SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT00702403

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

A Multicenter Phase I/II Study of the Prophylactic Inhibition of BCR-ABL Tyrosine Kinase by Tasigna ® (Nilotinib) After Hematopoietic Cell Transplantation for Philadelphia Chromosome-Positive Leukemias.

This phase I/II trial is studying the side effects and best way to give nilotinib when given alone or sequentially after imatinib mesylate after donor stem cell transplant in treating patients with acute lymphoblastic leukemia or chronic myelogenous leukemia. Nilotinib and imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

NCT00702403 Accelerated Phase Chronic Myelogenous Leukemia Adult Acute Lymphoblastic Leukemia in Remission Blastic Phase Chronic Myelogenous Leukemia Childhood Acute Lymphoblastic Leukemia in Remission Childhood Chronic Myelogenous Leukemia Chronic Myelogenous Leukemia, BCR-ABL1 Positive Chronic Phase Chronic Myelogenous Leukemia Philadelphia Positive Adult Acute Lymphoblastic Leukemia Philadelphia Positive Childhood Acute Lymphoblastic Leukemia Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Childhood Acute Lymphoblastic Leukemia Relapsing Chronic Myelogenous Leukemia Untreated Adult Acute Lymphoblastic Leukemia Untreated Childhood Acute Lymphoblastic Leukemia
MeSH: Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid, Chronic-Phase Blast Crisis Leukemia, Myeloid, Accelerated Phase
HPO: Chronic myelogenous leukemia Leukemia Lymphoid leukemia Myeloid leukemia

3 Interventions

Name: nilotinib

Description: Given PO

Type: Drug

Treatment (prophylactic inhibition of BCR-ABL tyrosine kinase)

Name: imatinib mesylate

Description: Given PO

Type: Drug

Treatment (prophylactic inhibition of BCR-ABL tyrosine kinase)

Name: pharmacological study

Description: Correlative studies

Type: Other

Treatment (prophylactic inhibition of BCR-ABL tyrosine kinase)


Primary Outcomes

Description: Safety and tolerability of nilotinib therapy in patients with imatinib-sensitive leukemia graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.0. Treatment safety failure is defined for a patient with imatinib sensitive Ph+ leukemia as the inability to be able to deliver at least 400 milligrams per day of nilotinib in adults, and 230 milligrams/m2 per day in children, for at least 85% of the time interval between 81 and 365 days after transplant. The overall study will be considered successful if nilotinib is deliverable to more than 75% of the study participants at this minimum specified dose intensity.

Measure: Number of Participants With Treatment Safety Failure

Time: Up to 365 days post-transplant

Secondary Outcomes

Description: To be considered a treatment efficacy success at 1 year posttransplant, the patient's bone marrow must demonstrate complete hematological remission, absence of Philadelphia chromosomes, and not satisfy any of the criteria for treatment failure (>/= 1% aberrantly expressing marrow blasts by multiparameter flow cytometry, >5% BCR/ABL in marrow by fluorescent in situ hybridization, or >1 log rise in peripheral blood BCR/ABL by quantitative polymerase chain reaction (PCR) since day 80).

Measure: The Proportion of Patients at 1 Year With Treatment Efficacy Success

Time: Up to 1 year

Description: The proportion of study participants alive at 1, 2 and 3 years

Measure: Survival

Time: Up to 3 years

Description: The proportion of study participants alive and without hematologic, cytogenetic or molecular evidence of BCR/ABL-positive leukemia at 1 year

Measure: Patients Alive With Out Relapse

Time: Up to 1 year

Description: The proportion of patients with hematologic, cytogenetic or molecular relapse of BCR/ABL-positive leukemia

