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

Primary Purpose

Classical Hodgkin Lymphoma

Status
Unknown status
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Digital Polymerase Chain Reaction
Sponsored by
Centre Henri Becquerel
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Classical Hodgkin Lymphoma focused on measuring Digital PCR, classical, Hodgkin Lymphoma, mutation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Centre Henri BecquerelRecruiting

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

XPO1 E571K mutation detection

Arm Description

Determination of mutation of XPO1571K in patient with classical hodgkin Lymphoma by digital PCR on blood samples and biopsy

Outcomes

Primary Outcome Measures

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

Kinetic of allele frequency decrease
difference between the variant allele fraction at the end of treatment and at the diagnosis
Variation of Deauville scale
Difference of metabolic parameter in TEP between the end of treatment and the diagnosis
Progression-free survival
Time between the inclusion and the date of progression or death

Full Information

First Posted
June 13, 2016
Last Updated
July 20, 2018
Sponsor
Centre Henri Becquerel
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1. Study Identification

Unique Protocol Identification Number
NCT02815137
Brief Title
Detection and Prognostic Value of Recurrent XPO1 Mutations of Patients With Classical Hodgkin Lymphoma
Acronym
XPO1
Official Title
Prevalence, Kinetic and Prognostic Value of XPO1 E571K Mutation Detection in Plasma Cell-free DNA From Patients Xith Classical Hodgkin Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
July 2018
Overall Recruitment Status
Unknown status
Study Start Date
June 1, 2016 (Actual)
Primary Completion Date
December 2018 (Anticipated)
Study Completion Date
June 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Henri Becquerel

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Classical Hodgkin Lymphoma
Keywords
Digital PCR, classical, Hodgkin Lymphoma, mutation

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
130 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
XPO1 E571K mutation detection
Arm Type
Other
Arm Description
Determination of mutation of XPO1571K in patient with classical hodgkin Lymphoma by digital PCR on blood samples and biopsy
Intervention Type
Other
Intervention Name(s)
Digital Polymerase Chain Reaction
Intervention Description
Determination of mutation of XPO1 E571K by digital PCR in blod sample of patient with classical hodgkin lymphoma
Primary Outcome Measure Information:
Title
If the mutation can be used as a molecular minimal residual disease biomarker
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
Time Frame
56 days
Secondary Outcome Measure Information:
Title
Kinetic of allele frequency decrease
Description
difference between the variant allele fraction at the end of treatment and at the diagnosis
Time Frame
224 days
Title
Variation of Deauville scale
Description
Difference of metabolic parameter in TEP between the end of treatment and the diagnosis
Time Frame
224 days
Title
Progression-free survival
Description
Time between the inclusion and the date of progression or death
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Fabrice JARDIN, PUPH
Phone
+33232082465
Email
fabrice.jardin@chb.unicancer.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Doriane RICHARD, PhD
Phone
+33232082985
Email
doriane.richard@chb.unicancer.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fabrice JARDIN, PUPH
Organizational Affiliation
Centre Henri Becquerel
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre Henri Becquerel
City
Rouen
ZIP/Postal Code
76000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fabrice JARDIN, PUPH
Phone
+33232082465
Email
fabrice.jardin@chb.unicancer.fr

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32079702
Citation
Camus V, Viennot M, Lequesne J, Viailly PJ, Bohers E, Bessi L, Marcq B, Etancelin P, Dubois S, Picquenot JM, Veresezan EL, Cornic M, Burel L, Loret J, Becker S, Decazes P, Lenain P, Lepretre S, Lemasle E, Lanic H, Menard AL, Contentin N, Tilly H, Stamatoullas A, Jardin F. Targeted genotyping of circulating tumor DNA for classical Hodgkin lymphoma monitoring: a prospective study. Haematologica. 2021 Jan 1;106(1):154-162. doi: 10.3324/haematol.2019.237719.
Results Reference
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Detection and Prognostic Value of Recurrent XPO1 Mutations of Patients With Classical Hodgkin Lymphoma

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