Acute Lymphoblastic Leukaemias (ALL)HEALEDNCT07313878
Evaluation of Acute and Chronic Nephrotoxicity in Acute Lymphatic Leukemia Patients Using Ultrasound Localization Microscopy
A study testing Ultrasound Localization Microscopy (ULM), Blood sample and Urinanalysis in people with Acute Lymphoblastic Leukaemias (ALL) and Long Term Follow-Up, run by University of Erlangen-Nürnberg Medical School at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 to 17 years
- Conditions the study is for
- Acute Lymphoblastic Leukaemias (ALL), Long Term Follow-Up
- What is being tested?
- Ultrasound Localization Microscopy (ULM), Blood sample and Urinanalysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteGermany
- Study dates
- 19 Nov 2025to 30 Nov 2026
- Phase
- Interventional
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 3 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Germany1 site, 1 recruiting
- Recruiting
Department of Pediatrics and Adolescent Medicine
Erlangen, Baveria, 91054
Axel Karow, MD, +49 9131 8533118, axel.karow@uk-erlangen.de
Alexander Dierl, MD, +4991318533118, alexander.dierl@uk-erlangen.de
About this study
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.
Read more
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.
- Being tested
- Ultrasound Localization Microscopy (ULM), Blood sample, Urinanalysis, Renal sonography
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ultrasound Localization Microscopy (ULM)Diagnostic test
Single Examination: ULM of the kidney after application of a contrast medium (SonoVue®, intravenous).
Ultrasound Localization Microscopy (ULM)Diagnostic test
ULM of the kidney after application of a contrast medium (SonoVue®, intravenous) at two different time points:
Timepoint 1: Before initiation of therapy, latest day 50 before 1st high-dose methotrexate or cyclophosphamide.
Timepoint 2: After termination of intensive treatment (after 6-9 months).
Blood sampleDiagnostic 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.
Blood sampleDiagnostic 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 at Timepoint 1 and 2.
UrinanalysisDiagnostic test
Examination of urine for erythrocytes, leukocytes, pH value, nitrite, protein, blood, and electrolytes.
UrinanalysisDiagnostic test
Examination of urine for erythrocytes, leukocytes, pH value, nitrite, protein, blood, and electrolytes at Timepoint 1 and Timepoint 2.
Renal sonographyDiagnostic test
Renal sonography including resistance index (RI), Doppler signal, flow velocity, and others.
Renal sonographyDiagnostic test
Renal sonography including resistance index (RI), Doppler signal, flow velocity, and others at time point 1 and time point 2.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Diagnostic Test: Ultrasound Localization Microscopy (ULM); Diagnostic Test: Blood sample; Diagnostic Test: Urinanalysis; Diagnostic Test: Renal sonography |
What is being measured
The primary outcome is the main question the study is designed to answer.
CEUS Measurement 1
Peak enhancement (PE)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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
Complete blood count with number of red and white blood cells and platelets per µl
Measured: 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
Measurement of proteinuria in mg/l with protein differentiation
Measured: 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
Resistance index (Sonography)
Measured: Measurement of proteinuria with protein differentiation
Flow velocity
Flow velocity in Doppler Signal (Sonography)
Measured: 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
Weigth of the participant in kilograms
Measured: 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
Height
Height of the participant in meters
Measured: 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
BP
Measurement of systolic, diastolic and mean blood pressure in mmHg
Measured: 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
Electrolytes
Concentration of serum electrolytes (Na, K, Cl, Mg, P) in mmol/L.
Measured: 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
Creatinin and urea level
Serum Creatinin and urea level in mg/dl
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jan 2026
- Study start19 Nov 2025
- Primary completion19 Nov 2026 (estimated)
- Study completion30 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Lymphoblastic Leukaemias (ALL)Studies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Erlangen-Nürnberg Medical School
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07313878
- Sponsor's protocol ID
- HEALED-ULM
- Acronym
- HEALED
- Status last verified
- Dec 2025
- First submitted
- 18 Nov 2025
- Last updated
- 2 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The raw, individual and identifiable patient data are protected and are not available due to data privacy laws. Further data sets are planned to be shared.