Clinical Trials /

Stopping Tyrosine Kinase Inhibitors in Affecting Treatment-Free Remission in Patients With Chronic Phase Chronic Myeloid Leukemia

NCT03817398

Description:

This trial studies how stopping tyrosine kinase inhibitors will affect treatment-free remission in patients with chronic myeloid leukemia in chronic phase. When the level of disease is very low, it's called molecular remission. TKIs are a type of medication that help keep this level low. However, after being in molecular remission for a specific amount of time, it may not be necessary to take tyrosine kinase inhibitors. It is not yet known whether stopping tyrosine kinase inhibitors will help patients with chronic myeloid leukemia in chronic phase continue or re-achieve molecular remission.

Related Conditions:
  • Chronic Myeloid Leukemia
Recruiting Status:

Not yet recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Stopping Tyrosine Kinase Inhibitors in Affecting Treatment-Free Remission in Patients With Chronic Phase Chronic Myeloid Leukemia
  • Official Title: Stopping Tyrosine Kinase Inhibitors (TKI) to Assess Treatment-Free Remission (TFR) in Pediatric Chronic Myeloid Leukemia - Chronic Phase (CML-CP)

Clinical Trial IDs

  • ORG STUDY ID: AAML18P1
  • SECONDARY ID: NCI-2018-03439
  • SECONDARY ID: AAML18P1
  • SECONDARY ID: AAML18P1
  • SECONDARY ID: U10CA180886
  • NCT ID: NCT03817398

Conditions

  • Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive

Interventions

DrugSynonymsArms
Tyrosine Kinase InhibitorProtein Tyrosine Kinase Inhibitors, PTK Inhibitors, TK InhibitorsBasic Science (stop taking TKI, biospecimen collection)

Purpose

This trial studies how stopping tyrosine kinase inhibitors will affect treatment-free remission in patients with chronic myeloid leukemia in chronic phase. When the level of disease is very low, it's called molecular remission. TKIs are a type of medication that help keep this level low. However, after being in molecular remission for a specific amount of time, it may not be necessary to take tyrosine kinase inhibitors. It is not yet known whether stopping tyrosine kinase inhibitors will help patients with chronic myeloid leukemia in chronic phase continue or re-achieve molecular remission.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the 2-year treatment free remission (TFR) rate of children, adolescents, and
      young adults with chronic myeloid leukemia - chronic phase (CML-CP) following discontinuation
      tyrosine kinase inhibitor (TKI).

      II. To estimate the re-induction rate and maintenance of major molecular remission (MMR/MR3)
      at 1 year after restarting TKI for children, adolescents, and young adults.

      SECONDARY OBJECTIVES:

      I. To describe clinical factors and laboratory correlates affecting the persistence of MMR
      and re-initiation of treatment after stopping TKI (e.g. patient demographics, duration and
      level of prior molecular remission, duration and type of TKI, clinical presentation at
      diagnosis and immune studies).

      EXPLORATORY OBJECTIVES:

      I. To describe change in height standard deviation score over time in patients who are able
      to discontinue their TKI.

      II. To describe the long-term health outcomes including but not limited to gonadal function,
      endocrine function, and bone metabolism in patients who are able to discontinue TKI as well
      as those that need to restart TKIs.

      III. To describe differences in patient-reported health status after stopping TKIs, including
      those who need to resume TKI after stopping.

      IV. To describe the incidence and characteristics of TKI withdrawal syndrome in children.

      V. To evaluate changes in neurocognitive outcomes of patients enrolled on this study using a
      patient-completed, performance-based, computerized measure of neuropsychological functioning
      and a parent-report/self-report questionnaire.

      OUTLINE:

      Patients stop taking TKI medication within 10 days after enrollment. Patients undergo
      peripheral blood collection to monitor loss of MMR every 4 weeks in year 1, every 6 weeks in
      year 2, and every 12 weeks in year 3. Patients who lose their molecular remission may restart
      TKI medication and are monitored every 4 weeks in year 1, every 6 weeks in year 2, and every
      12 weeks in year 3.

