Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Precision Dosing of Tyrosine Kinase Inhibitors in CML Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03885830
Recruitment Status : Active, not recruiting
First Posted : March 22, 2019
Last Update Posted : May 1, 2020
Sponsor:
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center

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.


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

Show Show detailed description

Layout table for study information
Study Type : Observational
Estimated Enrollment : 150 participants
Observational Model: Cohort
Time Perspective: Prospective
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


Group/Cohort Intervention/treatment
Bosutinib
Subjects who have been prescribed or administered bosutinib (Bosulif) for treatment of chronic-phase CML for less than 12 months.
Drug: Bosutinib
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

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

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

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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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
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.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Information from the National Library of Medicine

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


Locations
Layout table for location information
United States, North Carolina
UNC Hospital
Chapel Hill, North Carolina, United States, 27514
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
Investigators
Layout table for investigator information
Principal Investigator: Daniel Crona, PharmD, PhD University of North Carolina, Chapel Hill
Additional Information:
Layout table for additonal information
Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT03885830    
Other Study ID Numbers: LCCC1906
18-2424 ( Other Identifier: University of North Carolina IRB )
First Posted: March 22, 2019    Key Record Dates
Last Update Posted: May 1, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by UNC Lineberger Comprehensive Cancer Center:
Observational
Bosutinib
Dasatinib
Nilotinib
Imatinib
Chronic Myeloid Leukemia
CML
Pharmacokinetics
Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic-Phase
Philadelphia Chromosome
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Translocation, Genetic
Chromosome Aberrations
Pathologic Processes
Imatinib Mesylate
Dasatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action