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

Study Overview
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Brief Summary
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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.

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

Conditions
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Patients Who Underwent Allograft

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 20 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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What is the study measuring?
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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 |