SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03942094

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Efficacy and Safety of Nilotinib as the First-line Treatment for Patients With Newly Diagnosed Chronic-phase Chronic Myeloid Leukemia: a Prospective Study

This is a phase IIIb, multi-centre, single-arm, open-label, prospective study investigating the efficacy and safety of nilotinib as the first-line treatment for the adult patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP) in China. Nilotinib 300 mg BID will be provided in this study. The assessment for the primary efficacy endpoint will be performed at 18 months and the rate of patients obtaining MR4.5 will be measured at this time point. Secondary endpoints include the complete hematologic response(CHR) and the rates of major molecular reactions (MMR) by 3, 6, 9,12,18 and 24 months; event free survival (EFS); overall survival (OS).

NCT03942094 Chronic Myeloid Leukemia, Chronic Phase Nilotinib
MeSH: Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid, Chronic-Phase
HPO: Chronic myelogenous leukemia Leukemia Myeloid leukemia

1 Interventions

Name: Nilotinib

Description: Nilotinib (Tasigna ®), capsules of 150 mg Nilotinib 2 capsules of 150 mg, orally, twice daily

Type: Drug

Nilotinib


Primary Outcomes

Measure: Molecular response (MR) 4.5 at 18 months of nilotinib 300 mg twice a day

Time: 18 months

Secondary Outcomes

Measure: Molecular Response 4.5 at 3, 6, 9, 12, 24 months of nilotinib

Time: 24 months

Measure: Major Molecular Response at 3, 6, 9, 12, 24 months of nilotinib

Time: 24 months

Measure: Rate of CCyR (complete cytogenetic responses: bone marrow Philadelphie positive at 0 % on at least 20 metaphases) at 3, 6, 9, 12, 24 months of nilotinib.

Time: 24 months

Description: Survival since randomization without any event defined as loss of CHR, loss of PCyR or CCyR, death from any cause, progression towards accelerated phase or blast crisis.

Measure: Event-free survival

Time: 24 months

Description: Survival without death from any cause

Measure: Overall survival

Time: 24 months

Purpose: Treatment

Single Group Assignment


There is one SNP

SNPs


1 T315I

Inclusion Criteria: - Male and female patients - Newly diagnosed CP-CML within 6 months prior to study entry, positive Philadelphia chromosome or positive BCR-ABL (M-bcr transcript) - Age ≥ 18 years old (no upper age limit given) - CML-CP defined by primordial cells in peripheral blood or bone marrow <20%, basophils in peripheral blood <20%, platelets ≥100 x 109/L(≥100,000/mm3), except for hepatosplenomegaly - Patient for whom treatment with Imatinib within 2 weeks is expected No other CML treatment except for hydroxyurea and/or anagrelide and/or IFN ECOG score 0 to 2 - Organ function defined by total serum bilirubin levels < 1.5 × the upper limit of the normal range (ULN), SGOT and SGPT < 2.5 UNL, creatinine < 1.5 × ULN, amylase and lipase ≤ 1.5 × ULN and alkaline phosphatase ≤ 2.5 × ULN not directly related to the CML - Laboratory values defined by potassium ≥ LLN, magnesium ≥ LLN, phosphate ≥ LLN, total calcium (correction for serum albumin) ≥ LLN - No planned allogeneic stem cell transplantation - Signed informed consent Exclusion Criteria: - Patients confirmed to have a T315I mutation - TKIs are not allowed to be treated prior to entering the study, unless the patient has an emergency pending the start of the study, and any dose of commercial imatinib may be used to the patient, but no more than 2 weeks - Treatment with IFN for more than 3 mouths - Impaired cardiac function including any of the following: 1. Complete left bundle branch block 2. Right bundle branch block plus left anterior hemiblock,bifascicular block 3. Use of a ventricular-paced pacemaker 4. Congenital long QT syndrome 5. Clinically significant ventricular or atrial tachyarrhythmias 6. Clinically significant resting bradycardia (<50 beats per minute) 7. QTcF >450 msec on screening ECG.If QTcF >450 msec and electrolytes are not within normal ranges before nilotinib dosing, electrolytes should be corrected and then the patient rescreened for QTcF criterion 8. Myocardial infarction within 12 months prior to starting nilotinib 9. Other clinical significant heart disease (e.g. --- T315I ---

uncontrolled diabetes, active or uncontrolled infections) - Congenital or acquired bleeding tendency - Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy - Received other study medications within 30 days (defined as drugs that cannot be used based on approved indications) - Patients unwilling or unable to comply with the protocol - Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention - Concomitant medications known to be strong inducers or inhibitors of the CYP450 Isoenzyme CYP3A4 (for example, erythromycin, ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir, and midazolam) - Impaired gastrointestinal function or disease that may alter the absorption of study drug (e.g.ulcerative disease,uncontrolled nausea,vomiting and diarrhea,malabsorption syndrome,small bowel resection or gastric by-pass surgery) - History of acute pancreatitis within 12 months or chronic pancreatitis - History of acute or chronic diseases of Liver, pancreas or kidney - Concomitant medications with potential QT prolongation - Patients who are pregnant or breast feeding or women of reproductive potential not employing an effective method of birth control.Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to administration of nilotinib.Post menopausal women must be amenorrheic for at least 12 months in order to be considered of non-childbearing potential.Female patients 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 Inclusion Criteria: - Male and female patients - Newly diagnosed CP-CML within 6 months prior to study entry, positive Philadelphia chromosome or positive BCR-ABL (M-bcr transcript) - Age ≥ 18 years old (no upper age limit given) - CML-CP defined by primordial cells in peripheral blood or bone marrow <20%, basophils in peripheral blood <20%, platelets ≥100 x 109/L(≥100,000/mm3), except for hepatosplenomegaly - Patient for whom treatment with Imatinib within 2 weeks is expected No other CML treatment except for hydroxyurea and/or anagrelide and/or IFN ECOG score 0 to 2 - Organ function defined by total serum bilirubin levels < 1.5 × the upper limit of the normal range (ULN), SGOT and SGPT < 2.5 UNL, creatinine < 1.5 × ULN, amylase and lipase ≤ 1.5 × ULN and alkaline phosphatase ≤ 2.5 × ULN not directly related to the CML - Laboratory values defined by potassium ≥ LLN, magnesium ≥ LLN, phosphate ≥ LLN, total calcium (correction for serum albumin) ≥ LLN - No planned allogeneic stem cell transplantation - Signed informed consent Exclusion Criteria: - Patients confirmed to have a T315I mutation - TKIs are not allowed to be treated prior to entering the study, unless the patient has an emergency pending the start of the study, and any dose of commercial imatinib may be used to the patient, but no more than 2 weeks - Treatment with IFN for more than 3 mouths - Impaired cardiac function including any of the following: 1. Complete left bundle branch block 2. Right bundle branch block plus left anterior hemiblock,bifascicular block 3. Use of a ventricular-paced pacemaker 4. Congenital long QT syndrome 5. Clinically significant ventricular or atrial tachyarrhythmias 6. Clinically significant resting bradycardia (<50 beats per minute) 7. QTcF >450 msec on screening ECG.If QTcF >450 msec and electrolytes are not within normal ranges before nilotinib dosing, electrolytes should be corrected and then the patient rescreened for QTcF criterion 8. Myocardial infarction within 12 months prior to starting nilotinib 9. Other clinical significant heart disease (e.g. --- 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
Myeloid leukemia
Genes 12
GATA2 F13A1 CBL ARHGAP26 F13B KRAS PTPN11 SAMD9L KIT SETBP1 NF1 NRAS