Clinical trial NCT04621604: Evaluation of the Relationship Between Anti-PD-1 Exposure and Tumour VOLUME in Patients Treated for Classical HODgkin's Lymphoma.
Official title: Evaluation of the Relationship Between Anti-PD-1 Exposure and Tumour VOLUME in Patients Treated for Classical HODgkin's Lymphoma.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Hodgkin Lymphoma
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
First posted: 2020-11-09
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Anti-PD-1antibodies (iPD-1) are indicated as monotherapy in the treatment of adult patients with classical LH. The recommended dosage in LH is based on solid tumour experience and no dose-concentration-effect studies have been conducted.

According to the literature, therapeutic efficacy appears to be highly variable, and could be related to differences in treatment exposure.

Since Total metabolic tumor volume (TMTV) is a prognostic factor in LH and the clearance of iPD-1, and thus exposure to iPD-1, is related to clinical efficacy, we hypothesize that TMTV influences the exposure to iPD-1 and thus its therapeutic efficacy.

The aim of this study is to evaluate the relationship between TMTV and anti-PD-1 exposure in refractory or relapsed LH.

Detailed description: Anti-PD-1antibodies (iPD-1), nivolumab (NIV) and pembrolizumab (PEM), act by blocking the interaction of the PD-1 receptor with its PDL1/PDL-2 ligands, which are overexpressed by tumour cells and their microenvironment, thus restoring an effective anti-tumour response. NIV and PEM are indicated as monotherapy in the treatment of adult patients with classical LH. They are administered as intravenous infusions on an outpatient basis. The recommended dosage for IVN or EMP in LH is based on solid tumour experience and no dose-concentration-effect studies have been conducted.

According to the literature, therapeutic efficacy appears to be highly variable, and could be related to differences in treatment exposure.

Since Total metabolic tumor volume (TMTV) is a prognostic factor in LH and the clearance of iPD-1, and thus exposure to iPD-1, is related to clinical efficacy, we hypothesize that TMTV influences the exposure to iPD-1 and thus its therapeutic efficacy.

The aim of this study is to evaluate the relationship between TMTV and anti-PD-1 exposure in refractory or relapsed LH. Highlighting such a relationship will make it possible to identify treatment algorithms according to the initial TMTV with a target plasma concentration defined according to the TMTV measurement. New therapeutic biomarkers would thus be highlighted.

This personalised medicine approach would make it possible to maximise the effect while reducing toxicity. This project is a first step in the implementation of a clinical study leading to recommendations for anti-PD-1 dose adaptation based on concentration and TMTV.

Eligibility criteria: Inclusion Criteria:

* Patient at least 18 years of age
* Patient for whom anti-PD-1 antibody therapy (nivolumab or pembrolizumab) is given as monotherapy for relapsed or refractory classical Hodgkin's lymphoma within the scope of the WMA.
* Patient for whom a PET-CT for the evaluation of TMTV is available within 30 days prior to the first treatment without intercurrent antitumour therapy between the last PET-CT and the start of anti-PD1 treatment.
* For women of childbearing age, use of effective contraception
* Patient with free, informed and written consent
* Patient affiliated to a social security scheme

Exclusion Criteria:

* Persons of full age subject to legal protection (judicial protection, guardianship, trusteeship), persons deprived of their liberty, pregnant or breastfeeding women, persons unable to give consent
* Patient with a contraindication to NIV or PEM treatment
* Patient previously treated with anti-PD1 regardless of indication
* Patient treated with anti-PD1 in combination with other anti-tumour treatment
* Patient participating in another interventional clinical study

Primary outcomes:
measure: Pearson's correlation between the initial Tumour Metabolic Total Volume and the area under the curve of iPD-1 .
timeFrame: 1 month
Secondary outcomes:
measure: Correlation between treatment exposure and initial TMTV for each cycle
timeFrame: 3 months
measure: Correlation between treatment exposure and TMTV at 3 months for each cycle
timeFrame: 3 months
measure: Correlation between treatment exposure and response to treatment at 3 months
timeFrame: 3 months
measure: Correlation between treatment exposure and cell free DNA at 3 months
timeFrame: 3 months
measure: Correlation between treatment exposure and PD-1 after 3 months
timeFrame: 3 months
measure: Correlation between treatment exposure and tolerance after 3 months
timeFrame: 3 months
measure: Correlation between treatment exposure and progression-free survival
timeFrame: 1 year
measure: Correlation between treatment exposure and overall survival
timeFrame: 1 year
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU Angers
city: Dijon
country: France
facility: CHU Dijon
city: Nantes
country: France
facility: CHU Nantes
city: Orléans
country: France
facility: CH Orléans
city: Poitiers
country: France
facility: CHU Poitiers
city: Rennes
country: France
facility: CHU Rennes
city: Tours
country: France
facility: CHU Tours
city: Vannes
country: France
facility: CHBA Vannes
Study officials:
affiliation: Rennes University Hospital
name: Roch Houot, Pr
role: PRINCIPAL_INVESTIGATOR
References: