Evaluation of Acute and Chronic Nephrotoxicity in Acute Lymphatic Leukemia Patients Using Ultrasound Localization Microscopy

NCT07313878 | Recruiting

• 1 other identifier: HEALED-ULM
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

With increasing survival rates in pediatric oncology, reports of long-term side effects persisting decades after treatment are also rising. Clinically evident nephropathies occur in about 5.5% of survivors more than five years after therapy. Chemotherapeutic agents such as ifosfamide, cisplatin, and carboplatin, as well as kidney-directed treatments like radiation, surgery, or stem cell transplantation, increase this risk. Acute kidney injury has also been described in association with cyclophosphamide and high-dose methotrexate, which are used in the treatment of acute lymphoblastic leukemia (ALL). Studies show a high prevalence of albuminuria (around 14.5% of childhood cancer survivors), an early marker of kidney damage, while standard parameters like creatinine often become abnormal only at later stages. Leukemia survivors suffer from vascular late effects caused by persistent endothelial damage triggered by cancer therapies such as anthracyclines, cyclophosphamide, and asparaginase, which increase inflammation and thrombosis risk. These vascular changes may also contribute to kidney injury. ULM is a high-resolution ultrasound technique that uses microbubbles to visualize the microvasculature and resolve dynamic blood flow changes with a resolution beyond the diffraction limit. ULM is independent of kidney or liver function, has been applied in various organs, and was recently used for the first time to visualize glomeruli-the smallest functional units of the kidney-in humans. This method enables early detection of glomerular injury as a consequence of vascular damage, even before albuminuria appears, potentially allowing earlier adaptation of follow-up and initiation of treatment. This pilot project focuses on survivors of ALL, as they are the largest and best studied pediatric cancer patient group also regarding late effects and, therefore, a sufficient number of individuals can be expected for his monocentric approach. Vascular functional impairment of the kidney could be detected at an early stage and the follow-up structures and measures such as the early use of nephroprotective drugs could be adapted.

Conditions

Acute Lymphoblastic Leukaemias (ALL); Long Term Follow-Up

Outcome Measures

Primary Outcomes (12)

• CEUS Measurement 1

  Peak enhancement (PE)

  Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care

• CEUS Measurement 2

  Wash-in area under the curve (WIAUC)

  Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care

• CEUS Measurement 3

  Wash-in perfusion index (WiPI)

  Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care

• CEUS Measurement 4

  Wash-in rate (WIR)

  Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care

• CEUS Measurement 5

  Wash-out under the curve (WoAUC)

  Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care

• CEUS Measurement 6

  Wash-in and wash-out under the curve (WiWoAUC)

  Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care

• CEUS Measurement 7

  Wash-out rate (WoR)

  Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care

• CEUS Measurement 8

  Time to peak (TTP)

  Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care

• CEUS Measurement 9

  Rise time (RT)

  Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care

• CEUS Measurement 10

  Mean transit time (local) (mTTI)

  Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care

• CEUS Measurement 11

  Fall time (FT)

  Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care

• CEUS Measurement 12

  Peak enhancement (PE)

  Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care

Secondary Outcomes (9)

• Blood Count

  Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care

• Urine status

  Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care

• RI

  Measurement of proteinuria with protein differentiation

• Flow velocity

  Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care

• Weigth

  Study arm early therapeutic effects: Baseline before day 50 of the therapy and follow up after completion of intensive chemotherapy Study arm late therapeutic effects: Baseline at a single-time point in oncological follow-up care

Study Arms (2)

Early therapeutic effects

EXPERIMENTAL

* Diagnosed acute lymphatic leukemia * Treatment day \< 50 according to therapy protocol / no administration of CPM before first examination * From 3 years to \< 18 years

Diagnostic Test: Ultrasound Localization Microscopy (ULM); Diagnostic Test: Blood sample; Diagnostic Test: Urinanalysis; Diagnostic Test: Renal sonography

Late therapeutic effects

EXPERIMENTAL

* Diagnosed acute lymphatic leukemia * Completed oncological treatment * From 3 years to \< 18 years

Diagnostic Test: Ultrasound Localization Microscopy (ULM); Diagnostic Test: Blood sample; Diagnostic Test: Urinanalysis; Diagnostic Test: Renal sonography

Interventions

Ultrasound Localization Microscopy (ULM) DIAGNOSTIC_TEST

Single Examination: ULM of the kidney after application of a contrast medium (SonoVue®, intravenous).

Early therapeutic effects

Blood sample DIAGNOSTIC_TEST

Blood draw (including BB, Diff, Glucose, Na, K, Cl, Ca, LDH, Crea, Cystatin C, Uric Acid, CRP, Albumin, Ferritin, Total Protein) through venous access.

Early therapeutic effects

Urinanalysis DIAGNOSTIC_TEST

Examination of urine for erythrocytes, leukocytes, pH value, nitrite, protein, blood, and electrolytes.

Early therapeutic effects

Renal sonography DIAGNOSTIC_TEST

Renal sonography including resistance index (RI), Doppler signal, flow velocity, and others.

Early therapeutic effects

Eligibility Criteria

• Age: 3 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Diagnosed acute lymphatic leukemia
• From 3 years to \< 18 years
• completed oncological treatment or treatment day \< 50 according to therapy protocol and no administration of CPM before first examination.

You may not qualify if:

• Known allergic disposition to SonoVue / other contrast agents
• Tattoo in the area of the examination field
• Pregnancy
• Breastfeeding mothers
• Contraindication for the use of Sonovue
• Critical condition
• Known clinically evident renal impairment

Sponsors & Collaborators

• University of Erlangen-Nürnberg Medical School: lead

Study Sites (1)

Department of Pediatrics and Adolescent Medicine

Erlangen, Baveria, 91054, Germany

RECRUITING

MeSH Terms

Interventions

Blood Specimen Collection

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Central Study Contacts

Axel Karow, MD

CONTACT

+4991318533118; axel.karow@uk-erlangen.de

Alexander Dierl, MD

CONTACT

+4991318533118; alexander.dierl@uk-erlangen.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2025
• First Posted: January 2, 2026
• Study Start: November 19, 2025
• Primary Completion (Estimated): November 19, 2026
• Study Completion (Estimated): November 30, 2026
• Last Updated: January 2, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 9 months and ending 36 months following article publication
• Access Criteria: The data sets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request as follows: Individual participant data will not be available Study Protocol and Statistical Analysis Plan will be available The data will be available beginning 9 months and ending 36 months following article publication. The data will be available to researchers who provide a methodologically sound proposal. The data will be available for individual participant data meta-analysis, only. Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in our University's data warehouse but without investigator support other than deposited metadata. Information regarding submitting proposals and accessing data may be found at https://www.uk-erlangen.de. Restrictions may apply due to patient privacy and the General Data Protection Regulation.

Locations

DE (1)