Acute Graft-versus-host DiseaseNCT05825833

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

An observational study of Acute Graft-versus-host Disease, run by IRCCS Burlo Garofolo at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages Up to 18 years
Conditions the study is for: Acute Graft-versus-host Disease
How many people: 28 participants
Where: 1 siteItaly
Study dates: 10 Mar 2022to 31 Dec 2022
Phase: Observational
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Up to 18 years
All sexes
No healthy volunteers
Child, Adult

Study population: Patients with steroid-refractory aGVHD and treated with infliximab

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

Italy1 site

IRCCS Burlo Garofolo
Trieste, 34137

Other trials in Italy

About this study

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

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

What is being measured

The primary outcome is the main question the study is designed to answer.

Correlation between TNFα plasmatic concentration and serum infliximab levels
TNFα levels and infliximab concentration will be measured in peripheral blood sample (serum)
Measured: At day 56 after starting infliximab treatment

Secondary outcomes (27)

Correlation between TNFα concentration and serum infliximab levels
TNFα levels and infliximab concentration will be measured in peripheral blood sample (serum)
Measured: At day 7 after starting infliximab treatment
Association between Baseline TNFα concentration and aGVHD overall severity
TNFα levels will be measured in peripheral blood sample (serum)
Measured: Before starting infliximab treatment
Number of patients who achieved a significant drop of TNFα concentration after infliximab treatment
TNFα levels will be measured in peripheral blood sample (serum)
Measured: At day 7 after starting infliximab treatment
Number of patients who achieved a significant drop of TNFα concentration after infliximab treatment
TNFα levels will be measured in peripheral blood sample (serum)
Measured: At day 14 after starting infliximab treatment
Number of patients who achieved a significant drop of TNFα concentration after infliximab treatment
TNFα levels will be measured in peripheral blood sample (serum)
Measured: At day 28 after starting infliximab treatment
Number of patients who achieved a significant drop of TNFα concentration after infliximab treatment
TNFα levels will be measured in peripheral blood sample (serum)
Measured: At day 42 after starting infliximab treatment
Number of patients who achieved a significant drop of TNFα concentration after infliximab treatment
TNFα levels will be measured in peripheral blood sample (serum)
Measured: At day 56 after starting infliximab treatment
Response to infliximab treatment for aGVHD
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.
Measured: At day 7 after starting infliximab treatment
Response to infliximab treatment for aGVHD
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.
Measured: At day 14 after starting infliximab treatment
Response to infliximab treatment for aGVHD
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.
Measured: At day 28 after starting infliximab treatment
Response to infliximab treatment for aGVHD
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.
Measured: At day 42 after starting infliximab treatment
Response to infliximab treatment for aGVHD
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.
Measured: At day 56 after starting infliximab treatment
Infliximab serum concentration in patients with clinical CR, PR, NR.
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.
Measured: At day 7 after starting infliximab treatment
Infliximab serum concentration in patients with clinical CR, PR, NR.
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.
Measured: At day 14 after starting infliximab treatment
Infliximab serum concentration in patients with clinical CR, PR, NR.
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.
Measured: At day 28 after starting infliximab treatment
Infliximab serum concentration in patients with clinical CR, PR, NR.
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.
Measured: At day 42 after starting infliximab treatment
Infliximab serum concentration in patients with clinical CR, PR, NR.
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.
Measured: At day 56 after starting infliximab treatment
Percentage of infection during follow-up
Viral reactivation (Cytomegalovirus and Epstein-Barr virus), bacterial and fungal infection will be evaluated by medical records
Measured: At 6 months after starting infliximab treatment
Percentage of infection during follow-up
Viral reactivation (Cytomegalovirus and Epstein-Barr virus), bacterial and fungal infection will be evaluated by medical records
Measured: At 12 months after starting infliximab treatment
Percentage of chronic GVHD
Evaluated by medical records
Measured: At 6 months after starting infliximab treatment
Percentage of chronic GVHD
Evaluated by medical records
Measured: At 12 months after starting infliximab treatment
Percentage of relapse
Evaluated by medical records
Measured: At 6 months after starting infliximab treatment
Percentage of relapse
Evaluated by medical records
Measured: At 12 months after starting infliximab treatment
Transplant-related mortality
Evaluated by medical records
Measured: At 6 months after starting infliximab treatment
Overall survival
Evaluated by medical records
Measured: At 6 months after starting infliximab treatment
Transplant-related mortality
Evaluated by medical records
Measured: At 12 months after starting infliximab treatment
Overall survival
Evaluated by medical records
Measured: At 12 months after starting infliximab treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

