Infliximab Efficacy in Relation to Therapeutic Drug Monitoring and Serum TNFα Levels in Pediatric HSCT

NCT05825833 | Completed

• 1 other identifier: RC 18/22
• Study Type: observational
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

Despite significant progress in overall survival and event-free survival in Pediatric Hematopoietic Stem Cell Transplant (HSCT), therapeutic options for graft-versus-host disease control remain limited, particularly in steroid-refractory patients. Several strategies have been proposed in the last 20 years but so far, the results have been inconclusive, complicated by the small population afflicted, inconsistent treatment schedules, different disease classifications and diagnosis methods. The number of studies concerning pediatric patients are even smaller. First line therapy for acute graft-versus-host disease (aGVHD) is steroid treatment that achieve partial or complete remission of the disease in a variable percentage of cases (40-60%), depending mainly to severity of GVHD and number of organ involvement, with hepatic and gastrointestinal GVHD particularly refractory to steroid treatment. For second line therapy there is no a standardized strategy with a great variety of immunosuppressive treatment without a real superiority of a drug in comparison to another. Steroid refractory acute GVHD is therefore one of the most important challenges in HSCT field. One of the more promising routes, based on published data and clinical experience, is the off-label use of Infliximab, an anti-Tumor Necrosis Factor α drug (already approved for many rheumatologic and autoimmune diseases) administered as a second line treatment in patients with steroid-refractory aGVHD at the standardized dosage of 10 mg/kg, although limited evidence has been published to validate this subscription. Biological pattern that could explain susceptibly of GVHD to infliximab treatment could lie in physiopathology of acute gastrointestinal GVHD that may resemble ulcerative rectocolitis. In this case, relation to Therapeutic Drug Monitoring (TDM) and Tumor Necrosis Factor α (TNFα) levels could be critical in monitoring the efficacy of the drug and need of further doses. Limited published data and clinical experience show that Infliximab may be able to further control symptoms and inflammatory response in a promising percentage of treated patients, although some have no benefit from the treatment. The aim of this study is to analyze the role of TNFα concentration in aGVHD, its levels fluctuation and clinical response of GVHD to Infliximab treatment in steroid-refractory pediatric patients.

Conditions

Acute Graft-versus-host Disease

Keywords

Acute graft-versus-host disease; Infliximab; TNFα; Hematopoietic Stem Cell Transplant

Outcome Measures

Primary Outcomes (1)

• Correlation between TNFα plasmatic concentration and serum infliximab levels

  TNFα levels and infliximab concentration will be measured in peripheral blood sample (serum)

  At day 56 after starting infliximab treatment

Secondary Outcomes (27)

• Correlation between TNFα concentration and serum infliximab levels

  At day 7 after starting infliximab treatment

• Association between Baseline TNFα concentration and aGVHD overall severity

  Before starting infliximab treatment

• Number of patients who achieved a significant drop of TNFα concentration after infliximab treatment

  At day 7 after starting infliximab treatment

• Number of patients who achieved a significant drop of TNFα concentration after infliximab treatment

  At day 14 after starting infliximab treatment

• Number of patients who achieved a significant drop of TNFα concentration after infliximab treatment

  At day 28 after starting infliximab 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

Patients with steroid-refractory aGVHD and treated with infliximab

You may qualify if:

• Age of the patients between 0 and 18;
• 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;
• At least one dose of infliximab received during aGVHD management;
• Minimum follow-up after infliximab administration of 6 months

You may not qualify if:

• Active fungal or bacterial infection with life-threatening clinical condition (shock or respiratory distress needing mechanical ventilation)

Sponsors & Collaborators

• IRCCS Burlo Garofolo: lead

Study Sites (1)

IRCCS Burlo Garofolo

Trieste, 34137, Italy

Location

Study Officials

• Alessandra Maestro, PharmD

  IRCCS materno infantile Burlo Garofolo

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2023
• First Posted: April 24, 2023
• Study Start: March 10, 2022
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: April 24, 2023

Record last verified: 2023-04

Locations

IT (1)