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Detection and Prognostic Value of Recurrent XPO1 Mutations of Patients With Classical Hodgkin Lymphoma (XPO1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02815137
Recruitment Status : Recruiting
First Posted : June 28, 2016
Last Update Posted : July 23, 2018
Information provided by (Responsible Party):
Centre Henri Becquerel

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Classical Hodgkin Lymphoma Other: Digital Polymerase Chain Reaction Not Applicable

Detailed Description:
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. It was found recurrent XPO1 E571K mutations in a large cohort of 94 patients with classical Hodgkin's lymphoma. This observation is new and could add new information on driver events and tumorigenesis in this disease. In total, 24.2 % of the patients with classical Hodgkin's lymphoma harbored the XPO1 E571K mutation. It is remarkable that 29% of all XPO1 mutations were only found in the plasma but not in the tumor because of the well-known tumor cell sparsity in Hodgkin's lymphoma. In this particular disease, highly sensitive techniques like digital Polymerase Chain Reaction and targeted Next-Generation Sequencing are essential to highlight low frequency mutations. 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. It was observed that 57% of patients who ultimately relapsed were positive in the plasma after end of therapy. It remains to be established whether this mutation adds new relevant value as compared to Positron Emission Tomography-scan.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Prevalence, Kinetic and Prognostic Value of XPO1 E571K Mutation Detection in Plasma Cell-free DNA From Patients Xith Classical Hodgkin Lymphoma
Actual Study Start Date : June 1, 2016
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
XPO1 E571K mutation detection
Determination of mutation of XPO1571K in patient with classical hodgkin Lymphoma by digital PCR on blood samples and biopsy
Other: Digital Polymerase Chain Reaction
Determination of mutation of XPO1 E571K by digital PCR in blod sample of patient with classical hodgkin lymphoma

Primary Outcome Measures :
  1. If the mutation can be used as a molecular minimal residual disease biomarker [ Time Frame: 56 days ]
    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

Secondary Outcome Measures :
  1. Kinetic of allele frequency decrease [ Time Frame: 224 days ]
    difference between the variant allele fraction at the end of treatment and at the diagnosis

  2. Variation of Deauville scale [ Time Frame: 224 days ]
    Difference of metabolic parameter in TEP between the end of treatment and the diagnosis

  3. Progression-free survival [ Time Frame: 2 years ]
    Time between the inclusion and the date of progression or death

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02815137

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Contact: Fabrice JARDIN, PUPH +33232082465
Contact: Doriane RICHARD, PhD +33232082985

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Centre Henri Becquerel Recruiting
Rouen, France, 76000
Contact: Fabrice JARDIN, PUPH    +33232082465   
Sponsors and Collaborators
Centre Henri Becquerel
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Principal Investigator: Fabrice JARDIN, PUPH Centre Henri Becquerel

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Responsible Party: Centre Henri Becquerel Identifier: NCT02815137     History of Changes
Other Study ID Numbers: CHB 16.02
First Posted: June 28, 2016    Key Record Dates
Last Update Posted: July 23, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Centre Henri Becquerel:
Digital PCR
Hodgkin Lymphoma

Additional relevant MeSH terms:
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Hodgkin Disease
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases