THRILL: Treat Hyperinflammation in child oncology study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Prinses Maxima Centrum voor Kinderoncologie B.V.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Immune System Diseases [C20]

Decision date (initial)

2026-05-18

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

KIKA

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Efficacy

To assess the efficacy of early administration of the recombinant IL-1R antagonist anakinra as adjunctive treatment to standard of care (SoC) in pediatric cancer patients admitted to ICU with sepsis and signs of hyperinflammation on 28-day all-cause mortality compared to a historical cohort receiving standard of care only.

Secondary objectives 6

1. To describe the safety of anakinra
2. To assess the effect of early anakinra on organ dysfunction on day 3 after ICU admission
3. To assess the effect of early anakinra on organ dysfunction on day 7 after ICU admission.
4. To assess the effect of early anakinra on ICU mortality.
5. To assess the effect of early anakinra on the use and duration of critical care support.
6. To assess the effect of early anakinra on the ICU length of stay (LOS).

Conditions and MedDRA coding

Hyperinflammation

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Children and adolescents with an age between eight months and 18 years admitted to ICU.
2. An underlying malignancy (according to ICD-10 code) or post-HCT at time of ICU admission.
3. Admitted to ICU with suspected or confirmed infection.
4. Phoenix Sepsis score total ≥ 2
5. Serum ferritin level ≥ 2000 µg/L at ICU admission, so called Phenotype 1 patients.
6. Written informed consent/assent from patients and/or from parents or legal guardians for minor patients according to local law and regulations.

Exclusion criteria 12

1. Age younger than eight months and/or weight < 10 kg.
2. Sexually active, fertile male patients, not willing to use an effective method of contraception, for the duration of study therapy.
3. Patients are excluded if predefined treatment limitations are in place at the time of ICU admission. Treatment limitations are defined as a do-not-resuscitate (DNR) order or any restriction on the use of mechanical ventilation, vasopressor or inotropic support, continuous renal replacement therapy, or extracorporeal membrane oxygenation (ECMO).
4. Patients for whom informed consent was not obtained.
5. Any prior underlying severe organ toxicity, for example CF patients with severe pulmonary dysfunction, patients with cardiac failure, patients with chronic renal failure, etc. either due to cancer, cancer treatment or prior causes.
6. Treatment with targeted anti-inflammatory therapy for hyperinflammation (biologic or JAK inhibitor) in the week prior to ICU admission.
7. Previous treatment with anakinra in the month prior to the ICU admission.
8. Known hypersensitivity to anakinra or to any of the other ingredients, or to proteins produced by Escherichia coli.
9. Previous treatment with TNF alfa blocking agents (within 5x half-life of the drug).
10. Severe liver dysfunction according to the criteria of the European and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition including biochemical evidence of severe liver injury (no chronic impairment) and coagulopathy not corrected by vitamin K (prothrombin time (PT) ≥15 sec or international normalized ratio (INR) ≥ 1.5 with evidence of hepatic encephalopathy or PT ≥ 20 sec or INR > 2 with or without encephalopathy).
11. Participation in a clinical trial which prohibits participation in another clinical trial with an IMP.
12. Pregnant or lactating patients, or sexually active female patients of childbearing potential not willing to use a highly effective method of contraception for the duration of study therapy and pregnancy testing prior to inclusion.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The difference in 28-day all-cause mortality between the early anakinra + SoC and historical SoC group.

Secondary endpoints 8

1. Adverse events (AEs), as characterized by type, frequency, severity (as graded using CTCAE v5.0)
2. ≥ grade 3 liver enzyme abnormalities (ALT, bilirubin)
3. The cumulative incidence of secondary infections.
4. The difference in cumulative Phoenix-8 organ dysfunction score over three days between the early anakinra + SoC and historical SoC group.
5. The difference in cumulative Phoenix-8 organ dysfunction score over seven days between the early anakinra + SoC and historical SoC group.
6. The difference in ICU mortality between the early anakinra + SoC and historical SoC group.
7. The comparison of the two groups of treatment on: - the number of ventilator-free days at day 28 - the number of vasoactive medication-free days at day 28 - the highest VIS score - the cumulative VIS score over seven days - the requirement of CRRT - the requirement of ECMO
8. The comparison of the two groups of treatment on ICU LOS.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Prinses Maxima Centrum voor Kinderoncologie B.V.

Sponsor organisation

Prinses Maxima Centrum voor Kinderoncologie B.V.

Address

Heidelberglaan 25

City

Utrecht

Postcode

3584 CS

Country

Netherlands

Scientific contact point

Organisation

Prinses Maxima Centrum voor Kinderoncologie B.V.

Contact name

Dr. C. Lindemans

Public contact point

Organisation

Prinses Maxima Centrum voor Kinderoncologie B.V.

Contact name

Dr. C. Lindemans

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications