SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT01456676

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

A Single-arm Dose-finding Phase Ib Multicenter Study of the Oral Smoothened Antagonist LDE225 in Combination With Nilotinib in Chronic or Accelerated Phase of Chronic Myeloid Leukemia Patients Who Have Failed Prior Therapy With Other BCR-ABL Tyrosine-kinase Inhibitors

The purpose of this study is to determine the feasibility of administering the combination of nilotinib and LDE225 to patients with chronic or accelerated phase of chronic myeloid leukemia and to establish the maximum tolerated dose (MTD) and/or recommended Phase II dose level (RP2D) of LDE225 in combination with nilotinib.

NCT01456676 Philadelphia Chromosome Positive Chronic Myelogenous Leukemia
MeSH: Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Philadelphia Chromosome
HPO: Chronic myelogenous leukemia Leukemia Myeloid leukemia

1 Interventions

Name: Nilotinib + LDE225

Description: Nilotinib is an aminopyrimidine ATP-competitive inhibitor of the protein tyrosine kinaseactivity of BCR-ABL.

Type: Drug

Nilotinib + LDE225


Primary Outcomes

Description: Determination of the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of nilotinib in combination with LDE225

Measure: Incidence rate and category of dose limiting toxicities (DLTs) during the first two cycles of therapy

Time: 56 days (2 treatment cycles at 28 days each)

Secondary Outcomes

Description: Assessment of the safety and tolerability profile of nilotinib in combination with LDE225

Measure: No of participants with Adverse drug reactions and serious adverse drug reactions, changes in hematology and blood chemistry values, assessments of physical examinations, vital signs and electrocardiograms

Time: 336 days (12 treatment cycles)

Description: Assessment of the PK characteristics of nilotinib administered in combination with LDE225

Measure: Plasma concentration and basic pharmacokinetics (PK) parameters (as Cmax, Tmax, AUC)

Time: 50 days

Description: Determination of the kinetics of major molecular response

Measure: Major molecular response (MMR) rates at 3, 6 and 12 months

Time: 336 days (12 treatment cycles)

Description: Determination of the kinetics of complete molecular response

Measure: Complete molecular response (CMR) rates at 3, 6 and 12 months

Time: 336 days (12 treatment cycles)

Description: Determination of major cytogenetic response rates

Measure: Major cytogenic response (MCyR) rates by 3, 6 and 12 months

Time: 336 days (12 treatment cycles)

Description: Determination of complete cytogenetic response rates

Measure: Complete cytogenic response (CCyR) rates by 3, 6 and 12 months

Time: 336 days (12 treatment cycles)

Purpose: Treatment

Single Group Assignment


There are 4 SNPs

SNPs


1 E255K

Previously documented BCR-ABL Y253H, E255K/V, T315I or F359C/V mutation Other protocol-defined inclusion/exclusion criteria may apply. --- Y253H --- --- E255K ---


2 F359C

Previously documented BCR-ABL Y253H, E255K/V, T315I or F359C/V mutation Other protocol-defined inclusion/exclusion criteria may apply. --- Y253H --- --- E255K --- --- T315I --- --- F359C ---


3 T315I

Previously documented BCR-ABL Y253H, E255K/V, T315I or F359C/V mutation Other protocol-defined inclusion/exclusion criteria may apply. --- Y253H --- --- E255K --- --- T315I ---


4 Y253H

Previously documented BCR-ABL Y253H, E255K/V, T315I or F359C/V mutation Other protocol-defined inclusion/exclusion criteria may apply. --- Y253H ---



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