Measure: Relapse

Time: 1 and 3 years

Purpose: Treatment

Single Group Assignment


There is one SNP

SNPs


1 T315I

Inclusion Criteria: - Body surface area >= 1 m^2 - Allogeneic HCT - Acute lymphocytic leukemia (ALL) or chronic myelogenous leukemia (CML) characterized by the p190 and/or p210 BCR/ABL gene rearrangement - CML in accelerated phase, blast crisis, or blast crisis remission as defined by World Health Organization (WHO) criteria - CML in chronic phase if patient age =< 17 years or a patient of any age with CML in second chronic phase or beyond - Patients with minimal residual disease (MRD) that is not declining in response to tyrosine kinase inhibitor therapy must be screened for the T315I and other mutations - An appropriately matched related or unrelated donor - Signed informed consent - Patient must have a life expectancy of at least 2 months - Stated willingness of the patient to comply with study procedures and reporting requirements - Creatinine =< 2.0 x upper limit normal (ULN) - Platelets > 20 x 10^9 /L - Serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x ULN, conjugated bilirubin < 3 x ULN - Serum potassium phosphorus, magnesium, and calcium >= lower limit normal (LLN) or correctable with supplements prior to first dose of study drug; calcium levels may be corrected for hypoalbuminemia - Serum amylase and lipase < 1.5 x ULN - Female patients of childbearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing; postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential; male and female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug - Careful rationalization with a view to discontinuing or considering alternatives to any concomitant medications that have potential to prolong the QT interval Exclusion Criteria: - Autologous transplant - Non-myeloablative transplant - Patient age > 17 years with CML in first chronic phase - Aberrant antigen expression on marrow leukemic blasts >= 5% by multidimensional flow cytometric assay immediately before conditioning (CML patients in chronic phase exempt from flow cytometry screening) - Ph+ ALL without complete cytogenetic remission immediately before conditioning - Known T315I mutation - Hypersensitivity to Gleevec or Tasigna - Patients who are Tasigna-resistant or intolerant - Central nervous system (CNS) involvement with leukemia at baseline (pre-imatinib therapy); CML chronic phase (CP), accelerated phase (AP) patients exempt from CNS involvement screening - Female patients who are pregnant, breast-feeding, or of childbearing potential without a negative serum pregnancy test at screening; male or female patients of childbearing potential unwilling to use effective contraceptive precautions throughout the trial; post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential - Life expectancy severely limited by diseases other than leukemia - Myocardial infarction within one year prior to starting nilotinib - Other clinically significant heart disease (e.g. --- T315I ---

Inclusion Criteria: - Body surface area >= 1 m^2 - Allogeneic HCT - Acute lymphocytic leukemia (ALL) or chronic myelogenous leukemia (CML) characterized by the p190 and/or p210 BCR/ABL gene rearrangement - CML in accelerated phase, blast crisis, or blast crisis remission as defined by World Health Organization (WHO) criteria - CML in chronic phase if patient age =< 17 years or a patient of any age with CML in second chronic phase or beyond - Patients with minimal residual disease (MRD) that is not declining in response to tyrosine kinase inhibitor therapy must be screened for the T315I and other mutations - An appropriately matched related or unrelated donor - Signed informed consent - Patient must have a life expectancy of at least 2 months - Stated willingness of the patient to comply with study procedures and reporting requirements - Creatinine =< 2.0 x upper limit normal (ULN) - Platelets > 20 x 10^9 /L - Serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x ULN, conjugated bilirubin < 3 x ULN - Serum potassium phosphorus, magnesium, and calcium >= lower limit normal (LLN) or correctable with supplements prior to first dose of study drug; calcium levels may be corrected for hypoalbuminemia - Serum amylase and lipase < 1.5 x ULN - Female patients of childbearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing; postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential; male and female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug - Careful rationalization with a view to discontinuing or considering alternatives to any concomitant medications that have potential to prolong the QT interval Exclusion Criteria: - Autologous transplant - Non-myeloablative transplant - Patient age > 17 years with CML in first chronic phase - Aberrant antigen expression on marrow leukemic blasts >= 5% by multidimensional flow cytometric assay immediately before conditioning (CML patients in chronic phase exempt from flow cytometry screening) - Ph+ ALL without complete cytogenetic remission immediately before conditioning - Known T315I mutation - Hypersensitivity to Gleevec or Tasigna - Patients who are Tasigna-resistant or intolerant - Central nervous system (CNS) involvement with leukemia at baseline (pre-imatinib therapy); CML chronic phase (CP), accelerated phase (AP) patients exempt from CNS involvement screening - Female patients who are pregnant, breast-feeding, or of childbearing potential without a negative serum pregnancy test at screening; male or female patients of childbearing potential unwilling to use effective contraceptive precautions throughout the trial; post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential - Life expectancy severely limited by diseases other than leukemia - Myocardial infarction within one year prior to starting nilotinib - Other clinically significant heart disease (e.g. --- T315I --- --- T315I ---

