SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT02815137

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Prevalence, Kinetic and Prognostic Value of XPO1 E571K Mutation Detection in Plasma Cell-free DNA From Patients Xith Classical Hodgkin Lymphoma

The purpose of this study is to determine if the XPO1 E571K mutation could be used as molecular residual disease biomarker in classical Hodgkin's lymphoma. To determine the interest of the mutation assessment by digital Polymerase Chain Reaction, sensitivity and specificity after 2 courses of chemotherapy (C2) will be compared with the deltaSUVmax determined by Positron Emission Tomography after C2 and at end of treatment.

NCT02815137 Classical Hodgkin Lymphoma
MeSH: Lymphoma Hodgkin Disease
HPO: Hodgkin lymphoma Lymphoma

1 Interventions

Name: Digital Polymerase Chain Reaction

Description: Determination of mutation of XPO1 E571K by digital PCR in blod sample of patient with classical hodgkin lymphoma

Type: Other

XPO1 E571K mutation detection


Primary Outcomes

Description: Comparison of the sensitivity and specificity of the detection of the mutation between delta Standard Uptake Value max (SUV max) determined by PET after two courses of chemotherapy

Measure: If the mutation can be used as a molecular minimal residual disease biomarker

Time: 56 days

Secondary Outcomes

Description: difference between the variant allele fraction at the end of treatment and at the diagnosis

Measure: Kinetic of allele frequency decrease

Time: 224 days

Description: Difference of metabolic parameter in TEP between the end of treatment and the diagnosis

Measure: Variation of Deauville scale

Time: 224 days

Description: Time between the inclusion and the date of progression or death

Measure: Progression-free survival

Time: 2 years

Purpose: Other

Single Group Assignment


There is one SNP

SNPs


1 E571K

Prevalence, Kinetic and Prognostic Value of XPO1 E571K Mutation Detection in Plasma Cell-free DNA From Patients Xith Classical Hodgkin Lymphoma. --- E571K ---

Detection and Prognostic Value of Recurrent XPO1 Mutations of Patients With Classical Hodgkin Lymphoma The purpose of this study is to determine if the XPO1 E571K mutation could be used as molecular residual disease biomarker in classical Hodgkin's lymphoma. --- E571K ---

Inclusion Criteria: - Age ≥18 years - Pathologically confirmed, recent diagnosis of classical Hodgkin Lymphoma - treatment planned with Adriamycin Bleamycin Vinblastine Dacarbazine (ABVD) or Bleomycin Etoposide Adriamycin Cyclophosphamide Vincristine Procarbazine Prednisone (BEACOPP) regimen (and radiotherapy if applicable) - all stages (Ann Arbor I - IV) - Written informed consent - Patient affiliated or beneficiary of a benefit system - untreated patient (no corticosteroids or chemotherapy) Exclusion Criteria: - No informed consent - Treatment by ABVD or BEACOPP not indicated - Previously treated Hodgkin lymphoma (including corticosteroids) - Patients who are pregnant or lactating - Active Hepatitis B or Hepatitis C infection - Known human immunodeficiency virus (HIV) infection - Patient with no social protection - Patient under tutorship or curatorship - Patient not affiliated of beneficiary of a benefit system - Medical contraindication to PET/CT Inclusion Criteria: - Age ≥18 years - Pathologically confirmed, recent diagnosis of classical Hodgkin Lymphoma - treatment planned with Adriamycin Bleamycin Vinblastine Dacarbazine (ABVD) or Bleomycin Etoposide Adriamycin Cyclophosphamide Vincristine Procarbazine Prednisone (BEACOPP) regimen (and radiotherapy if applicable) - all stages (Ann Arbor I - IV) - Written informed consent - Patient affiliated or beneficiary of a benefit system - untreated patient (no corticosteroids or chemotherapy) Exclusion Criteria: - No informed consent - Treatment by ABVD or BEACOPP not indicated - Previously treated Hodgkin lymphoma (including corticosteroids) - Patients who are pregnant or lactating - Active Hepatitis B or Hepatitis C infection - Known human immunodeficiency virus (HIV) infection - Patient with no social protection - Patient under tutorship or curatorship - Patient not affiliated of beneficiary of a benefit system - Medical contraindication to PET/CT Classical Hodgkin Lymphoma Lymphoma Hodgkin Disease A research team of Centre Henri Becquerel recently detected an unexpected recurrent point mutation of XPO1 (exportin 1) (also known as Chromosome Region Maintenance 1) located in exon 15 (c.1711G>A) leading to the Glu571Lys (p.E571K) missense substitution in relapsed/refractory (R/R) Primary Mediastinal Large B-cell Lymphoma (PMBL) patients included in the LYSA LNH03 trial program and in classical Hodgkin's Lymphoma patients. --- Glu571Lys ---

It was found recurrent XPO1 E571K mutations in a large cohort of 94 patients with classical Hodgkin's lymphoma. --- E571K ---

In total, 24.2 % of the patients with classical Hodgkin's lymphoma harbored the XPO1 E571K mutation. --- E571K ---

The research team of the Centre Henri Becquerel have identified a trend toward unfavorable prognostic impact in terms of progression-free survival in patients with detectable XPO1 E571K mutation in plasma cell-free DNA at the end of treatment, which could prove to be statistically significant in a larger cohort. --- E571K ---



HPO Nodes


HPO:
Hodgkin lymphoma
Genes 12
POLE FAS FASLG AAGAB ATM DKC1 CASP10 PRKCD RASGRP1 TCF4 COL14A1 RNF43
Lymphoma
Genes 94
BLM MYC CDKN2A KRAS MYD88 RMRP RAG1 RAG2 MALT1 MSH6 RASGRP1 LIG4 TCF4 PMS2 ICOS NRAS WAS WIPF1 CD19 MS4A1 USB1 IGH TINF2 RB1 DCLRE1C TNFSF12 RTEL1 CTC1 CD27 CD28 PIK3R1 PRF1 NTHL1 TP63 POLE HLA-DRB1 NFKB1 NFKB2 RECQL4 RAD54B CHEK2 TNFRSF13C APC MLH1 TNFRSF13B DKC1 BIRC3 XIAP CASP10 NBN PRKCD COL14A1 FOXP1 CD81 PARN NOP10 CCND1 BCL10 BCL2 MSH2 CHD7 CTLA4 ATM BCL6 MAGT1 RUNX1 TNFRSF1B XRCC4 WRAP53 PTEN MDM2 FAS NHP2 ADA FASLG CR2 SH2D1A TERC AAGAB KIT TERT NSUN2 IL2RG LYST RNF43 ZAP70 DNASE1L3 TP53 RAD54L ITK STAT3 IL7R KIF11 PNP