A Swiss Assessment of Hypothalamic-pituitary-adrenal Axis Suppression After Glucocorticoid Therapy for Leukemia and Lymphoblastic Lymphoma in Children (LeukemiaCort)

A Swiss Prospective Multicenter Longitudinal Assessment of Hypothalamic-pituitary-adrenal Axis Suppression After Glucocorticoid Therapy for Leukemia and Lymphoblastic Lymphoma in Children: An Explorative Study

Plain Language Summary:

Background Glucocorticoids are stress hormones produced by the human body to control inflammation and regulate the immune system. Cortisol is the most well-known example of a glucocorticoid. These stress hormones are essential for the bodys healthy functioning.

To treat certain types of cancer, such as leukemia (blood cancer) in children, glucocorticoids are administered as medications in large quantities. This helps rapidly reduce the number of cancer cells in the body but also leads to the suppression of the body's natural glucocorticoid production, causing a deficiency.

This deficiency can be particularly dangerous for children with leukemia, as their immune defenses are already weakened by chemotherapy, leading to an increased risk of infections. Moreover, the signs of glucocorticoid deficiency in children with leukemia are often indistinguishable from the side effects of chemotherapy, making the deficiency harder to detect.

Objectives The aim of the study is to understand how frequently and for how long the body's natural glucocorticoid production is impaired in children treated for lymphoblastic leukemia and lymphoblastic lymphoma. Additionally, the goal is to identify which children are at particularly high risk.

By gaining a better understanding, this study may help to improve the detection and treatment of glucocorticoid deficiency in children with blood cancer.

Methods Regular low-dose ACTH tests will be conducted to assess the bodys natural glucocorticoid production during and after treatment. To avoid placing additional burden on children who are already heavily affected by the disease, these tests will only be performed when there is already a venous access established and the children are in the hospital for treatment reasons.

Study Overview

• Status: Recruiting
• Conditions: Adrenal Insufficiency; Lymphoma, Lymphoblastic; Leukemia, Lymphoblastic, Acute, Pediatric

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

Study Locations

• Switzerland
  • Aarau, Switzerland
    • Recruiting
    • KSA
    • Contact: Pascal Gächter, Physician; Phone Number: +41 704 22 80; Email: pascal.gaechter@ukbb.ch
  • Basel, Switzerland
    • Recruiting
    • UKBB
    • Contact: Pascal Gächter, Physician; Phone Number: +41 704 22 80; Email: pascal.gaechter@ukbb.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Children aged 0-17 years who are:

Diagnosed with ALL or LBL, and who are treated for at least 21 sequential days with glucocorticoids between the 01.07.2024 and the 30.06.2027 at the Childrens University Hospital of Basel or at the Childrens Hospital of Aarau

Description

Inclusion Criteria:

• diagnosed with ALL or LBL
• treated for at least 21 sequential days with glucocorticoids between the 01.07.2024 and the 30.06.2027 at the Childrens University Hospital of Basel or at the Childrens Hospital of Aarau
• lnformed consent can be obtained from the patient's legal representatives (and the patient if at least 14 years of age) within week 2 of treatment with glucocorticoids

Exclusion Criteria:

- Contraindication to the administration of intravenous synthetical ACTH (Synacthen®): extremely rare cases of known or suspected hypersensitivity to Synacthen®.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Observed Cohort

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurence of Adrenal Insufficiency	The primary outcome of this study is he measurement of the occurrence of HPA axis suppression. The outcome is binary (yes/no) and is considered yes, if a HPA axis suppression occurs at 1 test or more. HPA axis suppression is commonly defined as stimulated cortisol levels below 500nmol/l (below 18μg/dl) in the low-dose ACTH stimulation test, i.e. a measurement of cortisol 30 minutes and 60 minutes after the stimulation with 1 μg of synthetical ACTH (Synacthen®). For further analyses the following subgroups may be considered: - Morning cortisol according to current norm values from our laboratory: suppressed if below 66nmol/l (1-11 years) / below 100nmol/l (12-18 years); Stimulated peak cortisol 300-500nmol/l = partially suppressed; below 300nmol/l = suppressed; Increment of cortisol after stimulation (basal to peak): below 100nmol/l = suppressed, 100-200nmol/l = partially suppressed, above 200nmol/l = normal	Study enrollment until 3 months after the last dose of glucocorticoid treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Adrenal Insufficiency	The measurement of the duration of HPA axis suppression. The outcome is continuous (in weeks). lf there is no occurrence of HPA axis suppression (primary outcome, then this secondary outcome is 0 weeks. The cut-off values are specified under the primary outcome section.	Study enrollment until 3 months after the last dose of glucocorticoid treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of infections	Number of infections: According to medical record. An infection is suspected at a temperature of at least 38.5°C (measured in hospital). This is a continuous outcome (in numbers).	Study enrollment until 3 months after the last dose of glucocorticoid treatment
Total days of hospitalization	Days of hospitalization: This is a continuous outcome (in numbers)	Study enrollment until 3 months after the last dose of glucocorticoid treatment
Total dose of glucocorticoid substitution	Total dose of glucocorticoid substitution: As decided by the treating physician. This is a continuous outcome (hydrocortisone in mg/m2/d)	Study enrollment until 3 months after the last dose of glucocorticoid treatment
Number of ICU admissions	Number of ICU admissions. This is a continuous outcome (in numbers).	Study enrollment until 3 months after the last dose of glucocorticoid treatment

Collaborators and Investigators

• Sponsor: University Children's Hospital Basel
• Collaborators: Gottfried und Julia Bangerter- Rhyner-Stiftung, Basel

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: February 24, 2025
• First Submitted That Met QC Criteria: March 5, 2025
• First Posted (Actual): March 6, 2025

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: pediatric; childhood; leukemia; glucocorticoid; leukaemia; paediatric; Adrenal insufficiency
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Adrenal Gland Diseases; Leukemia, Lymphoid; Hemic and Lymphatic Diseases; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Adrenal Insufficiency
• Other Study ID Numbers: 2024-00736

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: not specified in approval by ethics comittee