The purposes of this study are to investigate expression and frequency of ABL point mutations, a major cause of resistance in imatinib failed CML Asian patients and to find causes of Asian-specific resistance to cancer-targeting therapies through a prospective investigation of dynamics of point mutations and expression of new point mutations during nilotinib treatment.
Name: Nilotinib
Case-Control
There are 9 SNPs
With regard to peculiar point mutations, V299L, F317L, and E25K/V show relative resistance to dasatinib, and p-loop mutations including G250E, Q252H, Y253F/H and E255K/V and F359C/V show relative resistance to nilotinib. --- V299L --- --- F317L --- --- E25K --- --- G250E --- --- Q252H --- --- Y253F --- --- E255K ---
With regard to peculiar point mutations, V299L, F317L, and E25K/V show relative resistance to dasatinib, and p-loop mutations including G250E, Q252H, Y253F/H and E255K/V and F359C/V show relative resistance to nilotinib. --- V299L --- --- F317L --- --- E25K ---
With regard to peculiar point mutations, V299L, F317L, and E25K/V show relative resistance to dasatinib, and p-loop mutations including G250E, Q252H, Y253F/H and E255K/V and F359C/V show relative resistance to nilotinib. --- V299L --- --- F317L ---
With regard to peculiar point mutations, V299L, F317L, and E25K/V show relative resistance to dasatinib, and p-loop mutations including G250E, Q252H, Y253F/H and E255K/V and F359C/V show relative resistance to nilotinib. --- V299L --- --- F317L --- --- E25K --- --- G250E --- --- Q252H --- --- Y253F --- --- E255K --- --- F359C ---
With regard to peculiar point mutations, V299L, F317L, and E25K/V show relative resistance to dasatinib, and p-loop mutations including G250E, Q252H, Y253F/H and E255K/V and F359C/V show relative resistance to nilotinib. --- V299L --- --- F317L --- --- E25K --- --- G250E ---
With regard to peculiar point mutations, V299L, F317L, and E25K/V show relative resistance to dasatinib, and p-loop mutations including G250E, Q252H, Y253F/H and E255K/V and F359C/V show relative resistance to nilotinib. --- V299L --- --- F317L --- --- E25K --- --- G250E --- --- Q252H ---
Inclusion Criteria: - Patients with Philadelphia chromosome-positive or BCR-ABL positive CML - Chronic, Accelerated phase CML patients who show an inappropriate response to the imatinib treatment or failed the treatment according to ELN 2009 RECOMMENDATION - Patients with ECOG performance status of 0-3 - Patients who consent to the use of study information and study specimen Exclusion Criteria: - Patients with diseases other than CML - Patients treated with myelosuppressive anticancer therapy other than Hydroxyurea and Angrelide - Patients who have been treated with second-generation cancer-targeting drug - Patients who do not consent to the use of study information and study specimen - Previously documented T315I mutation - Impaired cardiac function including any of the following: LVEF by echocardiography < 45% or below the institutional lower range (whichever is greater); complete left bundle branch block; long QT syndrome or family history of; history or presence of significant ventricular or atrial tachyarrhythmias; clinically significant brachycardia (< 50 bpm); QTcF > 450 msec at baseline; right bundle branch block plus left anterior hemiblock; bifascicular block; myocardial infarction ≤ 12 months; uncontrolled angina; other clinically significant heart disease (e.g., congestive heart failure) - Treatment with strong inhibitors of CYP3A4 or medication that are well documented to prolong the QT interval are contraindicated - Impaired gastrointestinal(GI)function or GI disease that may significantly alter the absorption of the study drug (e.g., ulcerative diseases, uncontrolled nausea, vomitting, diarrhea, malabsorption syndrome, small bowel resection or gastric bypass surgery) - History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis - Know cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required) - Patients who previously had a bone marrow or stem cell transplantation - Pregnant or breast-feeding patients - Hypersensitivity to nilotinib or any of the excipients - The capsules contain lactose, and nilotinib is therefore not recommended for patients with rare hereditary problem of galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption Inclusion Criteria: - Patients with Philadelphia chromosome-positive or BCR-ABL positive CML - Chronic, Accelerated phase CML patients who show an inappropriate response to the imatinib treatment or failed the treatment according to ELN 2009 RECOMMENDATION - Patients with ECOG performance status of 0-3 - Patients who consent to the use of study information and study specimen Exclusion Criteria: - Patients with diseases other than CML - Patients treated with myelosuppressive anticancer therapy other than Hydroxyurea and Angrelide - Patients who have been treated with second-generation cancer-targeting drug - Patients who do not consent to the use of study information and study specimen - Previously documented T315I mutation - Impaired cardiac function including any of the following: LVEF by echocardiography < 45% or below the institutional lower range (whichever is greater); complete left bundle branch block; long QT syndrome or family history of; history or presence of significant ventricular or atrial tachyarrhythmias; clinically significant brachycardia (< 50 bpm); QTcF > 450 msec at baseline; right bundle branch block plus left anterior hemiblock; bifascicular block; myocardial infarction ≤ 12 months; uncontrolled angina; other clinically significant heart disease (e.g., congestive heart failure) - Treatment with strong inhibitors of CYP3A4 or medication that are well documented to prolong the QT interval are contraindicated - Impaired gastrointestinal(GI)function or GI disease that may significantly alter the absorption of the study drug (e.g., ulcerative diseases, uncontrolled nausea, vomitting, diarrhea, malabsorption syndrome, small bowel resection or gastric bypass surgery) - History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis - Know cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required) - Patients who previously had a bone marrow or stem cell transplantation - Pregnant or breast-feeding patients - Hypersensitivity to nilotinib or any of the excipients - The capsules contain lactose, and nilotinib is therefore not recommended for patients with rare hereditary problem of galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption Chronic Myeloid Leukemia Leukemia, Myelogenous, Chronic, BCR-ABL Positive Recently the treatment strategy of Philadelphia chromosome-positive leukemia has undergone groundbreaking changes due to the development of new second-generation cancer-targeting drugs. --- T315I ---