congestive heart failure, uncontrolled hypertension, unstable angina) - Absolute neutrophil count (ANC) less than 1500 per microliter at study entry despite the use of filgrastim (G-CSF) - Impaired cardiac function, including any one of the following: - Complete left bundle branch block or bifascicular block (right bundle branch block plus left anterior hemiblock) or use of ventricular-paced pacemaker - Congenital long QT syndrome or a family history of long QT syndrome - History of or presence of significant ventricular or atrial tachyarrhythmias - Clinically significant resting bradycardia (< 50 beats per minute) - Corrected QT interval (QTc) > 450 milliseconds on screening electrocardiogram (ECG); if QTc > 450 and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient rescreened for QTc Inclusion Criteria: - Body surface area >= 1 m^2 - Allogeneic HCT - Acute lymphocytic leukemia (ALL) or chronic myelogenous leukemia (CML) characterized by the p190 and/or p210 BCR/ABL gene rearrangement - CML in accelerated phase, blast crisis, or blast crisis remission as defined by World Health Organization (WHO) criteria - CML in chronic phase if patient age =< 17 years or a patient of any age with CML in second chronic phase or beyond - Patients with minimal residual disease (MRD) that is not declining in response to tyrosine kinase inhibitor therapy must be screened for the T315I and other mutations - An appropriately matched related or unrelated donor - Signed informed consent - Patient must have a life expectancy of at least 2 months - Stated willingness of the patient to comply with study procedures and reporting requirements - Creatinine =< 2.0 x upper limit normal (ULN) - Platelets > 20 x 10^9 /L - Serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x ULN, conjugated bilirubin < 3 x ULN - Serum potassium phosphorus, magnesium, and calcium >= lower limit normal (LLN) or correctable with supplements prior to first dose of study drug; calcium levels may be corrected for hypoalbuminemia - Serum amylase and lipase < 1.5 x ULN - Female patients of childbearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing; postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential; male and female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug - Careful rationalization with a view to discontinuing or considering alternatives to any concomitant medications that have potential to prolong the QT interval Exclusion Criteria: - Autologous transplant - Non-myeloablative transplant - Patient age > 17 years with CML in first chronic phase - Aberrant antigen expression on marrow leukemic blasts >= 5% by multidimensional flow cytometric assay immediately before conditioning (CML patients in chronic phase exempt from flow cytometry screening) - Ph+ ALL without complete cytogenetic remission immediately before conditioning - Known T315I mutation - Hypersensitivity to Gleevec or Tasigna - Patients who are Tasigna-resistant or intolerant - Central nervous system (CNS) involvement with leukemia at baseline (pre-imatinib therapy); CML chronic phase (CP), accelerated phase (AP) patients exempt from CNS involvement screening - Female patients who are pregnant, breast-feeding, or of childbearing potential without a negative serum pregnancy test at screening; male or female patients of childbearing potential unwilling to use effective contraceptive precautions throughout the trial; post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential - Life expectancy severely limited by diseases other than leukemia - Myocardial infarction within one year prior to starting nilotinib - Other clinically significant heart disease (e.g. --- T315I ---

congestive heart failure, uncontrolled hypertension, unstable angina) - Absolute neutrophil count (ANC) less than 1500 per microliter at study entry despite the use of filgrastim (G-CSF) - Impaired cardiac function, including any one of the following: - Complete left bundle branch block or bifascicular block (right bundle branch block plus left anterior hemiblock) or use of ventricular-paced pacemaker - Congenital long QT syndrome or a family history of long QT syndrome - History of or presence of significant ventricular or atrial tachyarrhythmias - Clinically significant resting bradycardia (< 50 beats per minute) - Corrected QT interval (QTc) > 450 milliseconds on screening electrocardiogram (ECG); if QTc > 450 and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient rescreened for QTc Inclusion Criteria: - Body surface area >= 1 m^2 - Allogeneic HCT - Acute lymphocytic leukemia (ALL) or chronic myelogenous leukemia (CML) characterized by the p190 and/or p210 BCR/ABL gene rearrangement - CML in accelerated phase, blast crisis, or blast crisis remission as defined by World Health Organization (WHO) criteria - CML in chronic phase if patient age =< 17 years or a patient of any age with CML in second chronic phase or beyond - Patients with minimal residual disease (MRD) that is not declining in response to tyrosine kinase inhibitor therapy must be screened for the T315I and other mutations - An appropriately matched related or unrelated donor - Signed informed consent - Patient must have a life expectancy of at least 2 months - Stated willingness of the patient to comply with study procedures and reporting requirements - Creatinine =< 2.0 x upper limit normal (ULN) - Platelets > 20 x 10^9 /L - Serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x ULN, conjugated bilirubin < 3 x ULN - Serum potassium phosphorus, magnesium, and calcium >= lower limit normal (LLN) or correctable with supplements prior to first dose of study drug; calcium levels may be corrected for hypoalbuminemia - Serum amylase and lipase < 1.5 x ULN - Female patients of childbearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing; postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential; male and female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug - Careful rationalization with a view to discontinuing or considering alternatives to any concomitant medications that have potential to prolong the QT interval Exclusion Criteria: - Autologous transplant - Non-myeloablative transplant - Patient age > 17 years with CML in first chronic phase - Aberrant antigen expression on marrow leukemic blasts >= 5% by multidimensional flow cytometric assay immediately before conditioning (CML patients in chronic phase exempt from flow cytometry screening) - Ph+ ALL without complete cytogenetic remission immediately before conditioning - Known T315I mutation - Hypersensitivity to Gleevec or Tasigna - Patients who are Tasigna-resistant or intolerant - Central nervous system (CNS) involvement with leukemia at baseline (pre-imatinib therapy); CML chronic phase (CP), accelerated phase (AP) patients exempt from CNS involvement screening - Female patients who are pregnant, breast-feeding, or of childbearing potential without a negative serum pregnancy test at screening; male or female patients of childbearing potential unwilling to use effective contraceptive precautions throughout the trial; post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential - Life expectancy severely limited by diseases other than leukemia - Myocardial infarction within one year prior to starting nilotinib - Other clinically significant heart disease (e.g. --- T315I --- --- 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