SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03952052

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Detection by Digital PCR and Next Generation Sequencing of Recurrent Mutations in Waldenström's Disease and Study of Their Distribution in the Different Biological Compartments

Waldenström's disease (WM) is a rare, low-grade lymphoid hematopathy, accounting for 1 to 2% of malignant hematopathies and mainly affecting the elderly. This disease is characterized by lymphoplasmocyte cells infiltration into the bone marrow and by the production of a monoclonal IgM protein in the serum. This disease is accompanied by clinical manifestations of hepato-splenomegaly, signs of hyperviscosity, peripheral neuropathies and biological signs with the presence of cytopenias and cryoglobulinemia. Some forms present node or splenic involvement. While the asymptomatic form maintains overall survival close to that of the healthy subject, the symptomatic form is subject to frequent relapses and remains incurable. Current recommendations for the diagnosis and monitoring of this disease are based on protein electrophoresis from a blood sample to quantify monoclonal IgM production and a myelogram or bone marrow biopsy showing medullary infiltration by lymphoplasmocytic cells. However, protein electrophoresis is an imprecise examination since it does not quantify tumour B lymphocytes and has limitations, particularly in the case of poorly secreting forms. More than 90% of Waldenström cases have the L265P mutation of the MYD88 gene. Although this mutation is not found only in these diseases, it can help in the diagnosis. Other mutations are also present in this pathology. These mutations can define prognostic factors or possibly make it possible to identify therapeutic targets. The development of new technologies makes it possible, on the one hand, to follow the L265P mutation of MYD88 over time as a marker of response to treatment and, on the other hand, to define these prognostic markers or therapeutic targets. This study will first determine the best method for monitoring the mutation of MYD88. In a second step, the investigators will evaluate the best type of sampling and in particular whether this mutation is present in the blood in order to limit the invasive procedures such as bone marrow sampling can be limited. Finally, the investigators will evaluate the prognostic

NCT03952052 Waldenstrom's Disease
MeSH: Osteochondritis

1 Interventions

Name: Determination of mutation

Description: Recurrent mutation determination by digital PCR and next generation sequencing

Type: Other

Patient enrolled


Primary Outcomes

Description: Comparison of level of MYD88L265P mutationin different biological compartment c.

Measure: Quantification of MYD88 L265P mutation

Time: one year

Secondary Outcomes

Description: Comparison of allelic frequency determined by three different techniques (next generation sequencing, digital PCR and specific allele PCR)

Measure: Allelic frequency of L265P mutation of MYD 88 gene

Time: one year

Description: determination of the kinetics of mutation

Measure: Kinetics of mutation

Time: one year

Purpose: Other

Single Group Assignment


There is one SNP

SNPs


1 L265P

More than 90% of Waldenström cases have the L265P mutation of the MYD88 gene. --- L265P ---

The development of new technologies makes it possible, on the one hand, to follow the L265P mutation of MYD88 over time as a marker of response to treatment and, on the other hand, to define these prognostic markers or therapeutic targets. --- L265P ---

Finally, the investigators will evaluate the prognostic Quantification of MYD88 L265P mutation. --- L265P ---

Comparison of level of MYD88L265P mutationin different biological compartment c.. Allelic frequency of L265P mutation of MYD 88 gene. --- L265P ---

Inclusion Criteria: - Over 18 years of age - recently diagnosed for Waldenström's disease - not yet treated for Waldenström's disease Exclusion Criteria: - Pregnancy or breast feeding - HBV or HBC positive - HIV positive Inclusion Criteria: - Over 18 years of age - recently diagnosed for Waldenström's disease - not yet treated for Waldenström's disease Exclusion Criteria: - Pregnancy or breast feeding - HBV or HBC positive - HIV positive Waldenstrom's Disease Osteochondritis The L265P mutation of MYD88 appears as an early oncogenic event in the occurrence of Waldenström disease and may already be present at the Monoclonal Gammapathy of Undetermined Signification (MGUS) to IgM stage suggesting a continuum between the two stages of the disease. --- L265P ---

Monitoring the L265P mutation of MYD88 as a marker of minimal residual disease therefore appears to be a biomarker of major interest in these diseases. --- L265P ---

Several published studies show the interest of monitoring the L265P mutation of MYD88 in MW in particular by quantification of the mutation by allele-specific PCR. --- L265P ---

The originality of this study is based on the comparison of the quantification of the MYD88 L265P mutation in all affected biological compartments (blood, plasma, bone marrow or CD19+ cells) but especially in the monitoring of the mutation at two points of minimal residual disease (mid-treatment and end of treatment). --- L265P ---

One of the parts of the project is the study of the allelic frequency of the L265P mutation of the MYD88 gene in circulating tumor DNA (ctDNA). --- L265P ---

In this study, the allele frequency of the L265P mutation of MYD88 will be compared . --- L265P ---



HPO Nodes