Newswires
Preliminary Evaluation of TKI Exposure-response Relationships in Real World Patients (RWPs) With Chronic Myelogenous Leukemia (CML)
2019 APR 08 (NewsRx) -- By a
As a matter of record, on
Tracking Information
| Trial Identifier | NCT03885830 |
| First Submitted Date | |
| First Posted Date | |
| Results First Submitted Date | Not Provided |
| Results First Posted Date | Not Provided |
| Last Update Submitted Date | |
| Last Update Posted Date | |
| Primary Completion Date | |
| Start Date | |
| Current Primary Outcome Measures | •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 at 12 months. BCR-ABL transcripts at 12 months will be compared against the TKI levels. |
| Current Secondary Outcome Measures | •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. | |
| Other Outcome Measures | Not Provided |
| Change History | Complete list of historical revisions of study NCT03885830 |
Descriptive Information
| Brief Title | Precision Dosing of Tyrosine Kinase Inhibitors in CML Patients |
| Official Title | Preliminary Evaluation of TKI Exposure-response Relationships in Real World Patients (RWPs) With Chronic Myelogenous Leukemia (CML) |
| 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. |
| Detailed Description | 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 100 subjects (approximately 25 subjects per TKI) 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 |
| Study Type | Observational |
| Study Phase | Not Provided |
| Study Design | Observational Model: Cohort |
| Time Perspective: Prospective | |
| Biospecimen | Retention: Samples With DNA |
| Description: 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. | |
| Condition | CML, Chronic Phase |
| CML (Chronic Myelogenous Leukemia | |
| CML - Philadelphia Chromosome | |
| Chronic Myeloid Leukemia | |
| Chronic Myeloid Leukemia, Chronic Phase | |
| Intervention | •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 Names: | |
| ⚬Bosulif | |
| •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 Names: | |
| ⚬Sprycel | |
| •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 Names: | |
| ⚬Gleevec | |
| •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 Names: | |
| ⚬Tasigna | |
| Study Arms | •Bosutinib |
| Subjects who have been prescribed or administered bosutinib (Bosulif) for treatment of chronic-phase CML for less than 12 months. | |
| Interventions: | |
| ⚬Drug: Bosutinib | |
| •Dasatinib | |
| Subjects who have been prescribed or administered dasatinib (Sprycel) for treatment of chronic-phase CML for less than 12 months. | |
| Interventions: | |
| ⚬Drug: Dasatinib | |
| •Imatinib | |
| Subjects who have been prescribed or administered imatinib (Gleevec) for treatment of chronic-phase CML for less than 12 months. | |
| Interventions: | |
| ⚬Drug: Imatinib | |
| •Nilotinib | |
| Subjects who have been prescribed or administered nilotinib (Tasigna) for treatment of chronic-phase CML for less than 12 months. | |
| Interventions: | |
| ⚬Drug: Nilotinib |
Recruitment Information
| Recruitment Status | Not yet recruiting |
| Estimated Enrollment | 100 |
| Estimated Completion Date | |
| Primary Completion Date | |
| Eligibility | Inclusion Criteria: |
| •Patients who have signed written informed consent, Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information, and consent for storage of biospecimens. | |
| •Patients must be ≥ 18 years old. | |
| •Patients must have been diagnosed with chronic phase CML. | |
| •Patients must have adequate organ and marrow function, per the treating medical oncologist and/or advanced practice providers. | |
| •Patients must have started receiving oral chemotherapy with bosutinib, dasatinib, imatinib, or nilotinib at UNCMC on or after |
|
| •Patients are enrollment who have already been initiated on TKI therapy. They will not enter at time 0, but rather at the duration they have been prescribed the TKI (e.g., 1, 3, 6, or 9 months). Exclusion Criteria: | |
| •Patients who have cognitive impairments that could affect informed decision making. | |
| •Patients who are prescribed bosutinib, dasatinib, imatinib, or nilotinib in combination with other chemotherapy agents (e.g., hydroxyurea or omacetaxine). | |
| •Patients on active bosutinib, dasatinib, imatinib, or nilotinib therapy for over 12 months. | |
| •Patients who have achieved MMR prior to enrollment. | |
| •Patients with a confirmed T315I point mutation in BCR-ABL and/or prescribed ponatinib. | |
| •Patients who are pregnant or breastfeeding. | |
| •Patients who are incarcerated. | |
| •Patients with accelerated or blast phase CML. | |
| •Patients with diagnosed with at least one additional malignancy. | |
| Sex/Gender | Sexes Eligible for Study: All |
| Ages | 18 years and older |
| No | |
| Contacts | Primary contact: |
| Backup contact: |
|
| Listed Location Countries | Not Provided |
| Removed Location Countries |
Administrative Information
| NCT Number | NCT03885830 |
| Other Study ID Numbers | LCCC1906 |
| 18-2424 | |
| Has Data Monitoring Committee | Not Provided |
| Not Provided | |
| Plan to Share Data | No |
| Plan to Share Data (IPD) Description | Not Provided |
| Collaborators | Not Provided |
| Investigators | Principal Investigator: |
| Information Provided By | |
| Verification Date |
(Our reports deliver fact-based news of research and discoveries from around the world.)
Sandy Strickland: Call Box: Historic clock has survived a bus crash, a thief and the ravages of time
Advisor News
- Benefit Costs Squeeze Schools, Driving Cuts, Tax Hikes And Difficult Tradeoffs
- Why client insurance needs could change even if their life doesn’t
- Most Gen Z investors think less than a year ahead when making financial decisions
- IRI pitches retirement agenda to Jeffries as democrats shape affordability platform
- Help child-free clients plan for their later years
More Advisor NewsAnnuity News
- Guidance, bulletin or reg? NAIC debates form of annuity illustration update
- Nationwide adds mutual fund-linked strategy to New Heights Select FIA
- NUNN INTRODUCES BILL TO CUT RED TAPE, GIVE IOWANS CLEARER INSURANCE INFORMATION
- NAIC working group pressed to accelerate annuity illustration overhaul
- State Auditor James Brown Kicks Off Life Insurance Awareness Month With Policy Locator Tool
More Annuity NewsHealth/Employee Benefits News
Life Insurance News