The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and efficacy of ponatinib in children aged 1 to < 18 years with advanced leukemias, lymphomas, and solid tumors.
Name: Ponatinib
Description: Ponatinib administered as a tablet or age-appropriate formulation for pediatric participants according to age-based cohort assignment.Type: DrugPonatinib
Description: Defined as the occurrence of any protocol-defined toxicities occurring after dosing and up to and including Day 28, except those toxicities with a clear alternative explanation.
Measure: Phase 1: Number of dose-limiting toxicities Time: 28 daysDescription: Defined as complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR) as assessed by conventional cytogenetics or fluorescence in situ hybridization (FISH).
Measure: Phase 2: Efficacy of ponatinib assessed by major cytogenetic response (MCyR) in participants with chronic-phase chronic myeloid leukemia (CP-CML) Time: 12 monthsDescription: Assessed by polymerase chain reaction (PCR).
Measure: Phase 2: Efficacy of ponatinib assessed by major hematologic response (MaHR) or major molecular response (MMR) in participants with BCR-ABL-positive leukemias Time: 3 monthsDescription: Assessed by conventional cytogenetics, FISH, or PCR.
Measure: Phase 2: Efficacy of ponatinib assessed by incomplete complete response (iCR) in participants with leukemias other than BCR-ABL-positive leukemias Time: 6 monthsDescription: According to Lugano criteria based on computed tomography (CT) or magnetic resonance imaging (MRI) (or positron emission tomography [PET]).
Measure: Phase 2: Efficacy of ponatinib assessed by CR in participants with lymphoma Time: 6 monthsDescription: Defined as the percentage of participants having CR or PR, as determined by investigator assessment of radiographic disease per tumors per RANO for central nervous system (CNS) tumors or Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) for other solid tumors based on CT or MRI (or PET).
Measure: Phase 2: Efficacy of ponatinib assessed by overall response rate in participants with solid tumors Time: 6 monthsDescription: Time to maximum concentration.
Measure: Phase 1: Tmax of ponatinib Time: 6 monthsDescription: Area under the steady-state plasma or serum concentration-time curve from Hour 0 to 24.
Measure: Phase 1: AUCss,0-24 of ponatinib Time: 6 monthsDescription: Apparent terminal-phase disposition half-life.
Measure: Phase 1: t½ of ponatinib Time: 6 monthsDescription: Apparent oral dose clearance at steady state.
Measure: Phase 1: CLss/F of ponatinib Time: 6 monthsDescription: Apparent oral dose volume of distribution.
Measure: Phase 1: Vz/F of ponatinib Time: 6 monthsDescription: Defined as CCyR or PCyR as assessed by conventional cytogenetics or FISH.
Measure: Phase 1: MCyR in participants with BCR-ABL-positive leukemias Time: 3 monthsDescription: Assessed by quantitative PCR (q-PCR).
Measure: Phase 1: MMR in participants with BCR-ABL-positive leukemias Time: 3 monthsDescription: Defined as the interval from the date of the first dose of study treatment to first response.
Measure: Phase 1 and Phase 2: Time to response (TTR) in participants with CP-CML Time: 6 monthsDescription: Defined as the interval between the first assessment at which the criteria for response are met until the criteria for progression are met.
Measure: Phase 1 and Phase 2: Duration of response (DOR) in participants with CP-CML Time: 6 monthsDescription: Defined as the interval from the date of the first dose of study treatment until the date of progression of disease or the date of death from any cause, whichever is earlier.
Measure: Phase 1 and Phase 2: Progression-free survival (PFS) in participants with CP-CML Time: 6 monthsDescription: Defined as the interval from the date of the first dose of study treatment until death from any cause.
Measure: Phase 1 and Phase 2: Overall survival (OS) in participants with CP-CML Time: 6 monthsDescription: Assessed by conventional cytogenetics, FISH, or q-PCR.
Measure: Phase 1: CRi in participants with leukemias other than BCR-ABL-positive leukemia or CP-CML Time: 6 monthsDescription: According to Lugano criteria based on CT or MRI (or PET).
Measure: Phase 1: CR in participants with lymphoma Time: 6 monthsDescription: Defined as the percentage of participants having CR or PR, as determined by investigator assessment of radiographic disease per tumors per RANO for CNS tumors or RECIST v1.1 for other solid tumors based on CT or MRI (or PET).
Measure: Phase 1: Overall response rate in participants with solid tumors Time: 6 monthsDescription: Assessed by conventional cytogenetics, FISH, or PCR.
Measure: Phase 2: Anticancer activity of ponatinib assessed by CRi in participants with leukemias other than BCR-ABL-positive leukemias. Time: 6 monthsDescription: According to Lugano criteria based on CT or MRI (or PET).
Measure: Phase 2: Anticancer activity of ponatinib assessed by CR in participants with lymphoma Time: 6 monthsDescription: Defined as the percentage of participants having CR or PR, as determined by investigator assessment of radiographic disease per tumors per RANO for CNS tumors or RECIST v1.1 for other solid tumors based on CT or MRI (or PET).
Measure: Phase 2: Anticancer activity of ponatinib assessed by overall response rate in participants with solid tumors Time: 6 monthsDescription: Defined as the interval from the date of the first dose of study treatment until death from any cause.
Measure: Phase 2: OS in participants with solid tumors Time: 6 monthsDescription: Defined as the interval between the first assessment at which the criteria for response are met until the criteria for progression are met.
Measure: Phase 2: DOR in participants with solid tumors Time: 6 monthsDescription: Defined as the interval from the date of the first dose of study treatment until the date of progression of disease or the date of death from any cause, whichever is earlier.
Measure: Phase 2: PFS in participants with solid tumors Time: 6 monthsSingle Group Assignment
There is one SNP
- Phase 2 (CP-CML): Participants who are resistant to or intolerant of at least 1 prior BCR-ABL-targeted TKI therapy or have the T315I kinase domain mutation. --- T315I ---