripts.
• Patients with a confirmed T315I point mutation in BCR-ABL and/or prescribed ponatinib.
• Patients who are incarcerated.
• Patients with accelerated or blast phase CML.
• Patients diagnosed with, or currently undergoing treatment for a concurrent second primary malignancy.

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead

Study Sites (1)

UNC Hospital

Chapel Hill, North Carolina, 27514, United States

Location

Related Links

• UNC Lineberger Comprehensive Cancer Center Clinical Trials

Biospecimen

Retention: SAMPLES WITH DNA

For all study subjects, two blood samples will be taken at each study visit. These samples will be used to quantify TKI concentrations in the plasma. Later, the TKI concentration/time information will be used in PK analyses that will estimate clearance and exposure. Additionally, during the subject's first study, an additional blood sample will be obtained to isolate DNA for NGS. Throughout the study, all blood samples will be collected by a phlebotomist or nurse.

MeSH Terms

Conditions

Leukemia, Myeloid, Chronic-Phase; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

bosutinib; Dasatinib; Imatinib Mesylate; nilotinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Benzamides; Amides; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines

Study Officials

• Daniel Crona, PharmD, PhD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2019
• First Posted: March 22, 2019
• Study Start: June 20, 2019
• Primary Completion: June 15, 2022
• Study Completion: June 15, 2022
• Last Updated: January 11, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)