Treatment of Adenovirus Disseminated Infections in Hematopoietic Stem Cell Transplant Patients With Adenovirus Digestive Replication (ADENOCLEAR)

Treatment of Adenovirus Disseminated Infections in Hematopoietic Stem Cell Transplant Patients With Adenovirus Digestive Replication- A Pharmaco-epidemiological Prospective Study

Disseminated Adv infections are associated with high morbidity and mortality in HSCT pediatric patients. The most common source of Adv infection after pediatric HSCT is the host digestive tract where latent Adv are reactivated after engraftment. We have shown in a monocentric study that Adv viral load in stools is a predictive factor of blood infection in children with digestive Adv infections. We assume that an early treatment, with antiviral drugs, such as cidofovir and brincidofovir, may avoid severe Adv infections and diseases and thus that molecular surveillance in stool is a critical factor for the control of Adv reactivations.

The study has two main objectives: (i) confirming the impact of Adv viral load in stools on the occurrence of blood infection based on a multicentric prospective cohort study design; and (ii) determining the prognostic and predictive factors for efficacy and toxicity of antiviral drugs, such as brincidofovir and cidofovir.

Study Overview

• Status: Not yet recruiting
• Conditions: Patients Who Underwent Allograft

• Study Type: Observational
• Enrollment (Anticipated): 400

Contacts and Locations

• Study Contact: Name: Jérôme Le GOFF, MDPhD; Phone Number: 33+1 42499493; Email: jerome.le-goff@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months to 20 years (Child, Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

any patient age above 2 month- and under 20 year- old receiving an allogeneic hematopoietic stem cell transplant

Description

Inclusion Criteria:

• Allogeneic hematopoietic stem cell transplantation from any donor other than full-matched related donor
• Age above 2 months and under 20 years
• Provide written informed consent from the parents (if <18) and child
• Free, informed and written consent, signed by the patient and investigator before any Study examination. If the patient is a minor by child (if possible) and both parents or child and the legal representative in case only one parent is alive

Exclusion Criteria:

• Hematopoietic stem cell transplantation from full-matched related donor
• Females who are pregnant or currently nursing
• Any patient receiving cidofovir, ribavirin or any other anti-viral drug under development given in order to treat or prevent
• Current disease attributed to adenovirus infection
• Lack of affiliation to a social security scheme (as a beneficiary or assignee).Current disease attributed to adenovirus infection

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
rate of Adv blood infection according to levels of Adv DNA in stool samples.	Adv blood infection is defined as plasma Adv DNA level greater than 200 copies per milliliter	100 days
rate of response to antiviral drugs	Success will be defined as undetectable level of DNA of Adv in blood after a maximum of 4 weeks of treatment. After 4 weeks of treatment any detectable level of Adv DNA will be considered as a failure.	100 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adv DNA levels > 5 log10 copies/ml in stool	measured at the end of treatment	100 days
Time required achieving 50% decrease of Adv load and undetectable Adv DNA.		100 days
Time required achieving 90% decrease of Adv load and undetectable Adv DNA.		100 days
Incidence of Adv probable or proven disease	We will use the definitions recommended by ECIL (detailed in Appendix 1).; Digestive infection: positive Adv PCR in stool; Local infection: positive Adv PCR in biopsy material or body fluids other than peripheral blood.; Systemic infection/viremia: positive Adv PCR in peripheral blood.; Probable disease: Adv infection plus corresponding symptoms and signs without histological confirmation.; Proven disease: Adv infection plus corresponding symptoms related to the infection and histological confirmation of Adv in the appropriate location.	100 days
Incidence of diarrhea		100 days
Incidence of acute digestive graft versus host disease (aGvHD)		100 days
Overall survival.		100 days
Incidence of Adv probable or proven disease		100 days
Genotypic analysis of the Adv DNA polymerase		100 days
Detection and quantification of herpesviruses in blood		100 days

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2020
• Primary Completion (Anticipated): March 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: March 22, 2018
• First Submitted That Met QC Criteria: March 27, 2018
• First Posted (Actual): March 29, 2018

Study Record Updates

• Last Update Posted (Actual): February 10, 2020
• Last Update Submitted That Met QC Criteria: February 7, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Adenoviridae Infections
• Other Study ID Numbers: K140902J

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No