SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT01207440

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

A Pivotal Phase 2 Trial of Ponatinib (AP24534) in Patients With Refractory Chronic Myeloid Leukemia and Ph+ Acute Lymphoblastic Leukemia

The purpose of this study is to determine the efficacy of ponatinib in patients with chronic myeloid leukemia (CML) in chronic phase (CP), accelerated phase (AP) or blast phase (BP) or with Ph positive (Ph+) acute lymphoblastic leukemia (ALL) who either are resistant or intolerant to either dasatinib or nilotinib, or have the T315I mutation.

NCT01207440 Chronic Myeloid Leukemia Ph+ Acute Lymphoblastic Leukemia
MeSH: Leukemia Leukemia, Myeloid Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Leukemia, Myelogenous, Chronic, BCR-ABL Positive
HPO: Chronic myelogenous leukemia Leukemia Lymphoid leukemia Myeloid leukemia

1 Interventions

Name: Ponatinib

Description: 45 mg dose taken orally once daily

Type: Drug

CP-CML R/I AP-CML R/I Blast Phase (BP) CML / Ph+ ALL CP-CML with T315I mutation AP-CML with T315I mutation BP-CML / Ph+ ALL with T315I mutation


Primary Outcomes

Description: Defined as complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR).

Measure: Major cytogenetic response (MCyR) in CP-CML patients

Time: up to 48 months after first dose

Description: Consists of complete hematologic response (CHR) or no evidence of leukemia (NEL)

Measure: Major hematologic response (MaHR) in AP-CML patients

Time: up to 48 months after first dose

Description: Consists of CHR or NEL

Measure: MaHR in BP-CML/Ph+ALL patients

Time: up to 48 months after first dose

Secondary Outcomes

Description: The composite of: Hematologic responses: CHR; Cytogenetic responses: confirmed MCyR; and Molecular response: major molecular response (MMR).

Measure: Responses in CP-CML patients

Time: up to 48 months after first dose

Description: The composite of: Cytogenetic responses: CCyR, PCyR, confirmed MCyR; and Molecular response: MMR.

Measure: Responses in AP-CML or BP-CML/Ph+ ALL patients

Time: up to 48 months after first dose

Description: The composite of time to response, duration of response, progression free survival, and overall survival.

Measure: Responses in all patients

Time: up to 48 months after first dose

Description: The Adverse Event (AE) incidence rates as well as the frequency of occurrence of overall toxicity, categorized by toxicity grades (severity) will be described for each cohort of the trial. Listings of laboratory test results will also be generated, and descriptive statistics summarizing the changes in laboratory tests over time will be presented.

Measure: Safety and tolerability for all patients

Time: up to 48 months after first dose

Purpose: Treatment

Allocation: Non-Randomized

Single Group Assignment


There is one SNP

SNPs


1 T315I

Ponatinib for Chronic Myeloid Leukemia (CML) Evaluation and Ph+ Acute Lymphoblastic Leukemia (ALL) The purpose of this study is to determine the efficacy of ponatinib in patients with chronic myeloid leukemia (CML) in chronic phase (CP), accelerated phase (AP) or blast phase (BP) or with Ph positive (Ph+) acute lymphoblastic leukemia (ALL) who either are resistant or intolerant to either dasatinib or nilotinib, or have the T315I mutation. --- T315I ---

- Have active Central Nervous System (CNS) disease - Have significant or active cardiovascular disease - Have a significant bleeding disorder unrelated to CML or Ph+ALL - Have a history of pancreatitis or alcohol abuse - Have uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL) - Have malabsorption syndrome or other gastrointestinal illness that could affect absorption of ponatinib - Diagnosed with another primary malignancy in the past 3 years - Pregnant or lactating - Underwent major surgery within 14 days prior to first dose of ponatinib - Have ongoing or active infection - Suffer from any other condition or illness that would compromise safety or interfere with evaluation of the drug Chronic Myeloid Leukemia Ph+ Acute Lymphoblastic Leukemia Leukemia Leukemia, Myeloid Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Leukemia, Myelogenous, Chronic, BCR-ABL Positive The preliminary analysis of the phase 1 clinical trial revealed evidence of clinical antitumor activity in patients with resistance to approved second-generation tyrosine kinase inhibitors (TKI), dasatinib and nilotinib, including patients with the T315I mutation of the BCR-ABL gene (BCR-ABL). --- T315I ---

This Phase 1 study, taken together with the strong preclinical data that characterize ponatinib, provides the rationale for moving to a pivotal phase 2 trial of this agent in a population of patients with chronic myeloid leukemia (CML) and Ph+ Acute Lymphoblastic Leukemia (ALL) who are resistant or intolerant to prior TKI therapy and in those patients with the T315I mutation. --- T315I ---



HPO Nodes


HPO:
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