NCT05825833

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

Completed Last updated 24 April 2023

What this trial tests

trial in Acute Graft-versus-host Disease in 28 participants. Completed in 31 December 2022.

Timeline

10 March 2022

Primary endpoint
31 December 2022

31 December 2022

Quick facts

Lead sponsor	IRCCS Burlo Garofolo
Status	Completed
Study type	OBSERVATIONAL
Enrollment	28
Start date	10 March 2022
Primary completion	31 December 2022
Estimated completion	31 December 2022
Sites	1 location across Italy

Conditions studied

• Acute Graft-versus-host Disease — all drugs for Acute Graft-versus-host Disease →

Sponsor

IRCCS Burlo Garofolo — full company profile →

Who can join

Under 18, any sex, with Acute Graft-versus-host Disease. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.