Stopping Tyrosine Kinase Inhibitors (TKI) to Assess Treatment-Free Remission (TFR) in Pediatric Chronic Myeloid Leukemia - Chronic Phase (CML-CP)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 110
- 试验地点
- 301
- 主要终点
- Treatment-free remission (TFR)
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 25 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Tyrosine Kinase Inhibitor (Drug)
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.
干预措施: Quality-of-Life Assessment (Other)
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.
干预措施: Biospecimen Collection (Procedure)
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.
干预措施: Drug Withdrawn (Other)
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.
干预措施: Questionnaire Administration (Other)
结局指标
主要结局
Treatment-free remission (TFR)
时间窗: 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
The Kaplan Meier method will be used to estimate 2-year TFR along with a 95% confidence interval.
Major molecular remission (MMR/MR3)
时间窗: Up to 1 year
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.
次要结局
- Clinical factors and laboratory correlates affecting persistence of MMR(Up to 36 months)