      After completion of study treatment, patients are followed up annually.
    

Trial Arms

NameTypeDescriptionInterventions
Basic Science (stop taking TKI, biospecimen collection)ExperimentalPatients stop taking TKI medication within 10 days after enrollment. Patients undergo peripheral blood collection to monitor loss of MMR every 4 weeks in year 1, every 6 weeks in year 2, and every 12 weeks in year 3. Patients who lose their molecular remission may restart TKI medication and are monitored every 4 weeks in year 1, every 6 weeks in year 2, and every 12 weeks in year 3.
  • Tyrosine Kinase Inhibitor

Eligibility Criteria

        Inclusion Criteria:

          -  Patient must have been diagnosed with CML-CP at < 18 years of age.

          -  Patient must have histologic verification of CML-CP at original diagnosis

          -  Patient must be in molecular remission with at least a MR4 (< 0.01% BCR-ABL1
             (International Scale [IS]) level by real-time quantitative-polymerase chain reaction
             [RQ-PCR]) for >= 2 consecutive years at the time of enrollment

               -  Please note: The lab evaluating disease status and molecular response for this
                  study must be College of American Pathology (CAP) and/or Clinical Laboratory
                  Improvement Amendments (CLIA) certified (United States [US] only), sites in other
                  countries must be certified by their accredited authorities. All labs must use
                  the International Scale guidelines with a sensitivity of detection assay < MR4
                  and be able to report results in =< 2 weeks

          -  Patient must have received their current TKI for a minimum of 3 consecutive years at
             time of enrollment

          -  Patient agrees to discontinue TKI therapy

          -  ELIGIBILITY FOR PATIENT-REPORTED OUTCOMES (PROs):

          -  Age >= 8 years at the time of enrollment

          -  Ability to understand English or Spanish

          -  Cognitive ability to complete instruments according to the primary team

          -  ELIGIBILITY FOR AAML18P1 NEUROCOGNITIVE STUDY:

          -  Patient must be 5 years or older at the time of enrollment

          -  English-, French- or Spanish-speaking

          -  No known history of neurodevelopmental disorder prior to diagnosis of CML (e.g., Down
             syndrome, Fragile X, William syndrome, mental retardation)

          -  No significant visual or motor impairment that would prevent computer use or
             recognition of visual test stimuli

        Exclusion Criteria:

          -  Known T3151 mutation

          -  Additional clonal chromosomal abnormalities in Philadelphia chromosome (Ph) positive
             (+) cells at any time prior to enrollment that include ?major route? abnormalities
             (second Ph, trisomy 8, isochromosome 17q, trisomy 19), complex karyotype or
             abnormalities of 3q26.2

          -  History of accelerated phase or blast crisis CML

          -  Female patients who are pregnant

          -  Lactating females are not eligible unless they have agreed not to breastfeed their
             infants

          -  Female patients of childbearing potential are not eligible unless a negative pregnancy
             test result has been obtained
      
Maximum Eligible Age:24 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Treatment-free remission (TFR)
Time Frame:From date of TKI discontinuation to the date of the first event (molecular recurrence, hematologic relapse, cytogenetic relapse, re-initiation of TKI therapy, second malignant neoplasm, or death) or censoring, assessed up to 2 years
Safety Issue:
Description:The Kaplan Meier method will be used to estimate 2-year TFR along with a 95% confidence interval.

Secondary Outcome Measures

Measure:Clinical factors and laboratory correlates affecting persistence of MMR
Time Frame:Up to 36 months
Safety Issue:
Description:Clinical factors and laboratory correlates (e.g. duration and level of prior molecular remission, risk score, duration and type of TKI, disease scoring system and immune studies etc.) affecting persistence of MMR and re-initiation of treatment after stopping TKI will be assessed by Cox proportional hazard regression models.

Details

Phase:N/A
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Children's Oncology Group

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