Inclusion Criteria: - Patients with Philadelphia chromosome-positive or BCR-ABL positive CML - Chronic, Accelerated phase CML patients who show an inappropriate response to the imatinib treatment or failed the treatment according to ELN 2009 RECOMMENDATION - Patients with ECOG performance status of 0-3 - Patients who consent to the use of study information and study specimen Exclusion Criteria: - Patients with diseases other than CML - Patients treated with myelosuppressive anticancer therapy other than Hydroxyurea and Angrelide - Patients who have been treated with second-generation cancer-targeting drug - Patients who do not consent to the use of study information and study specimen - Previously documented T315I mutation - Impaired cardiac function including any of the following: LVEF by echocardiography < 45% or below the institutional lower range (whichever is greater); complete left bundle branch block; long QT syndrome or family history of; history or presence of significant ventricular or atrial tachyarrhythmias; clinically significant brachycardia (< 50 bpm); QTcF > 450 msec at baseline; right bundle branch block plus left anterior hemiblock; bifascicular block; myocardial infarction ≤ 12 months; uncontrolled angina; other clinically significant heart disease (e.g., congestive heart failure) - Treatment with strong inhibitors of CYP3A4 or medication that are well documented to prolong the QT interval are contraindicated - Impaired gastrointestinal(GI)function or GI disease that may significantly alter the absorption of the study drug (e.g., ulcerative diseases, uncontrolled nausea, vomitting, diarrhea, malabsorption syndrome, small bowel resection or gastric bypass surgery) - History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis - Know cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required) - Patients who previously had a bone marrow or stem cell transplantation - Pregnant or breast-feeding patients - Hypersensitivity to nilotinib or any of the excipients - The capsules contain lactose, and nilotinib is therefore not recommended for patients with rare hereditary problem of galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption Inclusion Criteria: - Patients with Philadelphia chromosome-positive or BCR-ABL positive CML - Chronic, Accelerated phase CML patients who show an inappropriate response to the imatinib treatment or failed the treatment according to ELN 2009 RECOMMENDATION - Patients with ECOG performance status of 0-3 - Patients who consent to the use of study information and study specimen Exclusion Criteria: - Patients with diseases other than CML - Patients treated with myelosuppressive anticancer therapy other than Hydroxyurea and Angrelide - Patients who have been treated with second-generation cancer-targeting drug - Patients who do not consent to the use of study information and study specimen - Previously documented T315I mutation - Impaired cardiac function including any of the following: LVEF by echocardiography < 45% or below the institutional lower range (whichever is greater); complete left bundle branch block; long QT syndrome or family history of; history or presence of significant ventricular or atrial tachyarrhythmias; clinically significant brachycardia (< 50 bpm); QTcF > 450 msec at baseline; right bundle branch block plus left anterior hemiblock; bifascicular block; myocardial infarction ≤ 12 months; uncontrolled angina; other clinically significant heart disease (e.g., congestive heart failure) - Treatment with strong inhibitors of CYP3A4 or medication that are well documented to prolong the QT interval are contraindicated - Impaired gastrointestinal(GI)function or GI disease that may significantly alter the absorption of the study drug (e.g., ulcerative diseases, uncontrolled nausea, vomitting, diarrhea, malabsorption syndrome, small bowel resection or gastric bypass surgery) - History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis - Know cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required) - Patients who previously had a bone marrow or stem cell transplantation - Pregnant or breast-feeding patients - Hypersensitivity to nilotinib or any of the excipients - The capsules contain lactose, and nilotinib is therefore not recommended for patients with rare hereditary problem of galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption Chronic Myeloid Leukemia Leukemia, Myelogenous, Chronic, BCR-ABL Positive Recently the treatment strategy of Philadelphia chromosome-positive leukemia has undergone groundbreaking changes due to the development of new second-generation cancer-targeting drugs. --- T315I --- --- T315I ---
T315I mutation exhibits strong resistance to both of these cancer-targeting therapies. --- T315I ---
According to the results of the recent studies including the one conducted by our center, it is assumed that imatinib resistance caused by point mutations in patients induces more point mutations and causes selective increase in T315I point mutations during treatment of the second-generation cancer-targeting therapy. --- T315I ---
With regard to peculiar point mutations, V299L, F317L, and E25K/V show relative resistance to dasatinib, and p-loop mutations including G250E, Q252H, Y253F/H and E255K/V and F359C/V show relative resistance to nilotinib. --- V299L ---
With regard to peculiar point mutations, V299L, F317L, and E25K/V show relative resistance to dasatinib, and p-loop mutations including G250E, Q252H, Y253F/H and E255K/V and F359C/V show relative resistance to nilotinib. --- V299L --- --- F317L --- --- E25K --- --- G250E --- --- Q252H --- --- Y253F ---