Infliximab Efficacy, TDM and Serum TNFα Levels in Pediatric HSCT Recipients With aGVHD: Prospective Observational Study

NCT05362630 | Completed

• 1 other identifier: 441/2022
• Study Type: observational
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

In children receiving a hematopoietic stem cell transplant (HSCT), blood levels of TNFalpha (an inflammatory cytokine) at the onset of the acute GVHD (graft-versus-host disease) could be correlated with the severity of the disease. The hypothesis is that the highest infliximab (a biologic drug against TNFalpha) could be associated with a significant reduction in TNFa levels and, subsequently, with a faster remission of the symptoms and prevention of disease progression. Moreover, a rapid drop of infliximab serum concentration, documented by therapeutic drug monitoring (TDM), could be related to the active phase of GVHD and higher production of TNFalpha. Therefore, the study is aimed at investigating whether the drop in infliximab plasma concentrations could be associated with clinical response and production of TNFalpha. HSCT children receiving infliximab to control GVHD are enrolled. Blood samples will be collected during treatment and they serve to measure drug and TNFalpha concentrations. Drug levels are analyzed by a population pharmacokinetic modeling and results are compared with plasma concentrations of TNFalfa and clinical response.

Conditions

Graft Versus Host Disease, Acute; Hematopoietic Stem Cell Transplantation

Keywords

Graft-Versus-Host Disease; Hemopoietic Stem Cell Transplant; Infliximab; Therapeutic Drug Monitoring; Clinical response; Population Pharmacokinetic Analysis

Outcome Measures

Primary Outcomes (1)

• Correlation between TNFalpha and infliximab plasma concentrations at day +56 of treatment

  Correlation analysis between TNFalpha and infliximab plasma concentrations at day +56 of treatment

  Day 56 after the start of infliximab administration

Secondary Outcomes (8)

• Correlation between TNFalpha and infliximab plasma concentrations at day +7 of treatment

  Day +7 after the start of infliximab administration

• Relationship between baseline TNFalpha plasma concentration and aGVHD overall severity

  From day -7 up to day -1 from the start of infliximab administration

• Clinical response to infliximab

  Day +56 of treatment

• Infliximab plasma concentrations according to clinical response

  From day +7 up to day +56 of treatment

• Percentage of transplant-related deaths and infections during follow-up

  From +6 months up to +1 year after treatment

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Children (0-18 years old) who undergo a HSCT and subsequently, develop an acute GVHD and receive infliximab

You may qualify if:

• Allogeneic HSCT recipient;
• Onset of clinical signs of acute skin, gastrointestinal or hepatic GVHD according to the Glucksberg classification;
• At least five days of steroid treatment (minimum 1 mg/kg of methylprednisone or equivalent) for systemic aGVHD without clinical or laboratory signs of response or no steroid treatment for onset of grade I-II hepatic/gastroesophageal/intestinal isolated aGVHD;
• Patients who consent for the off-label use of infliximab and data processing for research purposes based on the institutional model GECO;
• At least one dose of infliximab received during aGVHD management;
• Minimum follow-up after infliximab administration: 6 months

You may not qualify if:

• Follow up \< 6 months.
• Active fungal or bacterial infection with life-threatening clinical condition (shock or respiratory distress that needs mechanical ventilation)

Sponsors & Collaborators

• University of Pisa: lead

Study Sites (1)

IRCCS Burlo Garofolo

Trieste, 37137, Italy

Location

Related Publications (1)

• Maximova N, Nistico D, Riccio G, Maestro A, Barbi E, Faganel Kotnik B, Marcuzzi A, Rimondi E, Di Paolo A. Advantage of First-Line Therapeutic Drug Monitoring-Driven Use of Infliximab for Treating Acute Intestinal and Liver GVHD in Children: A Prospective, Single-Center Study. Cancers (Basel). 2023 Jul 13;15(14):3605. doi: 10.3390/cancers15143605.

  PMID: 37509268 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma samples to quantitate TNFalpha and infliximab concentrations

MeSH Terms

Conditions

Graft vs Host Disease

Condition Hierarchy (Ancestors)

Immune System Diseases

Study Officials

• Natalia Maximova, MD

  IRCCS Burlo Garofolo - Trieste, Italy

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Pharmacology

Study Record Dates

• First Submitted: April 30, 2022
• First Posted: May 5, 2022
• Study Start: April 1, 2022
• Primary Completion: February 28, 2023
• Study Completion: May 31, 2025
• Last Updated: June 5, 2025

Record last verified: 2025-06

Locations

IT (1)