10 Mar 202231 Dec 2022

First posted24 Apr 2023
Study start10 Mar 2022
Primary completion31 Dec 2022
Study completion31 Dec 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Acute Graft-versus-host DiseaseStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Other
Time perspective: Cross-sectional
Enrolment: 28 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05825833
Sponsor's protocol ID: RC 18/22
Status last verified: Apr 2023
First submitted: 29 Mar 2023
Last updated: 24 Apr 2023
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 24 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Infliximab Efficacy in Relation to Therapeutic Drug Monitoring and Serum Tumor Necrosis Factor (TNF)α Levels in Pediatric Hematopoietic Stem Cell Transplant Recipients
ClinicalTrials.gov ID: NCT05825833
Acronym / sponsor ID: RC 18/22
Conditions: Acute Graft-versus-host Disease
Keywords: Acute graft-versus-host disease, Infliximab, TNFα, Hematopoietic Stem Cell Transplant
Study type: Observational
Recruitment status: Completed
Enrolment: 28 participants (actual)
Lead sponsor: IRCCS Burlo GarofoloUniversity, hospital or other
Study start: 10 Mar 2022 (actual)
Primary completion: 31 Dec 2022 (actual)
Study completion: 31 Dec 2022 (actual)
First posted: 24 Apr 2023 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Observational model: Other
Time perspective: Cross-sectional

Who may qualify

Ages: Up to 18 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult
Study population: Patients with steroid-refractory aGVHD and treated with infliximab

Key inclusion criteria (7 listed)

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;

Key exclusion criteria (1 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Primary outcome

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)

27 secondary outcomes

Correlation between TNFα concentration and serum infliximab levels
Time frame: At day 7 after starting infliximab treatment
Association between Baseline TNFα concentration and aGVHD overall severity
Time frame: Before starting infliximab treatment
Number of patients who achieved a significant drop of TNFα concentration after infliximab treatment
Time frame: At day 7 after starting infliximab treatment
Number of patients who achieved a significant drop of TNFα concentration after infliximab treatment
Time frame: At day 14 after starting infliximab treatment
Number of patients who achieved a significant drop of TNFα concentration after infliximab treatment
Time frame: At day 28 after starting infliximab treatment
Number of patients who achieved a significant drop of TNFα concentration after infliximab treatment
Time frame: At day 42 after starting infliximab treatment
Number of patients who achieved a significant drop of TNFα concentration after infliximab treatment
Time frame: At day 56 after starting infliximab treatment
Response to infliximab treatment for aGVHD
Time frame: At day 7 after starting infliximab treatment
Response to infliximab treatment for aGVHD
Time frame: At day 14 after starting infliximab treatment
Response to infliximab treatment for aGVHD
Time frame: At day 28 after starting infliximab treatment
Response to infliximab treatment for aGVHD
Time frame: At day 42 after starting infliximab treatment
Response to infliximab treatment for aGVHD
Time frame: At day 56 after starting infliximab treatment
Infliximab serum concentration in patients with clinical CR, PR, NR.
Time frame: At day 7 after starting infliximab treatment
Infliximab serum concentration in patients with clinical CR, PR, NR.
Time frame: At day 14 after starting infliximab treatment
Infliximab serum concentration in patients with clinical CR, PR, NR.
Time frame: At day 28 after starting infliximab treatment
Infliximab serum concentration in patients with clinical CR, PR, NR.
Time frame: At day 42 after starting infliximab treatment
Infliximab serum concentration in patients with clinical CR, PR, NR.
Time frame: At day 56 after starting infliximab treatment
Percentage of infection during follow-up
Time frame: At 6 months after starting infliximab treatment
Percentage of infection during follow-up
Time frame: At 12 months after starting infliximab treatment
Percentage of chronic GVHD
Time frame: At 6 months after starting infliximab treatment
Percentage of chronic GVHD
Time frame: At 12 months after starting infliximab treatment
Percentage of relapse
Time frame: At 6 months after starting infliximab treatment
Percentage of relapse
Time frame: At 12 months after starting infliximab treatment
Transplant-related mortality
Time frame: At 6 months after starting infliximab treatment
Overall survival
Time frame: At 6 months after starting infliximab treatment
Transplant-related mortality
Time frame: At 12 months after starting infliximab treatment
Overall survival
Time frame: At 12 months after starting infliximab treatment

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2023.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Alessandra Maestro, PharmD principal investigator

IRCCS materno infantile Burlo Garofolo

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Acute Graft-versus-host Disease, run by IRCCS Burlo Garofolo at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Correlation between TNFα plasmatic concentration and serum infliximab levels (time frame: At day 56 after starting infliximab treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05825833.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2023.