Evaluation of the Relationship Between Anti-PD-1 Exposure and Tumour VOLUME in Patients Treated for Classical HODgkin's Lymphoma.

Hodgkin Lymphoma Clinical Trial

— REVOLUMHOD  

Official title:

Evaluation of the Relationship Between Anti-PD-1 Exposure and Tumour VOLUME in Patients Treated for Classical HODgkin's Lymphoma.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04621604
• Other study ID #: 35RC17_9804_REVOLUMHOD
• Status: Terminated
• Phase: N/A
• Start date: April 12, 2021
• Est. completion date: October 20, 2023

Study information

• Verified date: October 2023
• Source: Rennes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: October 20, 2023
• Est. primary completion date: January 10, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hodgkin Disease
• Hodgkin Lymphoma
• Lymphoma

Intervention

Other:
• blood samples
Extra blood samples will be collected during chemotherapy administration to analyze pharmacokinetics of the iPD1

Locations

Country	Name	City	State
France	CHU Angers	Angers
France	CHU Dijon	Dijon
France	CHU Nantes	Nantes
France	CH Orléans	Orléans
France	CHU Poitiers	Poitiers
France	CHU Rennes	Rennes
France	CHU Tours	Tours
France	CHBA Vannes	Vannes

Sponsors (1)

Lead Sponsor	Collaborator
Rennes University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pearson's correlation between the initial Tumour Metabolic Total Volume and the area under the curve of iPD-1 .	linear relationship, using Pearson's correlation, between the initial Tumour Metabolic Total Volume and the area under the curve (AUC) of iPD-1 during the first treatment.	1 month
Secondary	Correlation between treatment exposure and initial TMTV for each cycle	Degree of correlation between AUC, peak concentration (Cmax), residual concentration (Cmin) measured at each treatment cycle of the first 3 months, and initial TMTV (tumour Metabolic Total Volume)	3 months
Secondary	Correlation between treatment exposure and TMTV at 3 months for each cycle	Degree of correlation between AUC, peak concentration (Cmax), residual concentration (Cmin) measured at each treatment cycle of the first 3 months, and TMTV (tumour Metabolic Total Volume) at 3 months	3 months
Secondary	Correlation between treatment exposure and response to treatment at 3 months	Degree of correlation between AUC, peak concentration (Cmax), and residual concentration (Cmin) measured at each treatment cycle in the first 3 months, and response to treatment as assessed by PET/CT at 3 months	3 months
Secondary	Correlation between treatment exposure and cell free DNA at 3 months	Degree of correlation between AUC, peak concentration (Cmax), and residual concentration (Cmin) measured at each treatment cycle, and cfDNA quantification at 3 months.	3 months
Secondary	Correlation between treatment exposure and PD-1 after 3 months	Degree of correlation between AUC, peak concentration (Cmax), and residual concentration (Cmin) measured at each treatment cycle of the first 3 months, and the expression of membrane (in the tumour before treatment) and soluble PD-1, PDL-1, and PDL-2 (in plasma before treatment and during the first 3 months of treatment)	3 months
Secondary	Correlation between treatment exposure and tolerance after 3 months	Degree of correlation between anti-PD-1 AUC, Cmax or Cmin of anti-PD-1 at each treatment cycle in the first 3 months, and occurrence of immunological adverse events (irAE) within 3 months of starting treatment	3 months
Secondary	Correlation between treatment exposure and progression-free survival	Degree of correlation between anti-PD-1 AUC, Cmax or Cmin of anti-PD-1 at each treatment cycle in the first 3 months, and progression-free survival	1 year
Secondary	Correlation between treatment exposure and overall survival	Degree of correlation between anti-PD-1 AUC, Cmax or Cmin of anti-PD-1 at each treatment cycle in the first 3 months, and overall survival (OS).	1 year