Description:
This phase II 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.
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
Drug | Synonyms | Arms |
---|
Tyrosine Kinase Inhibitor | Protein Tyrosine Kinase Inhibitors, PTK Inhibitors, TK Inhibitors | Basic Science (stop taking TKI, biospecimen collection) |
Purpose
This phase II 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 molecular remission (BCR-ABL1 =<
0.1%) at 1 year after restarting TKI for children, adolescents, and young adults.
SECONDARY OBJECTIVE:
I. To describe clinical factors and laboratory correlates affecting the persistence of major
molecular remission (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
Name | Type | Description | Interventions |
---|
Basic Science (stop taking TKI, biospecimen collection) | Experimental | 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. | - 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 (MR) with a BCR-ABL1 level of =< 0.01% BCR-ABL1
as measured using the International Scale (IS) by 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 =< 0.01%
BCR-ABL1 and be able to report results in =< 2 weeks
- Patient must have received any TKI for a minimum of 3 consecutive years at time of
enrollment
- Patient agrees to discontinue TKI therapy
- REGULATORY REQUIREMENTS
- All patients and/or their parents or legal guardians must sign a written informed
consent
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met
- 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: | 25 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: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Children's Oncology Group |
Last Updated
August 25, 2021