SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03934372

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

An Open-Label, Single-Arm, Phase 1/2 Study Evaluating the Safety and Efficacy of Ponatinib for the Treatment of Recurrent or Refractory Leukemias or Solid Tumors in Pediatric Participants

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.

NCT03934372 Acute Myeloid Leukemia Accelerated Phase Chronic Myeloid Leukemia Blast Phase Chronic Myeloid Leukemia Chronic Phase Chronic Myeloid Leukemia Acute Lymphoblastic Leukemia Acute Lymphocytic Leukemia Leukemia Lymphoma Solid Tumors
MeSH: Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Leukemia, Lymphoid Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Myelogenous, Chronic, BCR-ABL Positive Blast Crisis Leukemia, Myeloid, Chronic-Phase Leukemia, Myeloid, Accelerated Phase
HPO: Acute megakaryocytic leukemia Acute myeloid leukemia Chronic myelogenous leukemia Leukemia Lymphoid leukemia Myeloid leukemia

1 Interventions

Name: Ponatinib

Description: Ponatinib administered as a tablet or age-appropriate formulation for pediatric participants according to age-based cohort assignment.

Type: Drug

Ponatinib


Primary Outcomes

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 days

Description: 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 months

Description: 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 months

Measure: Phase 2: Efficacy of ponatinib assessed by complete response (CR) in participants with leukemias other than BCR-ABL-positive leukemias to determine the efficacy of ponatinib

Time: 6 months

Description: 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 months

Description: 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 months

Description: 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 months

Secondary Outcomes

Measure: Phase 1: Number of treatment-emergent adverse events

Time: 6 months

Description: Time to maximum concentration.

Measure: Phase 1: Tmax of ponatinib

Time: 6 months

Description: 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 months

Description: Apparent terminal-phase disposition half-life.

Measure: Phase 1: t½ of ponatinib

Time: 6 months

Description: Apparent oral dose clearance at steady state.

Measure: Phase 1: CLss/F of ponatinib

Time: 6 months

Description: Apparent oral dose volume of distribution.

Measure: Phase 1: Vz/F of ponatinib

Time: 6 months

Description: 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 months

Description: Assessed by quantitative PCR (q-PCR).

Measure: Phase 1: MMR in participants with BCR-ABL-positive leukemias

Time: 3 months

Measure: Phase 1 and Phase 2: Complete hematologic response (CHR) in participants with CP-CML

Time: 6 months

Measure: Phase 1 and Phase 2: CCyR in participants with CP-CML

Time: 12 months

Measure: Phase 1 and Phase 2: MMR in participants with CP-CML

Time: 12 months

Description: 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 months

Description: 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 months

Description: 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 months

Description: 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 months

Measure: Phase 1: CR in participants with leukemias other than BCR-ABL-positive leukemia or CP-CML.

Time: 6 months

Description: 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 months

Description: According to Lugano criteria based on CT or MRI (or PET).

Measure: Phase 1: CR in participants with lymphoma

Time: 6 months

Description: 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 months

Measure: Phase 2: Anticancer activity of ponatinib assessed by MaHR or MMR in participants with BCR-ABL-positive leukemias (AP-CML, BP-CML or Ph+ALL)

Time: 3 months

Measure: Phase 2: Anticancer activity of ponatinib assessed by CR in participants with leukemias other than BCR-ABL-positive leukemias

Time: 6 months

Description: 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 months

Description: 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 months

Description: 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 months

Description: 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 months

Description: 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 months

Description: 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 months

Measure: Phase 2: Number of treatment-emergent adverse events

Time: 6 months

Measure: Phase 2: Clearance of pediatric-friendly formulation of ponatinib

Time: 6 months

Measure: Phase 2: Volume of distribution of pediatric-friendly formulation of ponatinib

Time: 6 months

Measure: Phase 2: AUC of pediatric-friendly formulation of ponatinib

Time: 6 months

Purpose: Treatment

Single Group Assignment


There is one SNP

SNPs


1 T315I

- 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 ---



HPO Nodes


HPO:
Acute megakaryocytic leukemia
Genes 1
GATA1
Acute myeloid leukemia
Genes 29
MPL MLF1 NSD1 JAK2 KRAS NPM1 ELANE DKC1 ETV6 TCIRG1 DNAJC21 SRP54 EFL1 FLT3 NUP214 CEBPA THPO MLLT10 RUNX1 PIGA CBFB BRCA2 KIT PICALM SBDS GFI1 SH3GL1 LPP DNMT3A
Chronic myelogenous leukemia
Genes 5
MPL BCR JAK2 KIT THPO
Leukemia
Genes 125
MPL RNASEH2B KRAS NPM1 TET2 MYD88 TSR2 RPL26 RPL27 TREX1 EFL1 PIGL SCN11A FLT3 PMS2 RPL35A EVC2 ABL1 CEBPA RARA NRAS WAS WIPF1 ATRX SH2B3 PDGFRA RB1 RNASEH2A PDGFRB CALR ARHGAP26 SH3GL1 RPS7 RPS10 NUMA1 GATA1 GATA2 RPS15A APC NSD1 ETV6 TCIRG1 DNAJC21 EVC SRP54 RPS17 NBN RPS19 SAMHD1 MSH2 RPS24 NUP214 RPS26 RPS27 RPS28 RPS29 MLLT10 RUNX1 XRCC4 CBFB CBL BCR ADAR TRIP13 ADA2 NSUN2 CREBBP PICALM GFI1 F13A1 F13B FANCA FANCC BLM FANCD2 FANCE NUTM1 JAK2 IFIH1 TYROBP MSH6 FANCG LIG4 PTPN11 SAMD9L THPO NF1 STS PIGA BRCA2 DYNC2LI1 PIK3CA SBDS GLI1 PIK3R1 BRD4 SETBP1 RNASEH2C LPP BUB1 BUB1B SCN9A SCN10A TREM2 MLF1 MLH1 ELANE DKC1 ATM HAX1 RPL35 GNB1 BUB3 CEP57 TAL1 KIT TAL2 RPL5 EP300 TP53 RPL11 KIF11 RPL15 DNMT3A RPL18
Lymphoid leukemia
Myeloid leukemia
Genes 12
GATA2 F13A1 CBL ARHGAP26 F13B KRAS PTPN11 SAMD9L KIT SETBP1 NF1 NRAS