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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03817398




Registration number
NCT03817398
Ethics application status
Date submitted
2/01/2019
Date registered
25/01/2019
Date last updated
12/08/2020

Titles & IDs
Public title
Stopping Tyrosine Kinase Inhibitors in Affecting Treatment-Free Remission in Patients With Chronic Phase Chronic Myeloid Leukemia
Scientific title
Stopping Tyrosine Kinase Inhibitors (TKI) to Assess Treatment-Free Remission (TFR) in Pediatric Chronic Myeloid Leukemia - Chronic Phase (CML-CP)
Secondary ID [1] 0 0
NCI-2018-03439
Secondary ID [2] 0 0
AAML18P1
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - Biospecimen Collection
Other interventions - Drug Withdrawn
Other interventions - Quality-of-Life Assessment
Other interventions - Questionnaire Administration
Treatment: Drugs - Tyrosine Kinase Inhibitor

Experimental: Basic Science (stop taking TKI, biospecimen collection) - 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.


Treatment: Surgery: Biospecimen Collection
Undergo blood collection

Other interventions: Drug Withdrawn
Stop taking TKI medication

Other interventions: Quality-of-Life Assessment
Ancillary studies

Other interventions: Questionnaire Administration
Ancillary studies

Treatment: Drugs: Tyrosine Kinase Inhibitor
Re-start TKI medicaiton

Intervention code [1] 0 0
Treatment: Surgery
Intervention code [2] 0 0
Other interventions
Intervention code [3] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Treatment-free remission (TFR) - The Kaplan Meier method will be used to estimate 2-year TFR along with a 95% confidence interval.
Timepoint [1] 0 0
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
Primary outcome [2] 0 0
Major molecular remission (MMR/MR3) - For patients re-initiating tyrosine kinase inhibitor (TKI) therapy, the cumulative incidence of major molecular remission will be calculated from the time of re-initiating TKI therapy treating deaths prior to achieving major molecular remission as competing events.
Timepoint [2] 0 0
Up to 1 year
Secondary outcome [1] 0 0
Clinical factors and laboratory correlates affecting persistence of MMR - 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.
Timepoint [1] 0 0
Up to 36 months

Eligibility
Key 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
Minimum age
No limit
Maximum age
25 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Perth Children's Hospital - Perth
Recruitment postcode(s) [1] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
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Arkansas
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United States of America
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California
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United States of America
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Colorado
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Delaware
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United States of America
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Florida
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United States of America
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Georgia
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United States of America
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Illinois
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United States of America
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Indiana
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United States of America
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Kentucky
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United States of America
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Maryland
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United States of America
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Massachusetts
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United States of America
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Michigan
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Minnesota
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United States of America
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Mississippi
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United States of America
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Missouri
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United States of America
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Nebraska
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United States of America
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New Jersey
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United States of America
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New York
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United States of America
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North Carolina
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United States of America
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Ohio
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United States of America
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Oklahoma
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United States of America
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Pennsylvania
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United States of America
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Rhode Island
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United States of America
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South Dakota
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United States of America
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Tennessee
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Texas
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Utah
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Virginia
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United States of America
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Washington
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United States of America
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Wisconsin
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Canada
State/province [32] 0 0
Nova Scotia
Country [33] 0 0
Canada
State/province [33] 0 0
Ontario

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03817398
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Sonali Chaudhury
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03817398