Skip to main content
OpenTrials
Completed

NCT Number: NCT05825833

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Acute Graft-versus-host Disease

Age range

Up to 18 year

Sex eligibility

All sexes

Study type

Observational

Primary location

IRCCS Burlo Garofolo

Trieste, 34137, Italy

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

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

Treatment and study plan

Primary outcomes

  1. Correlation between TNFα plasmatic concentration and serum infliximab levels

    Time frame: At day 56 after starting infliximab treatment

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

Secondary outcomes

  1. Correlation between TNFα concentration and serum infliximab levels

    Time frame: At day 7 after starting infliximab treatment

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

  2. Association between Baseline TNFα concentration and aGVHD overall severity

    Time frame: Before starting infliximab treatment

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

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

    Time frame: At day 7 after starting infliximab treatment

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

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

    Time frame: At day 14 after starting infliximab treatment

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

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

    Time frame: At day 28 after starting infliximab treatment

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

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

    Time frame: At day 42 after starting infliximab treatment

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

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

    Time frame: At day 56 after starting infliximab treatment

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

  8. Response to infliximab treatment for aGVHD

    Time frame: At day 7 after starting infliximab treatment

    Number of patients who had Complete Response (CR), Partial Response (PR) or Non-Response (NR). Response is defined as complete resolution of GVHD symptoms and normalization of the biochemical parameters of inflammation.

  9. Response to infliximab treatment for aGVHD

    Time frame: At day 14 after starting infliximab treatment

    Number of patients who had Complete Response (CR), Partial Response (PR) or Non-Response (NR). Response is defined as complete resolution of GVHD symptoms and normalization of the biochemical parameters of inflammation.

  10. Response to infliximab treatment for aGVHD

    Time frame: At day 28 after starting infliximab treatment

    Number of patients who had Complete Response (CR), Partial Response (PR) or Non-Response (NR). Response is defined as complete resolution of GVHD symptoms and normalization of the biochemical parameters of inflammation.

  11. Response to infliximab treatment for aGVHD

    Time frame: At day 42 after starting infliximab treatment

    Number of patients who had Complete Response (CR), Partial Response (PR) or Non-Response (NR). Response is defined as complete resolution of GVHD symptoms and normalization of the biochemical parameters of inflammation.

  12. Response to infliximab treatment for aGVHD

    Time frame: At day 56 after starting infliximab treatment

    Number of patients who had Complete Response (CR), Partial Response (PR) or Non-Response (NR). Response is defined as complete resolution of GVHD symptoms and normalization of the biochemical parameters of inflammation.

  13. Infliximab serum concentration in patients with clinical CR, PR, NR.

    Time frame: At day 7 after starting infliximab treatment

    Infliximab concentration will be measured in peripheral blood sample (serum). Response is defined as complete resolution of GVHD symptoms and normalization of the biochemical parameters of inflammation.

  14. Infliximab serum concentration in patients with clinical CR, PR, NR.

    Time frame: At day 14 after starting infliximab treatment

    Infliximab concentration will be measured in peripheral blood sample (serum). Response is defined as complete resolution of GVHD symptoms and normalization of the biochemical parameters of inflammation.

  15. Infliximab serum concentration in patients with clinical CR, PR, NR.

    Time frame: At day 28 after starting infliximab treatment

    Infliximab concentration will be measured in peripheral blood sample (serum). Response is defined as complete resolution of GVHD symptoms and normalization of the biochemical parameters of inflammation.

  16. Infliximab serum concentration in patients with clinical CR, PR, NR.

    Time frame: At day 42 after starting infliximab treatment

    Infliximab concentration will be measured in peripheral blood sample (serum). Response is defined as complete resolution of GVHD symptoms and normalization of the biochemical parameters of inflammation.

  17. Infliximab serum concentration in patients with clinical CR, PR, NR.

    Time frame: At day 56 after starting infliximab treatment

    Infliximab concentration will be measured in peripheral blood sample (serum). Response is defined as complete resolution of GVHD symptoms and normalization of the biochemical parameters of inflammation.

  18. Percentage of infection during follow-up

    Time frame: At 6 months after starting infliximab treatment

    Viral reactivation (Cytomegalovirus and Epstein-Barr virus), bacterial and fungal infection will be evaluated by medical records

  19. Percentage of infection during follow-up

    Time frame: At 12 months after starting infliximab treatment

    Viral reactivation (Cytomegalovirus and Epstein-Barr virus), bacterial and fungal infection will be evaluated by medical records

  20. Percentage of chronic GVHD

    Time frame: At 6 months after starting infliximab treatment

    Evaluated by medical records

  21. Percentage of chronic GVHD

    Time frame: At 12 months after starting infliximab treatment

    Evaluated by medical records

  22. Percentage of relapse

    Time frame: At 6 months after starting infliximab treatment

    Evaluated by medical records

  23. Percentage of relapse

    Time frame: At 12 months after starting infliximab treatment

    Evaluated by medical records

  24. Transplant-related mortality

    Time frame: At 6 months after starting infliximab treatment

    Evaluated by medical records

  25. Overall survival

    Time frame: At 6 months after starting infliximab treatment

    Evaluated by medical records

  26. Transplant-related mortality

    Time frame: At 12 months after starting infliximab treatment

    Evaluated by medical records

  27. Overall survival

    Time frame: At 12 months after starting infliximab treatment

    Evaluated by medical records

Sponsors and collaborators

Lead sponsor

IRCCS Burlo Garofolo

Other

Registry information

Official study title

Infliximab Efficacy in Relation to Therapeutic Drug Monitoring and Serum Tumor Necrosis Factor (TNF)α Levels in Pediatric Hematopoietic Stem Cell Transplant Recipients

Important dates

Study start
2022
Primary completion
2022
Study completion
2022
First posted
Apr 24, 2023
Registry last updated
Apr 24, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.